Dr.

Andrei Manu-Marin
Medic primar urolog
Specializare în neuro-urologie
MICROBIOTA
URINARA

ANDREI MANU-MARIN
EVOMED
MICROBIOTA / MICROBIOM

 “microbiota” (the microbes themselves)

 “microbiome” (the genetic material of those microbes)
 MICROBIOM – US-NIH – proiect lansat in 2007
 Gut Microbiota – rol in – afectiuni psihice, cardio-vasculare, metabolismul osos, imunitate/HIV, alergie
 Microbiota–Gut–Brain Axis – Neufeld KM, NeuroGastroenterol Motil 23.255-264 (2011) starea psihica+comportament
 UROBIOM – lansat in 2012
 Urobiota – este diferita la femeile cu incontinenta si la cele cu dureri vezicale cronice.
 MICROBIOTA –
FEMEI

CONTINENTE
(NON-UUI)

VS

INCONTINENTE
Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, (UUI)
Zilliox, MJ, Brincat C, Price TK, et al. Incontinence medication response relates to the
female urinary microbiota. Int Urogynecol J. 2015
 MICROBIOTA SPECII
BACTERIENE

FEMEI INCONTINENTE
FEMALE URINARY MICROBIOTA (FUM)

 Menopausal women not on exogenous hormones had increased microbial diversity and their FUM was less likely
to be predominated by a single microbe.
 A similar relationship was observed between microbial diversity and UUI symptoms.
 These results suggest that predominance (most often by Lactobacillus species) is typical of hormone-positive
women and that loss of that predominance might be associated with UUI symptoms
 Intriguingly, while Lactobacillus crispatus in the FUM was associated with the non-symptomatic controls,
Lactobacillus gasseri in the FUM was associated with UUI.

• Curr Opin Obstet Gynecol. 2016 October ; 28(5): 407–412. doi:10.1097/GCO.0000000000000298. MS1. Linda Brubaker, MD, and Alan Wolfe
• Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, et al. The female
urinary microbiome: a comparison of women with and without urgency urinary incontinence. MBio. 2014; 5:e01283–01214
EXPANDED QUANTITATIVE URINE CULTURE (EQUC)

 Each catheterized urine sample was processed following the standard urine culture procedure by the clinical
microbiology lab and then was processed using the EQUC procedure.
 For EQUC, 0.1 ml of urine was inoculated onto BAP (sheep Blood Agar Plate), chocolate and colistin, and
nalidixic acid (CNA) agars (BD BBL prepared plated media - Becton, Dickinson and Co., Sparks, MD), streaked for
quantitation, and incubated in 5% CO2 at 35°C for 48 h.
 For UTI diagnosis, each uropathogen may have its own unique threshold (e.g., 102 CFU/ml for Aerococcus
urinae, 103 CFU/ml for Streptococcus agalactiae, and 104 CFU/ml for Klebsiella pneumoniae).

Urine Is Not Sterile: Use of Enhanced Urine Culture Techniques To Detect Resident Bacterial Flora in the Adult Female Bladder.
Evann E. Hilt, Kathleen McKinley, Meghan M. Pearce, Amy B. Rosenfeld, Michael J. Zilliox, Elizabeth R. Mueller, Linda Brubaker, Xiaowu Gai, Alan J. Wolfe, Paul
C.Schreckenbergera. March 2014 Volume 52 Number 3 Journal of Clinical Microbiology p. 871–876
 MICROBIOTA IN CISTITA ACUTA

Average CFU per milliliter of uropathogens

between the UTI and no-UTI cohorts.

Depicted are the average CFU per milliliter with

which the various uropathogens were cultured
for both cohorts: UTI (blue bars) and no-UTI (red
bars).
 Average CFU of Klebsiella pneumoniae (P 0.04)
and Streptococcus agalactiae (P0.02) are
significantly higher in the UTI cohort (*).
Several uropathogens had substantially lower
average CFU-per-milliliter values in the no-UTI
cohort than in the UTI cohort: Aerococcus urinae
(P 0.12), Enterococcus faecalis (P 0.09), Escherichia
coli (P 0.08), Staphylococcus aureus (P 0.06), and
Streptococcus anginosus (P 0.06). Independent t
test (*, P 0.05).
The Clinical Urine Culture: Enhanced Techniques Improve Detection of  Black bars depict common UTI thresholds.
Clinically Relevant Microorganisms. Travis K. Price, Tanaka Dune, Evann E. Hilt, Krystal J.
Thomas-White, Stephanie Kliethermes, Cynthia Brincat, Linda Brubaker, Alan J. Wolfe, Elizabeth R.
Mueller, Paul C. Schreckenbergere.
Journal of Clinical Microbiology May 2016 Volume 54 Number 5
LACTOBACILLUS

 Czaja CA, Stapleton AE,Yarova-Yarovaya Y, Stamm WE (2007) Phase I trial of a Lactobacillus crispatus vaginal
suppository for prevention of recurrent urinary tract infection in women. Infect Dis Obstet Gynecol 2007: 35387.
 Certain Lactobacillus species that colonize the vagina excrete lactic acid and hydrogen peroxide, inhibiting the
growth of uropathogenic E coli.
E. COLI UROPATOGEN (UPEC)

 UTI pain was due to E. coli lipopolysaccharide (LPS) and its receptor, TLR4, but pain was not correlated with
inflammation.
 Inflammatory responses in wild type mice were similar among E. coli strains spanning a wide range of pain
phenotypes, suggesting that O-antigen modulates pain independent of inflammation.
 A UPEC mutant defective for O-antigen biosynthesis induced chronic allodynia that persisted long after
clearance of transient infections,
 Wild type UPEC evoked only acute pain.
 Chronic allodynia was abrogated in TLR4-deficient mice.

Rudick CN, Jiang M,Yaggie RE, Pavlov VI, Done J, et al. (2012) O-Antigen Modulates Infection-Induced Pain States. PLoS ONE 7(8):
e41273. doi:10.1371/journal.pone.0041273
E. COLI ASIMPTOMATIC (ASB)

 ASB E. coli (83972) were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus
faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current
standard of care yet also provide superior analgesia. (1)
 ASB E. coli 2-12 - No LUTS were noted in any of the 6 research dogs after ASB E. coli 2-12 infusion. Four of the
nine client-owned dogs had complete or nearly complete clinical cures by day 14. Of these four dogs, 3 also had
microbiologic cures at day 14; one of these dogs had subclinical bacteriuria (in addition to ASB E. coli 2-12). Three
of these four dogs had ASB E. coli 2-12 isolated from their urine at day 14.

1. Rudick CN,Taylor AK,Yaggie RE, Schaeffer AJ, Klumpp DJ (2014) Asymptomatic Bacteriuria Escherichia coli Are Live
Biotherapeutics for UTI. PLoS ONE 9(11): e109321. doi:10.1371/journal.pone.0109321
2. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli 2-12, in Healthy Dogs and Dogs with
Clinical Recurrent UTI. G. Segev , J.E. Sykes, D.J. Klumpp, A.J. Schaeffer, E.M. Antaki, B.A. Byrne, R.E.Yaggie, and J.L. Westropp. J
Vet Intern Med 2018;32:267–273
PERSPECTIVE CLINICE

 E. coli asimptomatic
 Lactobacil
 Modularea durerii in cistita recidivanta
 Vezica hiperactiva rezistenta la tratament
 Flora vaginala- estrogenizare
 Bacteriuria asimptomatica NU se trateaza antibiotic = UROBIOTA