Journal of Functional Foods 37 (2017) 74–89

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Journal of Functional Foods

journal homepage: www.elsevier.com/locate/jff

Streptococcus thermophilus: From yogurt starter to a new promising

probiotic candidate?
Ophélie Uriot a,b, Sylvain Denis a, Maira Junjua b, Yvonne Roussel b, Annie Dary-Mourot b,⇑,1,
Stéphanie Blanquet-Diot a,1
a
UMR 454 UCA-INRA MEDIS Microbiota, Digestive Environment and Health, Université Clermont Auvergne, 63000 Clermont-Ferrand, France
b
URAFPA, Unité de Recherche Animal et Fonctionnalités des Produits Animaux, Equipe Protéolyse et Biofonctionnalité des Protéines et des Peptides, Université de Lorraine,
54506 Vandoeuvre-les-Nancy, France

a r t i c l e i n f o a b s t r a c t

Article history: Probiotics are defined as live microorganisms that when administered in adequate amount confer a
Received 10 March 2017 health benefit to the host. To be considered as a probiotic, a bacterial strain must not only be safe but
Received in revised form 7 July 2017 should also survive in the human gastrointestinal tract and exert health benefits on its host.
Accepted 18 July 2017
Streptococcus thermophilus is a Gram positive bacterium widely used in dairy fermentations for the
production of yogurt and cheese. In contrast with other lactic acid bacteria, the probiotic status of
S. thermophilus remains still questioned. This review gives an update of the human trials, in vivo assays
Keywords:
in animal models and in vitro experiments, which have assessed the resistance of S. thermophilus to gas-
S. thermophilus
Probiotic
trointestinal stresses and have investigated its positive health effects. The underlying mechanisms of
Gastrointestinal survival action are also described and the probiotic status of the bacterium is debated with respect to the available
Health effects literature.
Ó 2017 Published by Elsevier Ltd.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
2. S. thermophilus: a key LAB in dairy production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3. Survival of S. thermophilus in the digestive environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.1. Human trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.2. In vivo studies in animal models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
3.3. In vitro experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4. Acid and bile resistance mechanisms in S. thermophilus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
5. Beneficial health effects of S. thermophilus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
5.1. Alleviation of lactose intolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
5.2. Prevention of chronic gastritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
5.3. Prevention of diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
6. Possible mechanisms of action of S. thermophilus on the host health. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
6.1. Antimicrobial activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
6.2. Antioxidant activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
6.3. Immunomodulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
6.4. Effect on intestinal barrier function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
6.5. Interactions with intestinal microbiota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

⇑ Corresponding author at: URAFPA, Université de Lorraine, Faculté des Sciences et Techniques, Campus Aiguillettes, 54506 Vandoeuvre-les-Nancy, France.
E-mail address: annie.dary@univ-lorraine.fr (A. Dary-Mourot).
1
Co-senior authors.

http://dx.doi.org/10.1016/j.jff.2017.07.038
1756-4646/Ó 2017 Published by Elsevier Ltd.
 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89 75

1. Introduction health to patients suffering from a form of malnutrition caused by

the consumption of highly refined food (Kollath, 1953). One year
The original hypothesis of the positive role played by certain later, Ferdinand Vergin proposed that probiotics were the opposite
bacteria was first introduced by Élie Metchnikoff, who wrote in of antibiotics (Vergin, 1954). In 1965, the work of Lilly and Still-
1907 that ‘‘A reader who has little knowledge about such matters well (Lilly & Stillwell, 1965) gave a new dimension to the defini-
may be surprised by my recommendation to absorb large quantities tion of probiotics. Observations that some secretions of
of microbes, as a general belief is that microbes are harmful. This Colpidium campylum could increase the growth of Tetrahymena
belief is erroneous. There are many useful microbes, amongst which pyriformis prompted them to define probiotic as ‘‘the secretions
the lactic bacilli have honorable place.” and ‘‘The dependence of the of one microorganism which stimulate the growth of another
intestinal microbes on the food makes it possible to adopt measures microorganism”. Similarly, in 1971, the term probiotics referred
to modify the flora in our bodies and to replace the harmful microbes to tissue extracts capable of stimulating microbial growth
by useful microbes.” (Metchnikoff, 1907). From Metchnikoff till (Sperti, 1971). In 1974, the word probiotic was used for the first
today, the probiotic concept has drastically evolved and different time to describe a microbial feed/food supplement and defined
definitions of probiotics have been proposed (Table 1). For exam- as ‘‘organisms and substances contributing to the intestinal micro-
ple, in 1953, the word ‘‘probiotika” was used by Werner Kollath to bial balance” (Parker, 1974). In 1992, Fuller removed the word
designate organic and inorganic supplements necessary to restore ‘‘substances” from the probiotic’s definition and emphasized on
their viability defining probiotics as ‘‘live microbial feed supple-
ments which beneficially affect the host animal by improving
Table 1
Evolutionary stages of probiotic definitions. Adapted from Vasiljevic and Shah (2008) microbial balance” (Fuller, 1992). Because this definition was not
wide enough to cover the entire indigenous microflora, another
Year Description Sources
definition was proposed by Havenaar and Huis in‘t Veld in 1992
1907 First hypothesis of a positive role for Metchnikoff (1907) (Havenaar & Huis in’t Veld, 1992). In their view, ‘‘probiotics are
certain bacteria
the viable mono- or mixed microbial cultures which when applied
1953 First use of the word ‘‘probiotika” which Kollath (1953)
appoints organic and inorganic to animal or man have beneficial effects on their host by improv-
supplements necessary to restore health ing the properties of indigenous microflora”. In 1996, the cultured
1954 Probiotics are defined as opposite of Vergin (1954) dairy products were also added to the probiotic concept and
antibiotics Schaafsma defined them as ‘‘living microorganisms which when
1955 Probiotics can be effective against the Kolb (1955)
ingested in certain numbers exert health benefits beyond inherent
deleterious effects of antibiotics
1965 Substances secreted by one microorganism Lilly and Stillwell basic nutrition” (Schaafsma, 1996). This definition was confirmed
which stimulate the growth of another one (1965) in 2002 by the Food and Agriculture Organization (FAO) of the
1971 Tissue extracts able to stimulate microbial Sperti (1971) United Nations and World Health Organization working group
growth
(FAO/WHO, 2002) stating that probiotics are ‘‘live microorganisms
1973 Compounds that build resistance to Fujii and Cook (1973)
infections in the host but do not inhibit the
which when administered in adequate amounts, confer a health
growth of microorganisms in vitro benefit on the host”, and reconfirmed by the FAO in 2006. In
1974 Organisms and substances contributing to Parker (1974) 2014, this definition was revised with minor grammatical correc-
microbial balance in the intestine tion by an expert panel of the International Scientific Association
1992 Live microbial feed supplements which Fuller (1992)
for Probiotics and Prebiotics as, ‘‘live microorganisms that, when
beneficially affect the host animal by
improving microbial balance administrated in adequate amounts, confer a health benefit on
1992 Viable mono- or mixed culture of live Havenaar and Huis in’t the host” (Hill et al., 2014). In 2015, a framework was also pro-
microorganisms which, when applied to Veld (1992) posed for the characterization of novel probiotic bacteria and the
animals or mans, have a beneficial effect on
assessment of their safety and efficacy in accordance with Euro-
the host by improving the properties of the
indigenous microflora
pean health policy (Miquel et al., 2015).
1996 Live microbial culture or cultured dairy Salminen (1996) Numerous health benefits resulting from the ingestion of probi-
products which beneficially influence the otics have been observed in animal models and are expected to
health and nutrition of the host occur in humans as well, while others have been specifically
1996 Living microorganisms which, upon Schaafsma (1996)
proved through human trials (Table 2). These health benefits are
ingestion in certain numbers, exert health
benefits beyond inherent basic nutrition mainly associated with the prevention and treatment of diarrhea
1999 Microbial cell preparations or components Salminen, Ouwehand, symptoms, the prevention of irritable bowel diseases, colitis and
of microbial cells that have a beneficial Benno, and Lee (1999) necrotizing enterocolitis and the relief in lactose intolerance (Di
effect on the health and well-being of the
Cerbo, Palmieri, Aponte, Morales-Medina, & Iannitti, 2016; Hill
host
2001 A preparation or a product containing Schrezenmeir and de
et al., 2014; Nagpal et al., 2012; Vasiljevic & Shah, 2008). In addi-
viable, defined microorganisms in Vrese (2001) tion, certain probiotic bacteria have been recommended for the
sufficient numbers, which alter the treatment of extra-intestinal pathologies such as atopic dermatitis,
microflora (by implantation or hypercholesterolemia or allergies (Boyle & Tang, 2006; Di Cerbo
colonization) in a compartment of the host
et al., 2016; Vasiljevic & Shah, 2008). Overall, these health effects
and in this way exert beneficial health
effects on this host are highly strain-dependent and there is not a single probiotic
2002 Live microorganisms which when FAO/WHO (2002) strain which can confer all the benefits previously reported
administered in adequate amounts, confer (Senok, Ismaeel, & Botta, 2005; Shah, 2007). Even if certain mech-
a health benefit on the host anism action of probiotics begin to be well described in the litera-
2014 Grammatical adjustment of the FAO/WHO Hill et al. (2014
definition: live microorganisms that, when
ture, such as the anti-pathogenic activities, which include direct
administered in adequate amounts, confer antagonism, immunomodulation and competitive exclusion
a health benefit on the host (Preidis et al., 2011), they are far from being fully elucidated. How-
2015 List of criteria that should be assessed to Miquel et al. (2015) ever, it is yet known that after their consumption, probiotics may
obtain marketing authorization and health
exert their beneficial effects by influencing the intestinal luminal
claim for probiotic bacteria in accordance
with European health policy environment, the epithelial and mucosal barrier function as well
as the immune system (Nagpal et al., 2012).
76 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89

Table 2
Main bacterial and yeast probiotics and their health effects, as observed in animal models or during human trials.

Effects on health Strains Human Animal References

trials models
Prevention of diarrhea B. bifidum (LMG-P17500) X – Beniwal et al. (2003), Bowen et al. (2007), Canani et al. (2007), Di Cerbo et al.
B. breve (K-110) X X (2016), Korpela et al. (2016), O’Callaghan and van Sinderen (2016), Saavedra et al.
B. infantis (CECT7210) X X (1994), Saavedra et al. (2004), Shah (2007), and Trabelsi, Ktari, Ben Slima, Hamden,
B. lactis (B94; Bb12) X – and Ben Salah (2016)
B. longum (SBT-2828) X X
Lb. acidophilus (CERELA; X X
DSM21007; GP1B; La-5; LMG-
P17549)
Lb. bulgaricus (LMG-P17550) X X
Lb. casei (CERELA; DN-114001; X X
Shirota)
Lb. fermentum (353; KLD) X –
Lb. plantarum (2017405; TN8) X X
Lb. reuteri (DSM-12246; DSM- X –
17938)
Lb. rhamnosus (35; E/N; GG; X X
Oxy; Pen)
S. boulardii (It) X –
S. thermophilus (LMG-P17503) X X
Prevention of B. breve (M-16 V) X – Guandalini et al. (2010), O’Callaghan and van Sinderen (2016), and Shah (2007)
inflammatory bowel B. longum X –
diseases B. infantis X –
Lb. acidophilus X –
Lb. plantarum X X
Lb. casei X –
Lb. bulgaricus X –
S. thermophilus X –
Prevention of gastric B. bifidum X – Di Cerbo et al. (2016), Hauser, Salkic, Vukelic, JajacKnez, and Stimac (2015), Hurduc,
diseases and H. pylori B. breve (Bb99) X – Plesca, Dragomir, Sajin, and Vandenplas (2009), Shah (2007), and Wang and Huang
infections B. lactis (Bb12) X – (2014)
B. longum (HY8001) X –
Lb. acidophilus (HY2177; La5; X –
LB; NAS)
Lb. casei (DG; DN-114001; X –
HY2743, Shirota)
Lb. gasseri (OLL2716) X –
Lb. johnsonii (La1; No1088) X X
Lb. paracasei (F19) X –
Lb. reuteri (ATCC55730; X –
ATCCPTA6475; DSM17938)
Lb. rhamnosus (GG; LC705) X –
P. freundenreichii subsp. X –
shermanii (JS)
S. boulardii X –
S. thermophilus (B-1) X –
Oral health effect Lb. brevis (CD2) X – Campus et al. (2014), Hasslöf, West, Videhult, Brandelius, and Stecksén-Blicks
Lb. paracasei (F19; SD1) X – (2013), Näse et al. (2001), Stensson et al. (2014), Teanpaisan and Piwat (2014)
Lb. reuteri (ATCC55730) X –
Lb. rhamnosus (GG) X –
Alleviation of lactose Lb. bulgaricus X – EFSA (2010)
intolerance S. thermophilus X –
Prevention of respiratory B. lactis (Bi-07) X – Di Cerbo et al. (2016); Guillemard, Tondu, Lacoin, and Schrezenmeir (2010), Leyer,
tract infections Lb. acidophilus (NCFM) X – Li, Mubasher, Reifer, and Ouwehand (2009), and Makino et al. (2010)
Lb. bulgaricus (OLL1073 R-1) X –
Lb. casei (DN-114001) X –
Lb. pentosus (b240) X –
Prevention of urogenital Lb. acidophilus (LA02) X – Di Cerbo et al. (2016)
infections Lb. brevis (CD2) X –
Lb. fermentum (LF10; LF15; X –
LN99; RC-14)
Lb. gasseri (LN40; Lba EB01- X –
DSM 14869)
Lb. plantarum (FV9; LP01; X –
P17630)
Lb. reuteri (CRL1324) X –
Lb. rhamnosus (GR-1; Lbp X –
PB01-DSM 14870; LN113)
Lb. salicinius (FV2) X –
P. acidilactici (LN23) X –
 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89 77

Table 2 (continued)

Effects on health Strains Human Animal References

trials models
Prevention of allergy and B. adolescentis X – Di Cerbo et al. (2016), Giovannini et al. (2007), Koyama et al. (2010), Shah (2007),
dermatitis B. bifidum X – West, Hammarström, and Hernell (2009)
B. breve (BR03) X –
Lb. acidophilus (L-92) X –
Lb. casei (DN-114001; Shirota) X –
Lb. gasseri (SBT0270;SBT0274) – X
Lb. paracasei (F19; LP-33) X –
Lb. reuteri (CRL1098) – X
Lb. rhamnosus (GG; GR-1) X –
Lb. salivarius (LS01) X –
Antimutagenic and B. animalis (DN-173010) – X Di Cerbo et al. (2016), O’Callaghan and van Sinderen (2016), and Shah (2007)
anticarcigenic B. lactis (Bb12; LAFTI-B94) X X
properties B. infantis (ATCC15697) – X
B. longum (25; 913; BB536) – X
E. faecalis X –
Lb. acidophilus (145; LAFTI- X X
L10; NCFM)
Lb. brevis (CD2) X –
Lb. bulgaricus (2 9 1) – X
Lb. casei (CRL431) – X
Lb. rhamnosus (GG; LC705) X X
P. freundenreichii subsp. X –
shermanii
S. thermophilus (DN-001158; – X
F4; V3)
Antioxidant activities B. bifidum (ATCC29521) – X Bouhafs, Moudilou, Exbrayat, Lahouel, and Idoui (2015), Di Cerbo et al. (2016), Ito
B. lactis (DSMZ23032) – X et al. (2015), Ito et al. (2008), Ito et al. (2003), Terahara et al. (2001), Tian et al.
B. longum (51 A) – X (2015), Vieira et al. (2015), and Wang, Xu, Xu, Zeng, and Wei (2016)
Lb. acidophilus (DSMZ23033) – X
Lb. brevis (DSMZ23034) – X
Lb. bulgaricus (2038) – X
Lb. plantarum (BJ0021) – X
Lb. rhamnosus (CCFM1107) – X
S. thermophilus (YIT2001) – X
Modulation of the B. breve (YIT4064) – X Ogita et al. (2015), Palma et al. (2015), and Shah (2007)
immune system Lb. casei (Shirota) – X
Lb. rhamnosus (OLL2838) – X
S. boulardii (LV01) – X
S. cerevisiae (CNCMI-3856; – X
LV02; UFMG905)
Hypocholesterolemic B. lactis X – Di Cerbo et al. (2016)
effect Lb. acidophilus (L1) X –
Lb. plantarum (CECT7527; X –
CECT7528; CECT7529)
Lb. reuteri (NCIMB 30242) X –

It is widely admitted that probiotics must survive through the
human gastrointestinal tract (GI) to exert their beneficial health
effects. Therefore, they have to resist to GI stresses, such as low
pH, bile salts and pancreatic secretions. Besides, the dose required
for a probiotic effect is still debated, due to fluctuations depending
on both the strain and target. Nevertheless, the minimal concentra-
tion of cells needed to obtain a clinical effect was quoted to be
106 CFU/mL in the small bowel and 108 CFU/mL in the colon
(Minelli & Benini, 2008). Probiotics can be commercialized as
freeze dried or encapsulated microorganisms in form of tablet, cap-
sule or powder or they can be integrated into food products
(Foligné, Daniel, & Pot, 2013). Hitherto, fermented food and espe-
cially dairy products have been the main vectors of probiotic
administration to humans (Nagpal et al., 2012). The mode of probi-
otic administration must be carefully considered as it can highly
affect the persistence of the probiotic in the human digestive tract
(Blanquet-Diot et al., 2012; Pitino et al., 2012; Possemiers,
Marzorati, Verstraete, & Van de Wiele, 2010).
Many of probiotics currently used come from the human intes-
tine. Among them, are lactic acid bacteria (LAB) such as Lactobacil-
lus (e.g., Lactobacillus (Lb.) acidophilus, Lb. rhamnosus and Lb. casei),
Bifidobacterium (e.g., Bifidobacterium (B.) lactis, B. bifidum and B.
breve) or Enterococci (e.g., Enterococcus (E.) faecalis) and some spe-
cies of fungi (e.g., Saccharomyces (S.) boulardii and S. cerevisiae).
Among LAB, Streptococcus (S.) thermophilus or Lb. delbrueckii subsp.
bulgaricus, which are traditionally used in yogurt production, have
not been considered as probiotics during a long time by most sci-
entists as they were not found to survive in the GI tract (Senok
et al., 2005). However, in 2010, yogurt which is the product of milk
fermentation by these two bacteria has obtained the European
Food Safety Agency (EFSA) scientific substantiation of health claim
for lactose digestion improvement. The target population is indi-
viduals with lactose maldigestion and the yogurt should contain
at least 108 CFU live starter microorganisms per gram of fermented
product (EFSA, 2010). Even if yogurt properties are recognized by
EFSA, the probiotic status of S. thermophilus itself is still
questioned.
In this context, the aim of the present review is to give an
update on the probiotic status of S. thermophilus by summarizing
the current published information related to its ability to survive
in the digestive environment and its beneficial effects on host
health.
78 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
2. S. thermophilus: a key LAB in dairy production
S. thermophilus is a Gram-positive bacterium showing ovoid
cells occurring in pairs or in short chains. It is a thermophilic bac-
terium with an optimal growth temperature of 42 °C and an aero-
tolerant anaerobe organism. S. thermophilus belongs to the salivar-
ius group which also includes S. salivarius and S. vestibularis
(Facklam, 2002; Gao, Zhi, Li, Klenk, & Li, 2014). The genome of S.
thermophilus is 1.8 Mb (Bai et al., 2016; Bolotin et al., 2004;
Makarova et al., 2006; Sun et al., 2011), making it among the small-
est genomes by comparison to other LAB and other Streptococcus
strains. Genetic studies indicate that S. thermophilus individualized
from other pathogenic Streptococcus species about 7000 years ago
(Delorme, Bartholini, Bolotine, Ehrlich, & Renault, 2010;
Rasmussen et al., 2008). Since the S. thermophilus species diverged
from their pathogenic relatives, it has lost most of the genes
responsible for virulence and have acquired several genes useful
for living in milk (Hols et al., 2005). Analysis of different S. ther-
mophilus genomes revealed genes acquired through horizontal
transfer which encode various functions, such as bacteriocin
biosynthesis, efflux/uptake pumps, cell-envelope protease and pro-
teins involved in peptide uptake and exopolysaccharide biosynthe-
sis (Bolotin et al., 2004; Delorme et al., 2010; Jameh et al., 2016;
Liu, Siezen, & Nauta, 2009; Rasmussen et al., 2008).
S. thermophilus is the only Streptococcus species used in food
industry. Because it has been consumed by humans for centuries
without giving any disease, it is also the only Streptococcus species
to be recognized as a Generally Recognized As Safe bacterium by
the Food and Drug Administration (FDA). S. thermophilus is one of
the basic starter bacteria of yogurt and is the second most impor-
tant species of industrial LAB after Lactococcus lactis. Besides the
traditional use of S. thermophilus in preparation of yogurt, it is used
in production of several cheese varieties such as Emmental,
Camembert, Brie, Mozzarella and Parmesan (Fox, McSweeney,
Cogan, & Guinee, 2004; Hols et al., 2005). In yogurt production,
the main role of S. thermophilus is a rapid acidification related to
lactic acid production, but also the production of secondary fer-
mentation products such as formate (Perez, de Antoni, & Añon,
1991), acetaldehyde or diacetyle which contribute to the aromatic
and textural properties of the fermented products. In yogurt starter
cultures, interactions between S. thermophilus and Lb. bulgaricus
are described as proto-cooperation (Hols et al., 2005), which is a
symbiotic relationship between the two species. S. thermophilus
produces CO2 and formic acid which stimulate the growth of Lb.
bulgaricus while Lb. bulgaricus hydrolyses milk proteins releasing
peptides and amino acids that improve S. thermophilus growth
(Sieuwerts, de Bok, Hugenholtz, & van Hylckama Vlieg, 2008). In
cheese industry, S. thermophilus is mainly used in the refining of
hard cheeses through the production of aromatic compounds from
amino acids due to its glutamate dehydrogenase activity (Helinck,
Le Bars, Moreau, & Yvon, 2004).
3. Survival of S. thermophilus in the digestive environment
For a probiotic strain, survival in the human GI tract is often
considered as a key factor to ensure the assigned health effect.
Studies on the survival of S. thermophilus in the digestive environ-
ment were performed either in humans, in animals or in in vitro
models (Table 3).
3.1. Human trials
To investigate the survival of probiotics in human digestive
environment, clinical trials are obviously the golden standard.
However, these studies remain costly and heavy to implement
since they must meet very strict criteria. The survival of S. ther-
mophilus during transit through the human digestive environment
remained controversial for a long period. Several studies suggested
that S. thermophilus did not survive the passage of the human GI
tract (Ballesta, Velasco, Borobio, Argüelles, & Perea, 2008; del
Campo et al., 2005; Pedrosa et al., 1995) while other ones showed
the opposite (Elli et al., 2006; García-Hernández, Moreno, Chuan, &
Hernández, 2012; Mater et al., 2005; Pochart, Dewit, Desjeux, &
Bourlioux, 1989; Venturi et al., 1999). In the studies from
Pedrosa et al. (1995), del Campo et al. (2005) and Ballesta et al.
(2008), fecal samples were collected from volunteers after con-
sumption of yogurt. Detection of S. thermophilus was done by agar
plating or by specific polymerase chain reaction (PCR), but no cell
could be detected in the feces of volunteers. On the contrary,
Pochart et al. (1989) established that S. thermophilus S85 had the
capacity to survive the passage through the upper GI tract, with
at least 109 of the total 1011 ingested cells that survived in the
stomach and reach the small intestine. Other studies detected
viable S. thermophilus in the feces of volunteers at concentrations
ranging between 3.5 and 5.6 log10 CFU/g of feces after ingestion
of 10–11 log10 CFU (Elli et al., 2006; García-Hernández et al.,
2012; Mater et al., 2005; Venturi et al., 1999). During consumption,
the concentration of viable S. thermophilus in the feces rapidly
increased to reach a plateau. Yet, one or two weeks after suspen-
sion of yogurt consumption, S. thermophilus counts dropped below
the detection limit (García-Hernández et al., 2012; Venturi et al.,
1999). Similar results were obtained using a PCR-detection
method, with S. thermophilus disappearing completely from feces
3–9 days after stopping consumption (Brigidi, Swennen, Vitali,
Rossi, & Matteuzzi, 2003). At least two different elements may
explain the contradictory results between the detection and the
non-detection of viable S. thermophilus in feces presented above:
the type of agar medium used to detect S. thermophilus living cells
from feces, and the strains used in these experiments. Indeed, Elli
et al. (2006) have shown that the detection of S. thermophilus in
feces was strongly dependent on the medium used, and it was
observed in vitro (see below) that the survival of S. thermophilus
in the digestive tract strongly varied from one strain to another
(Junjua et al., 2016; Uriot et al., 2016).
Even if these studies showed that S. thermophilus can survive
the passage through the human GI tract and be found alive in
the feces of people after consumption, it quickly disappears after
cessation of ingestion, in comparison with other LAB that can be
found longer in the feces (Venturi et al., 1999). In addition, as most
of studies in humans were performed from fecal samples, very few
data are available on the survival of S. thermophilus throughout the
different compartments of the human digestive tract. Besides, none
of these studies has investigated the survival of the bacterium
when ingested alone (only within a yogurt or a mix of probiotic
bacteria) and it is most of time impossible to calculate a specific
survival rate for S. thermophilus based on published data in
humans.
3.2. In vivo studies in animal models
Animal experimentation provides a good alternative to human
clinical studies and can be used to predict what would happen in
human digestive environment and apprehend what mechanisms
are involved. However, animal digestive physiology remains differ-
ent from that of human and the results obtained in animals cannot
be directly transposed to humans. To determine the capacity of S.
thermophilus to survive under digestive conditions, different ani-
mal models were used: minipigs (Lick, Drescher, & Heller, 2001),
rabbits (Dilmi-Bouras & Sadoun, 2002), mice (Drouault, Anba, &
Corthier, 2002; Iyer, Tomar, Kapila, Mani, & Singh, 2010; Mater
et al., 2006) and rats (Ben-Yahia, Mayeur, Rul, & Thomas, 2012;
Table 3
Overview of S. thermophilus survival studies in the digestive environment: human trials, in vivo assays in animal models and in vitro experiments.

Studies Materiels and methods Results

Human Subjects Feeding strategies Evaluation of survival Key results
Pochart et al. (1989) 10 healthy adults Single intake of 430 g of Viable count by plating from 1.6  103 bacteria/g detected at 90 min in all the volunteers. 109 cells of the total 1011
yogurt (strain S85) duodenal samples ingested cells survived the stomach and reached the small intestine
Pedrosa et al. (1995) 33 elderly peoples 240 g of yogurt twice a day, Viable count by plating from No viable S. thermophilus detected in the gastric, duodenal and fecal samples
during 12 days gastric, duodenal and fecal
samples
Venturi et al. (1999) 20 UCr patients 3 g of VSL-3 twice a day, Viable count by plating from 7.88 log10 CFU/g of feces reached at days 20 and then remaining stable throughout the
during 1 year fecal samples study; disappeared 15 days after treatment suspension
Brigidi et al. (2003) 10 healthy adults 250 g of yogurt/day or 6 g of Direct quantitative PCR Healthy patients: reached 4  105 cells/g of feces (3 days, yogurt) or 5  106 cells/g of
10 IBD-patients VSL-3/day, during 10 days detection in fecal samples feces (13 days, VSL-3); disappeared 6–9 days after treatment suspension. IBD-patients:
or 2 months reached 107 cells/g of feces after 2 months (VSL-3)
del Campo et al. (2005) 114 healthy adults 375 g/day of pasteurized or PCR detection in fecal samples No S. thermophilus detected in the fecal samples
fresh yogurt during 2 weeks
Mater et al. (2005) 13 healthy adults 125 mL of yogurt twice a Viable count by plating from 6.3  104 CFU/g of feces detected in 82% of samples
day, during 12 days (strain fecal samples
S85)

O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89

Elli et al. (2006) 20 healthy adults 125 g of yogurt twice a day, Viable count by plating, PCR 5.6 log10 CFU/g of feces detected on day 7 in only one subject
during 1 week detection in fecal samples
Ballesta et al. (2008) Healthy adults Pasteurized or fresh yogurt, Viable count by plating, DNA No viable S. thermophilus detected in the fecal samples
during 75 days detection in fecal samples
García-Hernánez et al. 30 healthy adults 250 g of yogurt/day, during Viable count by DVC-FISH from Between 3.11 and 3.72 log10 CFU/g detected in week 2, between 3.46 and 4.48 log10 CFU/g
(2012) 4 weeks (strain CECT801) fecal samples in week 3 and between 3.76 and 4.66 log10 CFU/g in week 4; disappeared 4 weeks after
treatment suspension
Animal Models Feeding strategies Evaluation of survival Key results
Lick et al. (2001) 6 fistulated Göttingen minipigs Single intake of 600 g Viable count by plating and PCR Between 106 and 107 CFU/g of digesta detected between 3 and 6 h; disappeared rapidly
yogurt (strain 55n) detection from ilea digesta after 8 h
Dilmi-Bouras and 12 male rabbits 10 mL of yogurt twice a day, Viable count by plating from 5.2  108 CFU/mL of gastric samples and 6  106 CFU/mL of duodenal samples reached
Sadoun (2002) during 4 days gastric, duodenal and fecal after 1 h and 2 h, resp., and remaining stable throughout the study; 9.0  107 CFU/mL
samples reached after 72 h in fecal samples; disappeared 96 h after treatment suspension
Drouault et al., 2002 6 GF-mice Single intake of 0.5 mL milk Viable count by plating from Did not multiply and did not settle in GI tract of mice, only transited with the meal
cultures (strain FBI3) fecal samples
Mater et al. (2006) GF- and HMA-mice Single intake of 0.5 mL milk Viable count by plating from 107–108 CFU/g reached after 2.5 h then disappeared after 10 h in the small intestine and
cultures (strain FBI3) small intestine and colon 106–107 CFU/g reached after 2.5 h in the colon of the GF-mice; 107–108 CFU/g reached
samples after 1 h then disappeared after 6 h in the small intestine and reached 107 CFU/g after
2.5 h in the colon of the HMA-mice
Iyer et al. (2010) 32 male albino mice 30 g of fermented milk/day Viable count by plating and PCR No viable cell detected in the small intestine; 5 log10 CFU/g detected in the large intestine
during 20 days (strains detection in small and large and 8 log10 CFU/g in the feces; disappeared gradually after the end of the feeding period
RD102 and RD104) intestine and fecal samples
Thomas et al. (2011) 19 GF-rats Single intake of 1 mL milk Viable count by plating from Colonized the ileum and colon; 109–1010 CFU/g of feces reached in week 1 with lactose
cultures (strains LMD-9 and fecal samples and 108–109 CFU/g of feces in week 3 without lactose
LMG18311)
Ben-Yahia et al. (2012) 23 male GF-rats Single intake of 1 mL of Viable count by plating from Colonized the GI tract without lactose: progressively to 2  108 CFU/g of feces; with
milk cultures (strain LMD- fecal samples lactose: enhancement to 7.1  109 CFU/g of feces
9)
In vitro assays Models Tested strains Evaluation of survival Key results
Marteau et al. (1997) TIM model: dynamic stomach and ST20 Viable count by plating Survival decreased rapidly and dropped below 1% after 70 min in the gastric
small intestinal model; kinetics of compartment; 12% survival at 70 min in the duodenal compartment and <5% survival at
gastric and intestinal pH; 6 h 120 min in the ileal compartment, then the count remained stable
digestion at 37 °C
Vinderola and Simulated gastric juice: pH 2 or 3. 8 strains Viable count by plating Loss of 4–5.3 log10 CFU/mL for 6 strains and >6 log10 CFU/mL for 2 strains at pH 3; loss of
Reinheimer (2003) Bile salts: 0.3, 0.5 or 1%; incubation >6 log10 CFU/mL for the 8 strains at pH 2 (3 h); inhibition of growth at 0.5% and 1% of bile
37 °C for 3 h (pH) or 24 h (bile salts) and growth <10% at 0.3% bile (24 h)

(continued on next page)

79

Table 3 (continued)
Studies Materiels and methods
Mozzi et al. (2009) GS model (mouth and stomach
model); 2.5 h digestion at 37 °C;
kinetics of gastric pH
Boke et al. (2010) pH tolerance 2, 2.5, 3 or 6.2; bile salts
resistance: 0.15 or 0.3%; incubation at
40 °C for 2 h
Iyer et al. (2010) pH 2, 3 or 4; bile salts: 0.5, 1 or 2%. GI
stresses: gastric juice pH 1.5, 2 or 3
with or without pancreatic juice 0.5,
1 or 2% of bile salts; incubation at
37 °C for 2 h (pH); 3 h (bile salts); 3 h
(GI stresses)
Ziarno (2010) Simulated gastric juice: pH 2.4;
simulated duodenal juice: 17 g/L bile;
incubation at 37 °C for 5 h (gastric) or
6 h (duodenum)
García-Hernández et al. Simulated gastric juice: pH 2;
(2012) simulated pancreatic juice: pH 8;
incubation for 3 h or 6 h
Fang et al. (2013) Simulated gastric juice: pH 2, 2.5, 2.8
or 3; bile salts: 2%; incubation at
37 °C for 4 h or 12 h
Ziar et al. (2014) Bile salts: 0, 2, 3, 4 g/L, 6 different
carbohydrates (5 g/L); incubation at
37 °C for 12 h
Junjua et al. (2016) pH 2 and 4; bile salts: 0.5 g/L of
sodium cholate and 0.5 g/L of sodium
deoxycholate; incubation at 37 °C for
1h
Kebouchi et al. (2016) BSM: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and
10 mM; incubation at 37 °C for 2 h
Uriot et al. (2016) TIM model: dynamic stomach and
small intestinal model; kinetics of
gastric and intestinal pH; 5 h
digestion at 37 °C
DVC: direct viable count; BSM: equimolar bile salt mixture containing sodium taurocholate, sodium cholate, and sodium deoxycholate; EPS: exopolysaccharide; FISH: fluorescent in situ hybridization; GF: germ-free; GI: gastro-
intestinal; GS: gastric system; HMA: human microbiota-associated; IBD: inflammatory bowel diseases; PCR; polymerase chain reaction; TIM: TNO gastrointestinal model; UCr: ulcerative colitis in remission; VSL-3: preparation of
probiotics.
CRL1190 and M16
2 high and 2 low EPS-
producing strains
RD102 and RD104
12 strains
CECT801
Cold- or non-shocked BCRC
14085
TA040
30 strains
LMD-9
4 strains; 2 food matrices:
non- and fermented milk
Viable count by plating
Viable count by plating
Viable count by plating
Viable count by plating
Viable count by DVC-FISH
Viable count by plating
Viable count by plating
DO600 nm measure for 20 h
(post-stress)
Viable count by plating
Viable count by plating
80
Results
No significant loss: 8.6 log10 CFU/mL detected at pH 4.4 and 7.4 log10 CFU/mL at pH 3 for
CRL1190, 8.7 log10 CFU/mL at pH 4.4 and 8.0 log10 CFU/mL at pH 3 for M16
No viable cell detected at pH 2–2.5 and <7% survival with 0.15% and 0.3% bile salts for low
EPS-producing strains; 30–45% survival at pH 2 and 71% survival with 0.3% bile salts for
high EPS-producing
Few or no viability loss at different pH (2 h) and different bile concentrations (3 h) for
both strains; few or no viability loss at pH 2 and 3 with or without pancreatic juice for
both strains; complete loss of viability at pH 1.5 with or without the pancreatic juice for
both strains for GI stress conditions
Loss of 1.6–3.8 log10 CFU/mL after 5 h in gastric fluid; loss of 2.6–3.8 log10 CFU/mL after
6 h in duodenal fluid
10.9% survival after 3 h in the simulated gastric juice and decrease of 15% of survival in
O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
the simulated pancreatic juice after 6 h
No viable cell detected at pH 2 after 1 h and at pH 2.5 after 1–2 h for cold- or non-shocked
strains; few or no viability loss at pH 2.8 and 3 and with 2% bile salts
Loss of 0.5–1.5 log10 CFU/mL with 3 or 4 g/L bile; bacterial survival more affected in the
presence of glucose (loss of 2 log10 CFU/mL at 4 g/L bile) than with lactose, raffinose,
lactulose, pectin or lactulose
Comparison between non-stressed and stressed cell revealed great diversity of resistance
to the GI tract stresses between strains
Significant loss of 5 log10 CFU/mL observed at 3 mM and no viable cell detected for
concentration higher than 3 mM
Loss of viability when gastric pH reached 2.5 at 45 min and global loss of 2–4 log10 CFU
for 3 tolerant strains; at the end of digestion, counts below 1 log10 CFU for the CNRZ21
sensitive strain in all the digestive compartments; 6.1 and 8.5 log10 units for the sensitive
and the 3 tolerant strains, resp., in the cumulative ileal effluents; higher survival in
fermented milk (1.6%) vs non-fermented milk (0.4%) for LMD-9
 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
Thomas et al., 2011). The results obtained in minipigs, rabbits and
mice matched those found in humans: S. thermophilus survived
through the GI tract and quickly disappeared from feces samples
after cessation of consumption. The results obtained by Mater
et al. (2006) suggested that the disappearance of S. thermophilus
from the digestive tract may be due to competition with intestinal
microbiota. In their study, the survival of S. thermophilus FBI3 was
evaluated in germ-free (GF) and human-microbiota associated
(HMA) mice. When S. thermophilus was no longer administered,
it disappeared faster from the small intestine of HMA-mice (6 h)
than from that of GF-mice (10 h). Other studies in germ-free ani-
mals have shown contradictory results. Drouault et al. (2002) con-
cluded that S. thermophilus FBI3 was not able to settle in GF-mice
while S. thermophilus LMD-9 and LMG18311 could colonized the
ileum and colon of GF-rats (Ben-Yahia et al., 2012; Thomas et al.,
2011). In these latter studies, the colonization was improved by
lactose ingestion and the authors underlined the importance of
glycolytic enzymes and lactose transporters in the ability of S. ther-
mophilus to adapt to the digestive environment and colonize the
digestive tract of rats.
Taken together, these data show that in vivo studies in animals
with defined microbiota provide helpful information, such as fac-
tors required to improve S. thermophilus survival or metabolic
state. Nevertheless, the results obtained seem to vary depending
on the animal models and therefore should be confirmed before
extrapolation to the human situation.
3.3. In vitro experiments
For ethical, regulatory, technical and cost reasons, in vitro assays
are advantageously used as an alternative to in vivo experiments. In
vitro assays provide conditions for a better adjustment of selective
parameters of digestion, such as pH and bile salts concentrations,
as well as a better understanding of their influence on bacterial
survival and physiology.
A large disparity of survival rates was observed when S. ther-
mophilus strains were subjected to pH conditions varying from
1.5 to 4 (Boke, Aslim, & Alp, 2010; Fang, Lai, & Chou, 2013;
García-Hernández et al., 2012; Iyer et al., 2010; Junjua et al.,
2016; Mozzi, Gerbino, Font de Valdez, & Torino, 2009; Vinderola
& Reinheimer, 2003; Ziarno, 2010). However, most of strains were
sensitive to pH values equal or lower than 3. Similarly, the resis-
tance of S. thermophilus to bile salts (bovine or porcine bile salts)
was shown to be widely strain-dependant (Boke et al., 2010;
Fang et al., 2013; García-Hernández et al., 2012; Iyer et al., 2010;
Junjua et al., 2016; Vinderola & Reinheimer, 2003) even if most
of strains were sensitive to bile salts concentrations higher than
0.5% w/v. Kebouchi et al. (2016) have further investigated the
effect of different concentrations of bile salts (0, 0.25, 0.5, 1, 1.5,
2, 3, 4, 5 and 10 mM) including taurine-conjugated bile salts (tau-
rocholate) and unconjugated bile salts (cholate and deoxycholate)
on S. thermophilus LMD-9 and showed that the strain was resistant
to bile salts up to 3 mM (eq 1.5%). In addition, Ziar, Gérard, and
Riazi (2014) and Boke et al. (2010) have shown that carbon sources
and some bacterial factors may influence the ability of S. ther-
mophilus to survive to pH and bile stresses. Bacterial survival was
more affected by bile salts in the presence of glucose than with lac-
tose, mannitol, raffinose, pectin or lactulose. In particular, they
showed that S. thermophilus TA040 displayed the same population
level with 4 g/L bile or without bile when lactose was added to the
incubation medium (Ziar et al., 2014). Boke et al. (2010) also
showed that two high exopolysaccharide (EPS)-producing S. ther-
mophilus strains had a better resistance to acid pH and bile salts
than the two low EPS-producing strains.
Interestingly, Junjua et al. (2016) have classified into six cate-
gories thirty strains of S. thermophilus according to their tolerance
81
to acidic pH (pH 2 and 4), bile salts (0.5 g/L sodium cholate and
0.5 g/L sodium deoxycholate) and 10 mM H2O2 as well as their
adhesion capacity to HT29-MTX intestinal epithelial cells. Adhe-
sion capacity is an important criterion for probiotic strains as it
may increase their ability to colonize the digestive tract. According
to Junjua et al. (2016), class 1 (8 strains) and 2 (5 strains) possess
low adhesion capacity and low resistance to bile salts and H2O2.
Members of class 3 (4 strains) and 4 (8 strains) resisted well to bile
salts and H2O2 but had a low capacity of adhesion. The two strains
of class 5 resisted well to acid stress and displayed the higher
adhesion capacities. The three strains that were able to resist to
pH 2 constituted the class 6.
Even if in vitro experiments in simple static systems bring valu-
able information about S. thermophilus sensitivity to specific
parameters of digestion, they remain far from the complexity of
human digestive physiology. Complex dynamic in vitro models
which more closely reproduce the human digestive environment
can be alternatively used. The dynamic multi-compartmental
TNO gastrointestinal model (TIM) is currently one of the most
complete simulator of the human stomach and small intestine
(Blanquet-Diot et al., 2012; Minekus, Marteau, Havenaar, & Huis
in’t Veld, 1995). This model integrates the main parameters of
human digestion such as pH, body temperature, gastric and ileal
deliveries, peristaltic mixing and transit, gastric, biliary and pan-
creatic secretions, passive absorption of water and digestion prod-
ucts (Blanquet-Diot et al., 2012). Using this model, Marteau,
Minekus, Havenaar, and Huis in’t Veld (1997) showed that 12%
of ingested S. thermophilus ST20 were able to reach the duodenum,
while less than 5% were recovered in the ileal effluents. Among the
four LAB strains tested in that study (S. thermophilus, B. bifidum, Lb.
acidophilus and Lb. bulgaricus), S. thermophilus was found to be the
more sensitive to GI passage (Marteau et al., 1997). In another
recent study using the same in vitro model, Uriot et al. (2016) con-
firmed the low survival rate of S. thermophilus strains, especially in
the small intestine, with recovery percentages in the ileal effluents
less than 1%. Nevertheless, it is important to mention that bacte-
rial amounts in the ileal effluents of the TIM ranged from 6 to
8.5 CFU log10, which is supposed to be high enough to exert a pro-
biotic activity (Minelli & Benini, 2008). These experiments in the
TIM system also confirmed that the survival rates of S. ther-
mophilus is highly strain-dependent: three of the tested strains
LMD-9, PB18O and EBLST20 showed significantly higher survival
capacities to GI conditions than the fourth one CNRZ21 (Uriot
et al., 2016). Analysis of multiple protein functions indicated that
GI low survival capacity could be attributed to the lack of heat
shock protein and urease functions in CNRZ21. This study also
showed that the way how bacteria are administered has an impor-
tant impact on their survival in the digestive tract. Indeed, S. ther-
mophilus LMD-9 survived better in gastric and small intestinal
conditions when cells were administered as fermented milk
(1.6%) rather than delivered as non-fermented milk (0.4%). Fer-
mented milk seems therefore to be a good vehicle for S. ther-
mophilus strains.
Even if, like for animal models, results obtained using in vitro
models cannot be directly extrapolated to humans, these studies
allow a better understanding of the impact of GI parameters, nutri-
tional sources and mode of administration on the survival of S.
thermophilus. In particular, dynamic multi-compartmental in vitro
digestion models, such as the TIM or the Simulator of the Human
Intestinal Microbial Ecosystem (SHIME) (Marzorati et al., 2014;
Molly, Vande Woestyne, & Verstraete, 1993) are useful to decipher
the behavior of probiotics in the successive environments of the
human GI tract and learn how they respond to the main physico-
chemical digestive parameters (such as acid stress or bile but also
oxygen level or fluid shear) in a physiological temporal-spatial
fashion.
82 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
4. Acid and bile resistance mechanisms in S. thermophilus
Variability in GI survival capacity between S. thermophilus sug-
gests than some strains have developed specific resistance mecha-
nisms to the main stresses encountered in the digestive
environment, such as acid pH and bile.
Responses of Gram positive bacteria to acidic stress are less doc-
umented that those of Gram negative bacteria. Cotter and Hill
(2003) describe the acidity resistance of Gram positive bacteria as
‘‘a combination of constitutive and inducible strategies which result
in the removal of protons (H+), alkalization of the external environment,
changes in the composition of the cell envelope, production of general
shock proteins and chaperones, expression of transcriptional regulators,
and responses to changes in cell density”. Few data are available on the
mechanisms of acid resistance for S. thermophilus. Arena et al.
(2006) suggested that the response to acidic stress of S. thermophilus
combines pH homeostasis through over-expression of H+-ATPase,
reduction of intracellular lactic acid by the up-regulation of lactate
dehydrogenase and increase in ammonium concentration by the
up-regulation of urease. In accordance with these data, Uriot et al.
(2016) found that S. thermophilus CNRZ21 which is devoid of the
urease activity had a much lower survival capacity in the TIM sys-
tem than the three other strains which express the enzyme. Never-
theless, the role of urease in S. thermophilus acid tolerance remains
controversial. Even if most of the 30 S. thermophilus strains tested in
Junjua’s study possess the urease function, the authors indicates
that urease does not seem to be a significant factor in acidic stress
tolerance. In addition, Zotta, Ricciardi, Ciocia, Rossano, and
Parente (2008) and Arioli et al. (2010) showed that the urease was
not very active at low acidic pH, closed to that found in the human
stomach. They suggested that urease would rather have a metabolic
role by optimizing the activity of S. thermophilus glycolytic enzymes
(Arioli et al., 2010; Zotta, Ricciardi, Rossano, & Parente, 2008).
Other factors have been proposed to be involved in acid resis-
tance, as they were found to be over-expressed under low pH:
the chaperone GroEL and GroES which are involved in protein
repair, acidic shock proteins (Asp or Hsp in the literature), peroxide
resistance protein Dpr, general stress protein 24, translation elon-
gation factor (EF) G, Tu and Ts, phosphoglycerate mutase and cell
division protein DivIVA (Arena et al., 2006; González-Márquez,
Perrin, Bracquart, Guimont, & Linden, 1997; Zotta et al., 2008).
The role of Hsp in acid tolerance is strengthened by the study of
Tian et al. (2012) who showed that under acid condition (pH 3),
the survival of L. lactis ML23 was improved when cells were har-
boring a plasmid carrying the shsp gene of S. thermophilus St-QC.
When combining the data obtained by Uriot et al. (2016) and
Junjua et al. (2016), it can be observed an obvious correlation
between Hsp and acid tolerance: the three S. thermophilus strains
that are able to survive under pH 2 possess Hsp (LMD-9, PB180
and PB302) and 16 out of the 20 most resistant strains to pH 4 also
possess Hsp. Lastly, amino acid decarboxylases (Trip, Mulder, &
Lolkema, 2012) and antioxidant pathways such as manganese-
dependent superoxide dismutase (MnSOD, sodA gene) (Bruno-
Bárcena, Azcárate-Peril, & Hassan, 2010) may also have a role in
the acid resistance of S. thermophilus. Several of these proteins
involved in stress response (such as SodA, GroEL, EF-Tu) were also
found to be overproduced in feces of rats mono-associated with S.
thermophilus LMD-9 compared to milk growth (Rul et al., 2011).
Bile resistance mechanisms of S. thermophilus are poorly stud-
ied. As for acidity, production of Hsp could be used by S. ther-
mophilus to resist to the deleterious effect of bile salts (Tian
et al., 2012). Besides, it has been recently shown that two
sortase-dependant proteins, PrtS and MucBP, found in the bacterial
cell surface allow a better survival in presence of bile salts
(Kebouchi et al., 2016).
As a conclusion, resistance strategies of S. thermophilus to acid
and bile are composed of a large combination of numerous differ-
ent mechanisms. This may explain the wide variability of tolerance
to GI stresses encountered among S. thermophilus strains.
5. Beneficial health effects of S. thermophilus
A number of recent studies performed in humans or in animals
have shown that S. thermophilus may have beneficial effects on
host health, as described below.
5.1. Alleviation of lactose intolerance
Lactose intolerance is the inability of adults and children to
digest the milk sugar lactose. This is due to a deficiency of the
enzyme b-galactosidase in the brush border of the small intestine.
When the b-galactosidase is present, lactose is hydrolyzed into its
constituent monosaccharides, glucose and galactose, which are
transported across the small intestine epithelium. Individuals with
lactose intolerance suffer from excessive flatulence, abdominal
pains and diarrheas. In 2010, EFSA has granted a health claim to
yogurt for improvement of lactose digestion. The claim was formu-
lated as follows: ‘‘Live yogurt cultures in yogurt improve digestion of
lactose in yogurt in individuals with lactose maldigestion” (EFSA,
2010). This claim is based on 14 human intervention studies. These
studies have shown an enhanced digestion of lactose by persons
with lactose intolerance when consuming fresh yogurt compared
to pasteurized yogurt with reduced or no live bacteria. To bear
the claim, yogurt must contain at least 108 CFU live microorgan-
isms of Lb. bulgaricus and S. thermophilus per gram of fermented
product. The claim has been attributed to yogurt containing both
bacteria, but not to S. thermophilus alone. In order to better under-
stand the specific role of S. thermophilus in lactose intolerance, sev-
eral studies have been performed in gnotobiotic animal models. In
GF mice, orally administrated S. thermophilus cells were able to
produce an active b-galactosidase in the GI tract (Drouault et al.,
2002). When these mice received lactose (4.5% wt/vol) as drinking
water, a significant diminution of lactose in feces was observed
compared to control mice without S. thermophilus cells. Studies
using HMA-mice showed that b-galactosidase production by S.
thermophilus occurred in the second half of the small intestine
but not in the colon (Mater et al., 2006).
Then, even if the beneficial effect of yogurt on alleviation of lac-
tose intolerance is well established by clinical studies, there are
strong proofs in animals but yet no solid evidence in humans that
this effect can be specifically attributed to S. thermophilus.
5.2. Prevention of chronic gastritis
Studies on animal models have shown that S. thermophilus
could prevent the development of gastritis, an inflammatory dis-
ease of the stomach that can be caused by the intensive use of
acetylsalicylic acid (ASA). In the study by Rodríguez, Medici,
Rodríguez, Mozzi, and Font de Valdez (2009), administration of a
daily dose of milk fermented by S. thermophilus CRL1190 (108 -
CFU/day) given for seven days was found to protect mice against
gastritis induced by the administration of ASA. The gastro-
protective effect was clearly attributed to the EPS produced by
the S. thermophilus strain. EPS could stimulate the immune system
and exert an inhibitory effect on ulcer in the host (Rodríguez et al.,
2009). Further studies conducted by the same authors (Rodríguez,
Medici, Mozzi, & Font de Valdez, 2010) indicated that the EPS pro-
duced by S. thermophilus CRL1190 had the same effect than the
Omeprazole drug used for the treatment of gastritis.
 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
As animal studies showed very promising results regarding the
use of a specific S. thermophilus strain in the prevention of chronic
gastritis, it would be interesting to investigate such beneficial
effects in humans. A natural therapy using purified EPS or milk fer-
mented by S. thermophilus CRL1190 would be a relevant alternative
to proton-pump inhibitors, such as Omeprazole, whose use is
restricted by undesirable side effects and drug interactions.
5.3. Prevention of diarrhea
Acute diarrhea is a serious cause of infant mortality that can
result from viral (rotavirus) or bacterial infections in the gut.
Saavedra, Bauman, Oung, Perman, and Yolken (1994) showed that
formula combining B. bifidum and S. thermophilus reduced the inci-
dence of rotavirus-associated diarrhea in infant aged 5–24 months
from 31% (control, n = 26) to 7% (treated group, n = 29). In another
study from the same group (Saavedra, Abi-Hanna, Moore, & Yolken,
2004), healthy infant aged 3–24 months supplemented with live B.
lactis and S. thermophilus were less susceptible to develop colitis,
which consequently reduced the use of antibiotics. In a large study
involving 571 children aged 3–36 months and consulting for acute
diarrhea, administration of five different probiotic preparations
were tested in their effectiveness in reducing diarrhea duration.
The probiotic bacterial mixture including S. thermophilus gave sig-
nificantly shorter diarrhea (70 h) than oral rehydration solution
alone (115 h) (Canani et al., 2007).
Antibiotic-associated diarrhea (AAD) is a common adverse
effect of antibiotic therapy. Scarce studies have investigated the
effectiveness of yogurt consumption in the prevention of AAD. In
the randomized study of Beniwal et al. (2003), adult patients
receiving 227 g of yogurt per day for 8 days developed less diar-
rhea (12.4%, n = 105) than control (23.7%, n = 97). On the opposite,
another randomized study on 369 patients failed to demonstrate
that yogurt had a positive effect on AAD both in children and in
adults (Conway, Hart, Clark, & Harvey, 2007). These contradictory
results may be mostly due to patient complexity but also to the
type of yogurt and ingested dose. In a recent meta-analysis by
Patro-Golab, Shamir, and Szajewska (2015), the authors concluded
that there is insufficient evidence to support or refute the use of
yogurt in preventing AAD, given the small number of trials and
participants as well as the methodological limitations of the
included trials (Patro-Golab et al., 2015).
To conclude, up to date, there are some evidences that yogurt
consumption can reduce the incidence of infectious diarrhea,
which is not clearly demonstrated in AAD. In any case, the benefi-
cial role of S. thermophilus in preventing diarrhea is not yet fully
established and should be further analyzed.
6. Possible mechanisms of action of S. thermophilus on the host
health
6.1. Antimicrobial activity
S. thermophilus is able to synthesize thermophilins which are
bacteriocins, small peptides able to inhibit the growth or kill clo-
sely related bacteria (Dortu & Thonart, 2009). Hitherto, ten ther-
mophilins have been identified from ten different strains of S.
thermophilus (Table 4). Thermophilins have been shown to have
in vitro inhibitory activities against LAB but also against Gram pos-
itive pathogenic strains such as E. faecalis, Clostridium (C.) botuli-
num, Staphylococcus aureus and Listeria monocytogenes (Fontaine
& Hols, 2008; Rossi, Marzotto, Cremonese, Rizzotti, & Torriani,
2013). For example, thermophilin 1277, which is produced by S.
thermophilus SBT1277, shows an antimicrobial activity against sev-
eral LAB and food spoilage bacteria including C. butyricum, C. sporo-
83
genes and Bacillus cereus. Production of thermophilins represents a
significant interest for conservation in food industry because it
may limit the proliferation of pathogenic bacteria in dairy products
fermented by S. thermophilus (Rossi et al., 2013).
In the context of infection with C. difficile, mice treated with
viable S. thermophilus exhibited 46% less weight loss compared
with untreated controls (Kolling et al., 2012). The treatment also
led to lower diarrheal severity, lower pathology scores and
decrease in toxin production. An inverse correlation between the
levels of luminal lactic acid and abundance of C. difficile was also
observed, suggesting that lactic acid produced by S. thermophilus
may impact pathogen growth in the murine system.
Antimicrobial activity is a main trait of probiotic properties. S.
thermophilus is able to produce thermophilins, but as a part of pro-
biotic criteria, it is necessary to test whether these bacteriocins are
produced in the GI tract and are effective against pathogenic bac-
teria in such environment. S. thermophilus also produces lactic acid,
another antimicrobial compound, but this trait, shared by all LAB,
is not specific to this bacterium. Again, it would be interesting to
evaluate the impact of lactic acid production by S. thermophilus
on its capacity to colonize the GI tract and compete against food-
borne pathogens.
6.2. Antioxidant activity
Some promising antioxidant activities of S. thermophilus have
been observed in both in vitro and in vivo models. Among 49 strains
of LAB, S. thermophilus YIT2001 showed the highest inhibitory
activity against lipid peroxidation in liposomes treated by ferrous
iron (Ito, Ohishi, Yoshida, Yokoi, & Sawada, 2003). Feeding iron-
overloaded mice for 2 weeks with S. thermophilus YIT2001 caused
a decrease in lipid peroxide in the colonic mucosa of the animals.
The authors suggested that S. thermophilus YIT2001 may act as a
scavenger of reactive oxygen species or free radicals or may
increase antioxidant capacities of intestinal content, but seemed
not to work through removal of iron (Ito et al., 2003). This strain
was also able to prevent oxidative injuries to the colonic mucosa
and improve the disease activity index in dextran sulfate sodium
(DSS) induced colitis mice, as well as reduce associated anemia
(Ito et al., 2008). In a last study by the same authors (Ito et al.,
2015), S. thermophilus YIT2001 showed the ability to inhibit low
density lipoprotein (LDL) oxidation and reduce aortic fatty lesions
in hyperlipidemic hamsters. S. thermophilus 1131 also had an
inhibiting effect on LDL oxidation in blood samples collected from
one human volunteer (Terahara, Kurama, & Takemoto, 2001). The
underlying mechanisms of such antioxidant effects are not yet
known but could be related to the activity of antioxidant enzymes
produced by S. thermophilus, like SOD or glutathione reductase
(Amaretti et al., 2013; Chang & Hassan, 1997). By using menadione
(a superoxide-generating agent)-sensitive mutants, Thibessard
et al. (2004) have characterized also three genes (tgt, ossF and ossG)
in S. thermophilus CNRZ368 whose action might contribute to
oxidative stress defense.
Taken together, these studies indicate that some S. thermophilus
strains may have a beneficial antioxidant effect both in vitro and
in vivo in animals. Nevertheless, it should be underlined that most
of available studies involve a single strain of S. thermophilus
YIT2001. It seems that several antioxidant mechanisms are
involved and knowledge of a more exhaustive panel of the bacte-
rial potential molecules would facilitate the selection of super
anti-oxydant strains. These results open up new opportunities for
the use of S. thermophilus in the prevention of various diseases
where oxidative stress has been shown to play a key role, such
as ulcerative colitis, colon cancer or artherosclerosis.
 84
Table 4
Characterization of some bacteriocins produced by S. thermophilus.

Thermophilins 110 1277 13 347 580 81 9 A ST-1 T

S. thermophilus ST110 SBT1277 SFi13 347 580 81 LMD-9 ST134 ACA-DC0001 ACA-DC 0040
producing strains
References Gilbreth and Kabuki, Uenishi, Marciset, Villani et al. (1995) Mathot, Ivanova et al. Fontaine and Ward and Somkuti Aktypis and Aktypis,
Somkuti (2005) Watanabe, Seto, Jeronimus- Beliard, and (1998) Hols (2008) (1995) Kalantzopoulos Kalantzopoulos,
and Nakajima Stratingh, Mollet, Thuault (2003) Huis in’t Veld, and
(2007) and Poolman (2003) ten Brink (1998)
(1997)

O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89

Classification ND Lantibiotic Class IIa Class IIa ND ND Class IIa Class IIa Class IV Class II
MW (Da) 4000–4500 3700 ND 2500–6200 ND 4500 ND 1700 30000 2500
Enzyme sensitivity Protease Proteinase K ND a-chymotrypsin, Protease and Proteinase K ND Protease sensitive Pronase and Protease and a-
sensitive and trypsin trypsin, protease K a-amylase and pronase E Amyloglucosidase, trypsin amylase sensitive
Inactivated by sensitive sensitive sensitive sensitive lysozyme and b- sensitive Lysozyme and
a-amylase Pepsin resistant Catalase and amylase resistant lipase resistant
lipase
resistant
Heat sensitivity Stable after 1 h Activity ND Stable after 1 h at Not heat- Not heat- ND Stable after 1 h at Not heat- Inactive after
at 100 °C maintained 100 °C. 50% of resistant resistant 100 °C resistant 20 min at 121 °C
after 1 h at activity loss after Inactive after Inactive after Inactive after
130 °C 15 min at 121 °C 1 h at 60 °C 15 min at 10 min at 60 °C
60 °C
pH tolerance ND Active between ND ND ND Active ND Active between Active between Active between
pH3 and pH10 between pH3 pH3 and pH7 pH3 and pH10 pH1 and pH9
and pH10
Antimicrobial activities E. faecalis C. butylicum B. cereus E. faecalis B. cereus B. cereus L. S. thermophilus S. aureus LAB
/ strains L. lactis C. sprogenes C. botulinum L. lactis C. butyricum B. subtilis monocytogenes L. innocua C. sporogenes
Lb. bulgaricus Lb. acidophilus L. monocytogenes L. monocytogenes C. sporogenes E. coli S. thermophilus E. faecalis C. tyrobutyricum
P. acidilactici Lb. helveticus LAB S. thermophilus E. faecalis E. faecalis
S. thermophilus M. lacticum S. thermophilus Lb.
S. thermophilus monocytogenes
S. typhimurium
No antimicrobial S. aureus L. innocua E. coli C. sporogenes E. coli LAB C. sporogenes E. faecalis
activity/strains S. epidermidis L. Pseudomonas E. coli L. lactis P. damnosus C. tyrobutyrium L. innocua
monocytogenes Salmonella Lb. bulgaricus L. S. aureus S. carnosus
Lb. gasseri Lb. helveticus monocytogenes
S. aureus S. aureus Lb. helveticus
S. aureus

HT: heat treatment; LAB: lactic acid bacteria; MW: molecular weight; ND: not determined.
 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
6.3. Immunomodulation
A number of in vitro studies have investigated the ability of S.
thermophilus strains to modulate the immune response of various
human cell lines, such as intestinal HT-29 cells, Peripheral Blood
Mononuclear Cells (PBMCs), monocyte-derived Dendritic Cells
(moDCs) or human primary macrophages. Depending on the study
and strain tested, either pro-inflammatory or anti-inflammatory
responses were obtained. Kekkonen et al. (2008) found that S. ther-
mophilus THS induced Th1 type cytokines Interleukin (IL)-12 and
Interferon-gamma (IFN-c) as well as Tumor Necrosis Factor-
alpha (TNF-a) in PMBCs. These results are in accordance with those
of Latvala et al. (2008) who showed that the same strain induced
the expression of pro-inflammatory (TNF-a, IL-12, IL-6, Chemokine
CC Ligand -CCL- 20) and Th1 type (IL-12 and IFN-c) cytokines in
moDCs. The same authors confirmed in a more recent study
(Latvala, Miettinen, Kekkonen, Korpela, & Julkunen, 2011) that S.
thermophilus THS is a strong inducer of IL-12 in moDCs, PBMCs
and macrophages. On the contrary, Latvala et al. (2011) showed
that S. thermophilus is a potent inducer of the anti-inflammatory
IL-10 in macrophages. Such anti-inflammatory effect was con-
firmed by the study of Junjua et al. (2016). Among 30 S. ther-
mophilus strains of different origins, they found that most strains
reduced the production of pro-inflammatory IL-8 after co-
incubation with HT-29 cells, while they induced the production
of IL-10 in PBMC. The authors calculated the ration of synthesis
IL-10/IL-12 and showed that three strains (CNRZ21, CNRZ160 and
PB5MJ) displayed a strong and promising in vitro anti-
inflammatory potential with a ratio higher than 100. Such a value
is similar or higher than the one reported for Faecalibacterium
prausnitzii, a commensal bacteria displaying one of the best anti-
inflammatory properties (Sokol et al., 2008). Ogita et al. (2011)
suggested that modulation of Th1/Th17 balance would be one of
the mechanisms used by S. thermophilus ST28 to exert an anti-
inflammatory effect. They showed that heat-killed S. thermophilus
ST28 suppressed IL-17 production in murine splenocytes stimu-
lated with Transforming Growth Factor-beta (TGF-b) plus IL-6
(Ogita, Tanii, Morita, Suzuki, & Tanabe, 2011). This in vitro effect
was confirmed in vivo in DSS-treated mice where oral treatment
by the strain decreased the production of IL-17 and the percent-
ages of Th17 cells in lamina propria lymphocytes (Ogita, Naka-
shima, et al., 2011). Lastly, in a study designed to follow a large
number of cytokines (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFN-c,
TGF-b), Donkor et al. (2012) concluded that S. thermophilus
St1275 induced significant secretion of both pro- and anti-
inflammatory cytokines from PBMC. Interestingly, Del Carmen
et al. (2014) have observed that introducing an antioxidant func-
tions (catalase and SOD) enhances the anti-inflammatory activity
of S. thermophilus strains.
Hitherto, there is no consensus in the literature about the
immunomodulatory properties of S. thermophilus that seem to be
widely dependent on both the strain tested and the type of cells
used. If the anti-inflammatory properties of some specific strains
of S. thermophilus are further demonstrated, they could be involved
in the development of novel therapeutic products that prevent
pathologies where inflammation plays a key role, such as inflam-
matory bowel diseases.
6.4. Effect on intestinal barrier function
Hyper-permeability of the intestinal barrier has been associated
with a variety of pathologic states like infection, celiac disease,
Crohn’s disease or type 1 diabete. Use of probiotic bacteria raises
hope in restoring impaired barrier function. Resta-Lenert and
Barrett (2003) showed that exposure of intestinal cell monolayers
(both HT29 and caco-2 cell lines) to live S. thermophilus ATCC19258
85
and Lb. acidophilus ATCC4356 prevents decrease in trans-epithelial
resistance induced by entero-invasive Escherichia coli (EIEC). The
effect of the two bacteria on resistance was found to be accompa-
nied by maintenance (actin, ZO-1) or enhancement (actinin,
occluding) of cytoskeletal and tight junctional protein phosphory-
lation. S. thermophilus and Lb. acidophilus also enhanced the barrier
function of naive epithelial cells not exposed to any pathogen.
Apart from their effect on barrier function, the authors showed that
pretreatment with the two strains limited the number of adhered
and invasive EIEC. The ability of S. thermophilus to improve intesti-
nal barrier function was confirmed by an in vivo study in 35
healthy human subjects (Del Piano et al., 2014). Supplementation
with S. thermophilus ST10 and tara gum was able to significantly
decrease intestinal permeability, both in the small bowel and in
the colon of the volunteers. The authors observed a parallel
increase in EPS concentration in the fecal material. When embed-
ded in tara gum, EPS would act by forming a film over the inner
surface of the bowel, therefore creating a mechanical barrier.
So far, scarce studies have shown the potential of S. ther-
mophilus in improving epithelial barrier function and should be
further deepened to identify underlying mechanisms. If the benefi-
cial properties of S. thermophilus are confirmed by further in vivo
studies in humans, it opens up new prospects for using this bac-
terium in the management of many pathologies.
6.5. Interactions with intestinal microbiota
There is no available study investigating the interactions
between S. thermophilus and the human intestinal microbiota. Nev-
ertheless, García-Albiach et al. (2008) have evaluated the effect of
yogurt on the gut microbiota of 79 healthy young adults. The main
change observed after yogurt consumption was an increase in the
levels of LAB and C. perfringens to the detriment of Bacteroides.
Then, even if it is generally acknowledged that probiotics act
through beneficial modulation of gut microbiota, much remains
to be done in that field.
7. Conclusion
Critical criteria to be recognized as a probiotic strain which can
be used for manufacturing of functional foods are survival in GI
conditions, non-pathogenicity, proved beneficial health effects
and resistance to industrial process (Miquel et al., 2015; Nagpal
et al., 2012; Vasiljevic & Shah, 2008).
Even if most of S. thermophilus strains appeared to be sensitive
to acid pH and bile salts, human studies have established their abil-
ity to survive passage through the GI tract and transiently colonize
while ingested. In addition, some strains of S. thermophilus have the
ability to adhere to intestinal epithelial cells, which is an important
criterion for probiotic strain selection. This biological mechanism
promoting interactions with the host leads to gut protection and
enhances colonization. With regards to safety, S. thermophilus is
already considered as safe by the FDA. A large number of in vivo
studies in human or animal models have also shown beneficial
health effects for S. thermophilus, such as alleviation of lactose
intolerance, prevention of gastritis and prevention of infectious
diarrhea. The mode of action of S. thermophilus has been already
investigated, by using in vitro assays and animal models. The bac-
terium seems to act mainly through the production of antimicro-
bial compounds (such as thermophilins), but also via its
antioxidant and anti-inflammatory properties or its ability to
enhance epithelial barrier function. Nevertheless, the available
data should be interpreted with caution as in a substantial part
of these studies S. thermophilus was administrated with another
LAB strain or within yogurt. In addition, even if some assumptions
86 O. Uriot et al. / Journal of Functional Foods 37 (2017) 74–89
have been made about mechanisms of action of S. thermophilus,
they need to be confirmed in a larger number of in vivo studies,
first in animals then in human trials. In particular, there is almost
no information about interactions of the bacteria with human gut
microbiota, even if microbiota modulation is a generally acknowl-
edged mode of action for probiotic strains. Knowing that both the
survival and beneficial effects of S. thermophilus are widely strain-
dependent, it is expected that only certain strains could obtain the
probiotic status, after clinical studies. Lastly, the resistance of S.
thermophilus to industrial process is already well established,
mainly in dairy products. This represents a strong advantage for
designing new probiotic dairy food, especially fermented milks,
using the appropriate strains. Indeed, fermented milks and yogurts
benefits from favorable public opinion and are highly consumed
(about 2 kg of yogurt per person worldwide), which should facili-
tate the commercialization of new products of this type. In addi-
tion, the number of alive bacterial cells which reach the colon
can be increased by improving bacteria survival in yogurt, as it
was shown after the addition of the glucose oxidase to this food
(Batista et al., 2015).
Then, this review has presented numerous studies which show
the potential of S. thermophilus as a new promising probiotic
candidate.
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