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Anti-inflammatory Probiotics: Immunomodulation in the Gut and Beyond
Home <https://ndnr.com/> / Autoimmune/Allergy Medicine

<https://ndnr.com/category/autoimmuneallergy-medicine/> /
<https://ndnr.com/wp-content/uploads/2016/04/Screen-Shot-2016-04-08-at-12.25.18-
PM.png>Anti-inflammatory
Probiotics: Immunomodulation in the Gut and Beyond
By Editor1 <https://ndnr.com/author/editor1/>
Posted April 8, 2016 <https://ndnr.com/2016/04/> In Autoimmune/Allergy
Medicine <https://ndnr.com/category/autoimmuneallergy-medicine/>,
Gastrointestinal <https://ndnr.com/category/gastrointestinal/>
Anti-inflammatory Probiotics: Immunomodulation in the Gut and
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immunomodulation-in-the-gut-and-beyond/#comments>
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Fiona McCulloch, BSc, RAc ND
The immune system is divided into 2 segments – the innate and the
adaptive immune system. These 2 arms work together synergistically to
protect the host from infectious disease. In mammals, the adaptive
immune system includes both the systemic and local (mucosal) types,
where cells and molecules interact to provide this protection in a
complex and effective manner. Probiotics have long been used to improve
gastrointestinal (GI) function; however, in recent years their
beneficial systemic effects have taken front and center stage. The
mechanisms of probiotic action include stimulating the secretion of
antimicrobial substances, competitive adherence to the GI mucosa,
strengthening of the intestinal epithelial barrier, and modulation of
the immune system.^1 Recent studies show that changes in the bacterial
composition of the gut
<https://ndnr.com/naturopathic-news/mix-of-bacteria-in-gut-may-depend-more-on-diet-
than-genes/>
are linked to various metabolic and inflammatory diseases, including
inflammatory bowel disease,^2 obesity and type 2 diabetes,^3 and
allergies.^4 Although most probiotics are known to affect the immune
system, it’s been found that different strains may have rather discrete
effects on immune function; the information on this topic is vast and
growing at a rapid pace. This article will attempt to clarify some of
the underlying mechanisms involved in the anti-inflammatory effects of
selected probiotic strains.
The mucosal surface of the GI tract is an area where numerous encounters

with antigens or infectious agents occur. The immune properties of the
digestive mucosa are provided by the gut-associated lymphoid tissue
(GALT). The epithelial cells of the intestine represent the primary
physical barrier, now recognized as the main interface with the
microbiome in the gut, where immune responses are initiated.^5 The
intestinal barrier protects the host from the external environment with
a protective mucous layer, secretory IgA, and the tight junctions, which
are sealed barriers between epithelial cells. Bacteria within the
intestinal lumen can interact with intestinal epithelial and dendritic
cells, macrophages, and lymphocytes.^6
One of the most interesting effects of probiotics is their ability to

modulate the immune system through the induction of cytokines. Probiotic
bacteria induce the secretion of cytokines from epithelial cells;
moreover, they do this in a strain-specific manner.^7 This is a complex
process – and, as such, studies have resulted in conflicting
information, based on the state of the immune system at the time of
probiotic administration, concomitant administration of other probiotic
strains, inflammation or infection at time of administration, and a
variety of other factors. Time will elucidate much more information on
the effects of probiotic strains on the immune system in different
situations for the host.
Inhibiting Inflammation at the Root: NF-*ĸ*B

The key inflammatory signaling channel is nuclear factor-kappa B
(NF-ĸB). This factor is present in an inactive form in the cytoplasm,
bound to an inhibitory molecule – IĸB. When inflammatory stimuli trigger
signaling pathways, this inhibitor molecule is broken down and NF-ĸB is
released to activate the inflammatory cascade.^7 Several probiotic
strains can prevent the degradation of this inhibitory molecule,
reducing the expression of proinflammatory cytokines.
For example, /Lactobacillus rhamnosus/ GG has been found to decrease the

degradation of IĸB and thereby minimize the production of the
inflammatory cytokine, IL-8.^8 Another example of this particular effect
is the pretreatment of epithelial cells with /Lactobacillus casei/
DN-114 001, resulting in inhibition of IĸB degradation and reduced NF-ĸB
activation.^9
Other studies have shown that administration of /Lactobacillus casei

/CRL 431 can increase the cytokine IL-6, and increase IgA-secreting
cells in mice, enhancing the production of the intestinal protector,
IgA.^10
Effects of Probiotics on Dendritic Cells
In addition to the above effects, probiotics can also affect the

dendritic cells (DCs) that extend in between the epithelial cells into
the intestinal lumen. DCs directly sample gut luminal contents and
orchestrate T-lymphocyte responses in the systemic circulation. Certain
strains of probiotics have been shown to regulate the maturation of DCs
and polarize T-cell activity towards Th1, Th2, or T-regulatory responses.
/Lactobacillus paracasei/ CNCM I-4034 (and its supernatant) has been

found to dramatically reduce the production of the Th1 cytokines, IL-6,
IL-8, IL-12, and tumor necrosis factor-alpha (TNF-α) in human intestinal
DCs challenged with /Salmonella typhi/.^11
The combination probiotic VSL#3 has been found to induce

anti-inflammatory IL-10 in DC culture supernatants.^12 IL-10 is a Th2
cytokine that has been found to suppress IL-12 and other inflammatory
cytokines, such TNF-α.^13
Dendritic cells cultured with /Lactobacillus/ /casei /have also been

found to shift their cytokine profile in favor of IL-10, and are able to
prevent type 1 diabetes development upon injection into non-obese
diabetic mice – an animal model for type 1 (autoimmune) diabetes.^14
Since a single injection of /L casei/-treated DCs is insufficient to
mediate long-term protection, the mechanism in this case most likely
involves the induction of regulatory cells.
Activation of Toll-like Receptors by Probiotics
Toll-like receptors are part of the innate immune system in the gut that
recognize and respond to pathogens. These receptors are known to
transmit signals in response to bacteria. It is therefore not surprising
that probiotics which come into contact with immune cells in the gut can
also elicit significant systemic immune responses.^15 It is well
established that the cells that interact most extensively with
probiotics are the intestinal epithelial cells; however, probiotics also
come into contact with DCs and other immune cells, as previously
mentioned. Toll-like receptors (TLRs) are trans-membrane proteins that
are expressed on both immune and non-immune cells ranging from
intestinal epithelial cells to dendritic cells.
Activation of TLRs can signal immune responses in the intestinal

epithelial cells, such as the major inflammatory pathway, NF-ĸB. TLR
signaling can also control the maturation of dendritic cells in the gut.
Probiotic organisms in the gut can alter the immune state by affecting
TLR expression on DCs, shifting the differentiation of T-helper cells
into either Th1, Th2 or Th17.^6 In fact, it’s now thought that specific
types of TLRs create differing immune responses to probiotics.
An example of the action of a probiotic on TLRs is that of

/Lactobacillus casei/ Zhang – a probiotic strain found to increase the
expression of TLR2 and TLR9, thereby reducing the production of TNF-α
and IL-β in a rat model of acute hepatic inflammation.^16
Probiotics can also act as negative regulators of TLRs. /Lactobacillus/

/plantarum/ genomic DNA has been found to inhibit NF-ĸB and
TNF-α production.^17 This inhibition was accompanied by the suppression
of TLR2, TLR4, and TLR9, and an increase in IRAK M, a negative regulator
of TLR.
The Effects of Probiotics on Cytokines & T-Cell Differentiation
Cytokines are produced by different types of immune cells, mainly the

T-lymphocyte subsets. Typically, immune responses with cytokines that
are classified as Th1 and Th17 are pro-inflammatory, whereas Th2
cytokines are typically anti-inflammatory, promote humoral immunity
against extracellular pathogens, and are involved in allergic response.
The Th1 cytokines include IFN-γ, IL-12, TNF-α, IL-2, and IL-17. The Th2
cytokines include IL-10, IL-4 and TGF-β.
Cytokines including IL-10 and TGF-β have been implicated in T-regulatory

cell function, playing a role in suppressing and regulating immune
responses. T-regulatory cells (Tregs) are the police of the immune
system, active in suppressing the development of autoimmune disease in
the ever-changing immune environment.
It is thought that the primary influence of probiotics on the immune

system is on the intestinal epithelial cell. Firstly, probiotics can
improve the integrity of epithelial cells, hence improving immune
response through a secondary mechanism. As an example, /Lactobacillus/
GG produces 2 proteins – p40 and p75 – which protect epithelial cells
from apoptosis, thereby increasing the integrity of the gut barrier.^18
Alternately, probiotics can act directly on immune responses by
promoting cytokine release from the intestinal epithelial cells.
Probiotic Strains and Cytokines
Certain probiotic strains appear to promote the production of specific

cytokines, including IFN-γ, IL-12, IL-2, TNF-α, and IL-6 from Th1/Th17
cells, while some of other probiotic strains may promote the production
of regulatory cytokines, including IL-10 and TGF-β from Tregs^7 :
/L rhamnosus /Lc705 has been found to have a strong downregulating
effect on several proinflammatory genes, such as IL-8 and TNF-α, while
upregulating genes that encode anti-inflammatory cytokines, such
as IL-10^19
/L plantarum/ 2142 has been found to significantly decrease IL-8 and

TNF-α mRNA levels, decreasing Th1 inflammatory responses^20
/Bacillus coagulans/ GB-30 has been found to increase the population of

another intestinal bacteria, /F prausnitzii,^21 / possibly due to the
production of lactic acid by /B coagulans.^2 / /F prausnitzii/ has been
shown to potently induce production of anti-inflammatory cytokines,
specifically IL-10.^21
Similarly, a previous study showed that /Bacillus coagulans/ was able to

stimulate the production of major anti-inflammatory cytokines such as
IL-10^22
Administration of the probiotic yeast, /Saccharomyces boulardii/, to a

group of 37 patients was found to reduce systemic and local
proinflammatory cytokines IL-8 and TNF-α, increase anti-inflammatory
IL-10 levels, and increase the tissue IL-10/IL-12 ratio^23
Patients receiving /Lactobacillus casei/ 01 revealed a significant

difference between IL-10, IL-12, and TNF-α changes over the course of
the study, with a shift towards anti-inflammatory Th2 cytokine release^24
/Lactobacillus casei /DN-114001 has been found to increase the number of

CD4 Fox P3 Tregs in the mesenteric lymph nodes, and decrease the
production of the proinflammatory cytokines TNF-α and IFN-γ^25
In terms of combination products, the probiotic strains found in VSL#3

have been shown to be protective in several animal models of colitis,
including IL-10-deficient mouse models of colitis, and were found to
mediate their effect through the induction of Tregs^26
Th17 & Autoimmunity
Th17 cells represent a population of T cells that are not only important
for fighting bacterial infection, but are also involved in the
pathogenesis of a number of inflammatory and autoimmune diseases.
Th17 cell responses appear to be induced by a restricted number of

microbial species, such as the segmented filamentous bacteria (SFB) –
gram-positive bacteria within the /Firmicutes/ phylum.^27 ^ SFB are
thought to play a key role in the maturation of the adaptive mucosal
immune response in the gut. A microbiota favoring SFB could therefore
have an impact on immune response and, consequently, on the development
of Th17-mediated inflammatory/autoimmune diseases in the gut and at
distant sites in predisposed individuals.
/Lactobacillus plantarum/ has been found to decrease the colonization

and survival of SFB in mice, restoring SFB-dominant GI tracts to a
healthy level.^28 As such, it may be inferred that this strain may be
beneficial in reducing some of the stimulus for Th17 and autoimmunity.
In another recent report, colonization of germ-free mice with the human

commensal, /Bacteroides fragilis/, was shown to induce IL-10 production
and Foxp3 expression, decrease Th17 cells, and prevent colitis
development. /B fragilis/ is not yet available as a commercial
probiotic, however.
Finally, oral administration of different probiotic species has been

shown to protect against development of various Th17-mediated autoimmune
diseases, such as type 1 diabetes /(L casei/),^29 experimental
autoimmune encephalomyelitis (/L paracasei /DSM 13434, /L plantarum/ DSM
15312 and DSM 15313),^30 and experimental rheumatoid arthritis (/L
casei/^24,31 ) via induction of IL-10-producing Tregs and attenuation of
Th1 and Th17 cytokines.
Metabolic Inflammation
It’s well known that there is a central inflammatory component to

metabolic disease and that the microbiome is significantly altered in
metabolic disorders
<https://ndnr.com/autoimmuneallergy-medicine/autoimmunity-and-the-gut/>.^32
Treatment of metabolic disorders with drugs such as metformin, or
natural products such as berberine, can shift the microbiome, increasing
the production of anti-inflammatory short-chain fatty acids; this may be
a major mechanism through which these agents improve metabolism.^33
Specific probiotic strains have been found to affect metabolic
inflammation. For example, /Lactobacillus casei/ CRL 431 administration
decreased inflammatory cytokines in a diet-induced obese mouse model,
including TNF-α, IL-6, and IL-17.
/Lactobacillus gasseri/ SBT 2055, /Lactobacillus rhamnosus/ ATCC 53103,

and the combination of /L rhamnosus/ ATCC 53102 and /Bifidobacterium
lactis/ Bb12 may improve short-chain fatty acid production and reduce
the low-grade inflammation that is central in obesity and metabolic
disorders.^34
/Saccharomyces boulardii/ has also been found to attenuate the markers

of metabolic inflammation in mice, reducing body weight, fat mass,
hepatic steatosis, and overall inflammatory tone.^35
Comparing Immune Effects of Lactobacilli & Bifidobacteria
Another interesting study compared the cytokine profiles of different

strains, examining the ratios of key cytokines, IL-10/IL-12, and
TNF-α/IL-10.^36 In this study, distinct patterns emerged for
Lactobacilli and Bifidobacteria strains: Bifidobacteria, in particular,
produced a high ratio of IL-10/IL-12 (Th2 dominance), whereas
/Lactobacillus/ strains tended to produce a high ratio of TNF-α/IL-10
(Th1 dominance).^36 Although this is of interest, there are clearly
Lactobacilli that have potent anti-inflammatory effects, so this should
not be taken as a generalization.
Care should also be taken to not view Th1 patterns as negative when it
comes to inflammation. In fact, the Th1 branch of the immune system is
protective against cancer, allergy, and infection – as such, its
activation is exceptionally beneficial for the appropriate patient
population.
In terms of anti-inflammatory Bifidobacteria species, /Bifidobacterium

breve/ has been found to increase Th2- and Treg-associated cytokines in
the distal colon, leading to increases of Treg and decreases of Th17
cell subsets in Peyer’s patches of mice with intestinal inflammation.^37
/Bifidobacterium infantis/ is a well-researched probiotic that has been

shown to adhere to GI epithelial cell lines without inducing NF-ĸB
activation or the secretion of chemokines.^38 /B infantis/ has been
found to reduce Th1- and Th17-related cytokines and increase
Treg-related molecules in mice with colitis.^39
The effects of /B infantis/ also go beyond the gut mucosa and into the
periphery: /B infantis/ 35624 feeding reduced inflammatory markers in
patients with ulcerative colitis, chronic fatigue syndrome, and
psoriasis when compared with placebo.^40 Interestingly, plasma TNF-α was
reduced in chronic fatigue syndrome (CFS) and psoriasis, while IL-6 was
reduced in ulcerative colitis and CFS.
Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6

secretion by peripheral blood mononuclear cells (PBMCs) was
significantly reduced in /B infantis/ 35624-treated groups compared with
placebo following 8 weeks of treatment.
Th1 Inducers – Benefits for Allergic Inflammation
We have talked about inducing Th2 with probiotics, which would produce
anti-inflammatory effects for both metabolic and autoimmune-mediated
inflammation. However, allergy is another important inflammatory
disease, mediated by high levels of Th2 cytokines. As an example of a
Th1-inducing effect in a probiotic strain, /L acidophilus /(ATCC4356)
has been found to increase the production of IFN-γ and decrease the
production of IL-4 (a Th2 cytokine) in spleen cell culture.^41
/B bifidum/ PRL2010 enhances production of IL-6 and IL-8 cytokines,

presumably through NF-κB activation, resulting in a Th1 response.^42
/L acidophilus/ AD031, /Bifidobacterium lactis/ AD011, and the

combination of /L acidophilus /AD031 and /B lactis/ AD011, have also
been found to induce a Th1 response, thereby reducing mast cells and
eosinophils.^43 These strains are thus likely indicated for those with
allergic conditions that are Th2-dominant; however, more research is
needed to determine if these strains may have unwanted effects in
Th1-dominant immune conditions.
Other Factors & Important Considerations
It’s important to note that other factors may impact the effect of
probiotics on the immune system.
Dosing of probiotics may be impactful; for example, low-dose /L

acidophilus /NCFM has been found to significantly increase IFN-γ (a Th1
cytokine) and downregulate T-regulatory cell responses, when compared
with high doses of the same probiotic and control groups.^44 High doses
of the same strain have also been shown to increase the production of
Tregs. Unfortunately, there is currently little information on the
dose-dependent effects of probiotic strains, but this remains an area of
interest for further research.
As seen above, the combination of different probiotic strains also

impacts the effect of a probiotic, as does the baseline inflammatory
state of the host.
Dietary factors also likely play a profound role

<https://ndnr.com/autoimmuneallergy-medicine/food-sensitivities-and-epigenetics/>
in the immunological effects of probiotics – clearly another area for
further investigation.
Although the effects of probiotics on the immune system are fascinating,

the mechanisms and connections of their actions are still emerging. More
research will help to clarify better probiotic and nutritional treatment
strategies to benefit patients with a variety of immune and inflammatory
conditions.
------------------------------------------------------------------------
McCullochFiona McCulloch, BSc, RAc, ND, graduated from the Canadian

College of Naturopathic Medicine in Toronto, Ontario. Her undergraduate
degree is in biological sciences from the University of Guelph (Guelph,
Ontario). She is the founder of White Lotus Integrative Medicine in
Toronto, and her clinical practice is focused on her passion: women’s
health, endocrinology, autoimmunity, and fertility concerns. She has
published numerous articles on the topics of evidence-based medicine for
infertility and women’s health concerns, and is set to publish her first
book, /PCOS: Fertility Restored./
*References*
1. Collado MC, Gueimonde M, Salminen S. Probiotics in adhesion of

pathogens: mechanisms of action. In: Watson RR, Preedy VR, eds.
/Bioactive Foods in Promoting Health/. Cambridge, MA: Academic
Press, Elsevier; 2010.
2. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii
is an anti-inflammatory commensal bacterium identified by gut
microbiota analysis of Crohn disease patients. /Proc Natl Acad Sci U
S A/. 2008;105(43):16731-16736.
3. Everard A, Belzer C, Geurts L, et al. Cross-talk between Akkermansia
muciniphila and intestinal epithelium controls diet-induced obesity.
/Proc Natl Acad Sci U S A/. 2013;110(22):9066-9071.
4. Berni Canani R, Sangwan N, Stefka AT, et al. Lactobacillus rhamnosus
GG-supplemented formula expands butyrate-producing bacterial strains
in food allergic infants. /ISME J/. 2016;10(3):742-750.
5. Koch S, Nusrat A. The life and death of epithelia during
inflammation: lessons learned from the gut. /Annu Rev Pathol/.
2012;7:35-60.
6. Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, et al. Probiotic
mechanisms of action. /Ann Nutr Metab/. 2012;61(2):160-174.
7. Kemgang TS, Kapila S, Shanmugam VP, Kapila R. Cross-talk between
probiotic lactobacilli and host immune system. /J Appl Microbiol/.
2014;117(2):303-319.
8. Zhang L, Li N, Caicedo R, Neu J. Alive and dead Lactobacillus
rhamnosus GG decrease tumor necrosis factor-alpha-induced
interleukin-8 production in Caco-2 cells. /J Nutr/.
2005;135(7):1752-1756.
9. Tien M-T, Girardin SE, Regnault B, et al. Anti-inflammatory effect
of Lactobacillus casei on Shigella-infected human intestinal
epithelial cells. /J Immunol/. 2006;176(2):1228-1237.
10. Galdeano CM, Perdigon G. The Probiotic Bacterium Lactobacillus casei
Induces Activation of the Gut Mucosal Immune System through Innate
Immunity. /Clin Vaccine Immunol/. 2006;13(2):219-226.
11. Bermudez-Brito M, Muñoz-Quezada S, Gomez-Llorente C, et al. Human
intestinal dendritic cells decrease cytokine release against
Salmonella infection in the presence of Lactobacillus paracasei upon
TLR activation. /PLoS One/. 2012;7(8):e43197.
12. Drakes M, Blanchard T, Czinn S. Bacterial probiotic modulation of
dendritic cells. /Infect Immun/. 2004;72(6):3299-3309.
13. Rossato M, Curtale G, Tamassia N, et al. IL-10-induced microRNA-187
negatively regulates TNF-α, IL-6, and IL-12p40 production in
TLR4-stimulated monocytes. /Proc Natl Acad Sci U S A/.
2012;109(45):E3101-E3110.
14. Manirarora JN, Parnell SA, Hu YH, et al. NOD dendritic cells
stimulated with Lactobacilli preferentially produce IL-10 versus
IL-12 and decrease diabetes incidence. /Clin Dev Immunol/.
2011;2011:630187.
15. Lebeer S, Vanderleyden J, De Keersmaecker SC. Host interactions of
probiotic bacterial surface molecules: comparison with commensals
and pathogens. /Nat Rev Microbiol/. 2010;8(3):171-184.
16. Wang Y, Xie J, Li Y, et al. Probiotic Lactobacillus casei Zhang
reduces pro-inflammatory cytokine production and hepatic
inflammation in a rat model of acute liver failure. /Eur J Nutr/.
2015 Apr 2015. [Epub ahead of print]
17. Kim CH, Kim HG, Kim JY, et al. Probiotic genomic DNA reduces the
production of pro-inflammatory cytokine tumor necrosis factor-alpha.
/FEMS Microbiol Lett/. 2012;328(1):13-19.
18. Yan F, Cao H, Cover TL, et al. Soluble proteins produced by
probiotic bacteria regulate intestinal epithelial cell survival and
growth. /Gastroenterology/. 2007;132(2):562-575.
19. Oksaharju A, Kankainen M, Kekkonen RA, et al. Probiotic
Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in
human mast cells. /World J Gastroenterol/. 2011;17(6):750-759.
20. Paszti-Gere E, Szeker K, Csibrik-Nemeth E, et al. Metabolites of
Lactobacillus plantarum 2142 prevent oxidative stress-induced
overexpression of proinflammatory cytokines in IPEC-J2 cell line.
/Inflammation/. 2012;35(4):1487-1499.
21. Nyangale EP, Farmer S, Cash HA, et al. Bacillus coagulans GBI-30,
6086 Modulates Faecalibacterium prausnitzii in Older Men and Women.
/J Nutr/. 2015;145(7):1446-1452.
22. Jensen GS, Benson KF, Carter SG, Endres JR. GanedenBC30 cell wall
and metabolites: anti-inflammatory and immune modulating effects in
vitro. /BMC Immunol/. 2010;11:15.
23. Abbas Z, Yakoob J, Jafri W, et al. Cytokine and clinical response to
Saccharomyces boulardii therapy in diarrhea-dominant irritable bowel
syndrome: a randomized trial. /Eur J Gastroenterol Hepatol/.
2014;26(6):630-639.
24. Alipour B, Homayouni-Rad A, Vaghef-Mehrabany E, et al. Effects of
Lactobacillus casei supplementation on disease activity and
inflammatory cytokines in rheumatoid arthritis patients: a
randomized double-blind clinical trial. /Int J Rheum Dis/.
2014;17(5):519-527.
25. Zakostelska Z, Kverka M, Klimesova K, et al. Lysate of probiotic
Lactobacillus casei DN-114 001 ameliorates colitis by strengthening
the gut barrier function and changing the gut microenvironment.
/PLoS One/. 2011;6(11):e27961.
26. Di Giacinto C, Marinaro M, Sanchez M, et al. Probiotics ameliorate
recurrent Th1-mediated murine colitis by inducing IL-10 and
IL-10-dependent TGF-beta-bearing regulatory cells. /J Immunol/.
2005;174(6):3237-3246.
27. Snel J, Heinen PP, Blok HJ, et al. Comparison of 16S rRNA sequences
of segmented filamentous bacteria isolated from mice, rats, and
chickens and proposal of “Candidatus Arthromitus”. /Int J Syst
Bacteriol/. 1995;45(4):780-782.
28. Fuentes S, Egert M, Jimenez-Valera M, et al. A strain of
Lactobacillus plantarum affects segmented filamentous bacteria in
the intestine of immunosuppressed mice. /FEMS Microbiol Ecol/.
2008;63(1):65-72.
29. Matsuzaki T, Nagata Y, Kado S, et al. Prevention of onset in an
insulin-dependent diabetes mellitus model, NOD mice, by oral feeding
of Lactobacillus casei. /APMIS/. 1997;105(8):643-649.
30. Lavasani S, Dzhambazov B, Nouri M, et al. A novel probiotic mixture
exerts a therapeutic effect on experimental autoimmune
encephalomyelitis mediated by IL-10 producing regulatory T cells.
/PLoS One/. 2010;5(2):e9009.
31. So JS, Kwon H-K, Lee CG, et al. Lactobacillus casei suppresses
experimental arthritis by down-regulating T helper 1 effector
functions. /Mol Immunol/. 2008;45(9):2690-2699.
32. Devaraj S, Hemarajata P, Versalovic J. The human gut microbiome and
body metabolism: implications for obesity and diabetes. /Clin Chem/.
2013;59(4):617-628.
33. Zhang X, Zhao Y, Xu J, et al. Modulation of gut microbiota by
berberine and metformin during the treatment of high-fat
diet-induced obesity in rats. /Sci Rep/. 2015;5:14405.
34. Mekkes MC, Weenen TC, Brummer RJ, Claassen E. The development of
probiotic treatment in obesity: a review. /Benef Microbes/.
2014;5(1):19-28.
35. Everard A, Matamoros S, Geurts L, et al. Saccharomyces boulardii
administration changes gut microbiota and reduces hepatic steatosis,
low-grade inflammation, and fat mass in obese and type 2 diabetic
db/db mice. /MBio/. 2014;5(3):e01011-e01014.
36. Dong H, Rowland I, Yaqoob P. Comparative effects of six probiotic
strains on immune function in vitro. /Br J Nutr/. 2012;108(3):459-470.
37. Zheng B, van Bergenhenegouwen J, Overbeek S, et al. Bifidobacterium
breve attenuates murine dextran sodium sulfate-induced colitis and
increases regulatory T cell responses. /PLoS One/. 2014;9(5):e95441.
38. O’Hara AM, O’Regan P, Fanning A, et al. Functional modulation of
human intestinal epithelial cell responses by Bifidobacterium
infantis and Lactobacillus salivarius. /Immunology/.
2006;118(2):202-215.
39. Zuo L, Yuan KT, Yu L, et al. Bifidobacterium infantis attenuates
colitis by regulating T cell subset responses. /World J
Gastroenterol/. 2014;20(48):18316-18329.
40. Groeger D, O’Mahony L, Murphy EF, et al. Bifidobacterium infantis
35624 modulates host inflammatory processes beyond the gut. /Gut
Microbes/. 2013;4(4):325-339.
41. Imani Fooladi AA, Yazdi MH, Pourmand MR, et al. Th1 Cytokine
Production Induced by Lactobacillus acidophilus in BALB/c Mice
Bearing Transplanted Breast Tumor. /Jundishapur J Microbiol/.
2015;8(4):e17354.
42. Turroni F, Taverniti V, Ruas-Madiedo P, et al. Bifidobacterium
bifidum PRL2010 modulates the host innate immune response. /Appl
Environ Microbiol/. 2014;80(2):730-740.
43. Kim JY, Choi YO, Ji GE. Effect of oral probiotics (Bifidobacterium
lactis AD011 and Lactobacillus acidophilus AD031) administration on
ovalbumin-induced food allergy mouse model. /J Microbiol
Biotechnol/. 2008;18(8):1393-1400.
44. Wen K, Li G, Bui T, et al. High dose and low dose Lactobacillus
acidophilus exerted exerted differential immune modulating effects
on T cell immune responses induced by an oral human rotavirus
vaccine in gnotobiotic pigs. /Vaccine/. 2012;30(6):1198-1207.
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Anti-inflammatory Probiotics: Immunomodulation in the Gut and Beyond

Home <https://ndnr.com/> / Autoimmune/Allergy Medicine

Anti-inflammatory Probiotics: Immunomodulation in the Gut and Beyond

Fiona McCulloch, BSc, RAc ND

The mucosal surface of the GI tract is an area where numerous encounters

One of the most interesting effects of probiotics is their ability to

Inhibiting Inflammation at the Root: NF-*ĸ*B

For example, /Lactobacillus rhamnosus/ GG has been found to decrease the

Other studies have shown that administration of /Lactobacillus casei

Effects of Probiotics on Dendritic Cells

In addition to the above effects, probiotics can also affect the

/Lactobacillus paracasei/ CNCM I-4034 (and its supernatant) has been

The combination probiotic VSL#3 has been found to induce

Dendritic cells cultured with /Lactobacillus/ /casei /have also been

Activation of Toll-like Receptors by Probiotics

Activation of TLRs can signal immune responses in the intestinal

An example of the action of a probiotic on TLRs is that of

Probiotics can also act as negative regulators of TLRs. /Lactobacillus/

The Effects of Probiotics on Cytokines & T-Cell Differentiation

Cytokines are produced by different types of immune cells, mainly the

Cytokines including IL-10 and TGF-β have been implicated in T-regulatory

It is thought that the primary influence of probiotics on the immune

Probiotic Strains and Cytokines

Certain probiotic strains appear to promote the production of specific

/L plantarum/ 2142 has been found to significantly decrease IL-8 and

/Bacillus coagulans/ GB-30 has been found to increase the population of

Similarly, a previous study showed that /Bacillus coagulans/ was able to

Administration of the probiotic yeast, /Saccharomyces boulardii/, to a

Patients receiving /Lactobacillus casei/ 01 revealed a significant

/Lactobacillus casei /DN-114001 has been found to increase the number of

In terms of combination products, the probiotic strains found in VSL#3

Th17 & Autoimmunity

Th17 cell responses appear to be induced by a restricted number of

/Lactobacillus plantarum/ has been found to decrease the colonization

In another recent report, colonization of germ-free mice with the human

Finally, oral administration of different probiotic species has been

It’s well known that there is a central inflammatory component to

/Lactobacillus gasseri/ SBT 2055, /Lactobacillus rhamnosus/ ATCC 53103,

/Saccharomyces boulardii/ has also been found to attenuate the markers

Comparing Immune Effects of Lactobacilli & Bifidobacteria

Another interesting study compared the cytokine profiles of different

In terms of anti-inflammatory Bifidobacteria species, /Bifidobacterium

/Bifidobacterium infantis/ is a well-researched probiotic that has been

Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6

Th1 Inducers – Benefits for Allergic Inflammation

/B bifidum/ PRL2010 enhances production of IL-6 and IL-8 cytokines,

/L acidophilus/ AD031, /Bifidobacterium lactis/ AD011, and the

Other Factors & Important Considerations

Dosing of probiotics may be impactful; for example, low-dose /L

As seen above, the combination of different probiotic strains also

Dietary factors also likely play a profound role

Although the effects of probiotics on the immune system are fascinating,

McCullochFiona McCulloch, BSc, RAc, ND, graduated from the Canadian

1. Collado MC, Gueimonde M, Salminen S. Probiotics in adhesion of

Cytokins <https://ndnr.com/tag/cytokins/>, Dendritic Cells

* Small Intestine Bacterial Overgrowth: The Case of the Perpetual

Biofilms: What Have We Learned from the Research?

Neuropathy & Long-term PPI Use: A Case Study

Inhibiting Inflammation at the Root: NF-ĸB