scholarly journals Strain-dependent inhibition of Clostridioides difficile by commensal Clostridia encoding the bile acid inducible (bai) operon

2020 ◽  
Author(s):  
A.D. Reed ◽  
M.A. Nethery ◽  
A. Stewart ◽  
R. Barrangou ◽  
C.M. Theriot
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Culture System ◽  
Dependent Manner ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
The Relationship ◽  
Strain Dependent ◽  
Secondary Bile Acids

AbstractClostridioides difficile is one of the leading causes of antibiotic-associated diarrhea. Gut microbiota-derived secondary bile acids and commensal Clostridia that encode the bile acid inducible (bai) operon are associated with protection from C. difficile infection (CDI), although the mechanism is not known. In this study we hypothesized that commensal Clostridia are important for providing colonization resistance against C. difficile due to their ability to produce secondary bile acids, as well as potentially competing against C. difficile for similar nutrients. To test this hypothesis, we examined the ability of four commensal Clostridia encoding the bai operon (C. scindens VPI 12708, C. scindens ATCC 35704, C. hiranonis, and C. hylemonae) to convert CA to DCA in vitro, and if the amount of DCA produced was sufficient to inhibit growth of a clinically relevant C. difficile strain. We also investigated the competitive relationship between these commensals and C. difficile using an in vitro co-culture system. We found that inhibition of C. difficile growth by commensal Clostridia supplemented with CA was strain-dependent, correlated with the production of ∼2 mM DCA, and increased expression of bai operon genes. We also found that C. difficile was able to outcompete all four commensal Clostridia in an in vitro co-culture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics. Future studies dissecting the regulation of the bai operon in vitro and in vivo and how this affects CDI will be important.ImportanceCommensal Clostridia encoding the bai operon such as C. scindens have been associated with protection against CDI, however the mechanism for this protection is unknown. Herein, we show four commensal Clostridia that encode the bai operon effect C. difficile growth in a strain-dependent manner, with and without the addition of cholate. Inhibition of C. difficile by commensals correlated with the efficient conversion of cholate to deoxycholate, a secondary bile acid that inhibits C. difficile germination, growth, and toxin production. Competition studies also revealed that C. difficile was able to outcompete the commensals in an in vitro co-culture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics.

scholarly journals Strain-Dependent Inhibition of Clostridioides difficile by Commensal Clostridia Carrying the Bile Acid-Inducible (bai) Operon

2020 ◽  
Vol 202 (11) ◽  
Author(s):  
A. D. Reed ◽  
M. A. Nethery ◽  
A. Stewart ◽  
R. Barrangou ◽  
C. M. Theriot
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Dependent Manner ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Coculture System ◽  
The Relationship ◽  
Strain Dependent ◽  
Secondary Bile Acids

ABSTRACT Clostridioides difficile is one of the leading causes of antibiotic-associated diarrhea. Gut microbiota-derived secondary bile acids and commensal Clostridia that carry the bile acid-inducible (bai) operon are associated with protection from C. difficile infection (CDI), although the mechanism is not known. In this study, we hypothesized that commensal Clostridia are important for providing colonization resistance against C. difficile due to their ability to produce secondary bile acids, as well as potentially competing against C. difficile for similar nutrients. To test this hypothesis, we examined the abilities of four commensal Clostridia carrying the bai operon (Clostridium scindens VPI 12708, C. scindens ATCC 35704, Clostridium hiranonis, and Clostridium hylemonae) to convert cholate (CA) to deoxycholate (DCA) in vitro, and we determined whether the amount of DCA produced was sufficient to inhibit the growth of a clinically relevant C. difficile strain. We also investigated the competitive relationships between these commensals and C. difficile using an in vitro coculture system. We found that inhibition of C. difficile growth by commensal Clostridia supplemented with CA was strain dependent, correlated with the production of ∼2 mM DCA, and increased the expression of bai operon genes. We also found that C. difficile was able to outcompete all four commensal Clostridia in an in vitro coculture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics. Future studies dissecting the regulation of the bai operon in vitro and in vivo and how this affects CDI will be important. IMPORTANCE Commensal Clostridia carrying the bai operon, such as C. scindens, have been associated with protection against CDI; however, the mechanism for this protection is unknown. Herein, we show four commensal Clostridia that carry the bai operon and affect C. difficile growth in a strain-dependent manner, with and without the addition of cholate. Inhibition of C. difficile by commensals correlated with the efficient conversion of cholate to deoxycholate, a secondary bile acid that inhibits C. difficile germination, growth, and toxin production. Competition studies also revealed that C. difficile was able to outcompete the commensals in an in vitro coculture system. These studies are instrumental in understanding the relationship between commensal Clostridia and C. difficile in the gut, which is vital for designing targeted bacterial therapeutics.

Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians

2020 ◽  
Author(s):  
Kenya Honda ◽  
Yuko Sato ◽  
Koji Atarashi ◽  
Damian Plichta ◽  
Yasumichi Arai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Lithocholic Acid ◽  
Multidrug Resistant ◽  
Bile Acid Metabolism ◽  
Critical Determinant ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Vancomycin Resistant ◽  
Secondary Bile Acids

Abstract Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified Parabacteroides merdae and Odoribacteraceae strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of P. merdae to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and vancomycin-resistant Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.

scholarly journals Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine

mSphere ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Casey M. Theriot ◽  
Alison A. Bowman ◽  
Vincent B. Young
Keyword(s):  
Bile Acid ◽  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Large Intestine ◽  
Spore Germination ◽  
Secondary Bile Acid ◽  
Content Type ◽  
Secondary Bile Acids

ABSTRACT Antibiotics alter the gastrointestinal microbiota, allowing for Clostridium difficile infection, which is a significant public health problem. Changes in the structure of the gut microbiota alter the metabolome, specifically the production of secondary bile acids. Specific bile acids are able to initiate C. difficile spore germination and also inhibit C. difficile growth in vitro, although no study to date has defined physiologically relevant bile acids in the gastrointestinal tract. In this study, we define the bile acids C. difficile spores encounter in the small and large intestines before and after various antibiotic treatments. Antibiotics that alter the gut microbiota and deplete secondary bile acid production allow C. difficile colonization, representing a mechanism of colonization resistance. Multiple secondary bile acids in the large intestine were able to inhibit C. difficile spore germination and growth at physiological concentrations and represent new targets to combat C. difficile in the large intestine. It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes. IMPORTANCE Antibiotics alter the gastrointestinal microbiota, allowing for Clostridium difficile infection, which is a significant public health problem. Changes in the structure of the gut microbiota alter the metabolome, specifically the production of secondary bile acids. Specific bile acids are able to initiate C. difficile spore germination and also inhibit C. difficile growth in vitro, although no study to date has defined physiologically relevant bile acids in the gastrointestinal tract. In this study, we define the bile acids C. difficile spores encounter in the small and large intestines before and after various antibiotic treatments. Antibiotics that alter the gut microbiota and deplete secondary bile acid production allow C. difficile colonization, representing a mechanism of colonization resistance. Multiple secondary bile acids in the large intestine were able to inhibit C. difficile spore germination and growth at physiological concentrations and represent new targets to combat C. difficile in the large intestine.

scholarly journals 2567. Effect of Broad vs. Narrow-Spectrum Clostridioides difficile Treatment on Human Stool Bile Acid Composition Over Time

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S891-S891
Author(s):  
Cheleste M Thorpe ◽  
Xi Qian ◽  
Karin Yanagi ◽  
Anne Kane ◽  
Nicholas Alden ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Composition ◽  
Critical Factor ◽  
Acid Synthesis ◽  
Secondary Bile Acid ◽  
Narrow Spectrum ◽  
Commensal Flora ◽  
Clostridioides Difficile ◽  
Secondary Bile Acids

Abstract Background Secondary bile acid production by a diverse commensal flora may be a critical factor in preventing recurrence of Clostridioides difficile infection (CDI). Key enzymes involved are bacterial-encoded bile salt hydrolases (BSHs), felt to be “gatekeepers” to secondary bile acid synthesis. Ridinilazole, a novel narrow-spectrum drug for CDI, demonstrated superior sustained clinical response compared with vancomycin in Phase 2. Longitudinal sampling during this trial allowed for assessment of metabolites differentially present in stools during/after therapy with either broad or narrow-spectrum anti-CDI agent. Previous work characterizing subject’s fecal microbiota in this trial showed that unlike vancomycin, ridinilazole has little effect on commensal flora during and after therapy. We hypothesized that ridinilazole’s microbiota-preserving effect is associated with lack of accumulation of conjugated primary bile acids and/or reaccumulation/persistence of secondary bile acids over the course of CDI treatment, when compared with vancomycin-treated subjects. Furthermore, we hypothesized that we would observe correlations between bile acid profiles and predicted BSH gene abundances. Methods Sequential stool samples were obtained from 44 subjects treated with either ridinilazole or vancomycin (22 in each arm), ranging from time of CDI diagnosis, at end-of-therapy, and up to 40 days after diagnosis. Bile acids were quantitated by liquid chromatography-mass spectrometry. Using the PICRUSt algorithm, metagenomic predictions of BSH gene abundances were performed. Results Stool bile acid compositions differed between ridinilazole-treated and vancomycin-treated subjects at end-of-therapy. In vancomycin-treated subjects, stool composition became dominated by conjugated primary bile acids and decreased levels of secondary bile acids compared with baseline; the ratio of stool conjugated bile acids to secondary bile acids significantly predicted treatment arm. This ratio was also associated with predicted BSH gene abundance in ridinilazole-treated subjects. Conclusion Microbiota-preserving CDI treatment with ridinilazole preserves bile acid composition, which may decrease likelihood of recurrence. Disclosures All authors: No reported disclosures.

scholarly journals 2′FL and LNnT Exert Antipathogenic Effects against C. difficile ATCC 9689 In Vitro, Coinciding with Increased Levels of Bifidobacteriaceae and/or Secondary Bile Acids

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 927
Author(s):  
Louise Kristine Vigsnaes ◽  
Jonas Ghyselinck ◽  
Pieter Van den Van den Abbeele ◽  
Bruce McConnell ◽  
Frédéric Moens ◽  
...  
Keyword(s):  
Antimicrobial Effect ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Life Threatening ◽  
Intermediate Time ◽  
Indigenous Microbiota ◽  
Hospital Acquired ◽  
Gut Microbial Community ◽  
Secondary Bile Acids

Clostridioides difficile (formerly Clostridium difficile) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the antipathogenic potential of human milk oligosaccharides (HMOs), i.e., 2′-O-fucosyllactose (2′FL), lacto-N-neotetraose (LNnT), and a combination thereof (MIX), against C. difficile ATCC 9689 using in vitro gut models that allowed the evaluation of both direct and, upon microbiota modulation, indirect effects. During a first 48 h fecal batch study, dysbiosis and CDI were induced by dilution of the fecal inoculum. For each of the three donors tested, C. difficile levels strongly decreased (with >4 log CFU/mL) upon treatment with 2′FL, LNnT and MIX versus untreated blanks, coinciding with increased acetate/Bifidobacteriaceae levels. Interindividual differences among donors at an intermediate time point suggested that the antimicrobial effect was microbiota-mediated rather than being a direct effect of the HMOs. During a subsequent 11 week study with the PathogutTM model (specific application of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®)), dysbiosis and CDI were induced by clindamycin (CLI) treatment. Vancomycin (VNC) treatment cured CDI, but the further dysbiosis of the indigenous microbiota likely contributed to CDI recurrence. Upon co-supplementation with VNC, both 2′FL and MIX boosted microbial activity (acetate and to lesser extent propionate/butyrate). Moreover, 2′FL avoided CDI recurrence, potentially because of increased secondary bile acid production. Overall, while not elucidating the exact antipathogenic mechanisms-of-action, the current study highlights the potential of HMOs to combat CDI recurrence, help the gut microbial community recover after antibiotic treatment, and hence counteract the adverse effects of antibiotic therapies.

An aniline-substituted bile salt analog protects both mice and hamsters from multiple Clostridioides difficile strains

2021 ◽  
Author(s):  
Jacqueline R. Phan ◽  
Dung M. Do ◽  
Minh Chau Truong ◽  
Connie Ngo ◽  
Julian H. Phan ◽  
...  
Keyword(s):  
Bile Salt ◽  
Spore Germination ◽  
Dependent Manner ◽  
Germination Inhibitors ◽  
New Methods ◽  
Clostridioides Difficile ◽  
Antibiotic Associated Diarrhea ◽  
Careful Screening ◽  
Strain Dependent

Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea. The emergence of hypervirulent C. difficile strains has led to increases in both hospital- and community-acquired CDI. Furthermore, CDI relapse from hypervirulent strains can reach up to 25%. Thus, standard treatments are rendered less effective, making new methods of prevention and treatment more critical. Previously, the bile salt analog CamSA was shown to inhibit spore germination in vitro and protect mice and hamsters from C. difficile strain 630. Here, we show that CamSA was less active at preventing spore germination of other C. difficile ribotypes, including the hypervirulent strain R20291. Strain-specific in vitro germination activity of CamSA correlated with its ability to prevent CDI in mice. Additional bile salt analogs were screened for in vitro germination inhibition activity against strain R20291, and the most active compounds were tested against other strains. An aniline-substituted bile salt analog, (CaPA), was found to be a better anti-germinant than CamSA against eight different C. difficile strains. In addition, CaPA was capable of reducing, delaying, or preventing murine CDI signs in all strains tested. CaPA-treated mice showed no obvious toxicity and showed minor effects on their gut microbiome. CaPA’s efficacy was further confirmed by its ability to prevent CDI in hamsters infected with strain 630. These data suggest that C. difficile spores respond to germination inhibitors in a strain-dependent manner. However, careful screening can identify anti-germinants with broad CDI prophylaxis activity.

scholarly journals Bile acid metabolism is altered in multiple sclerosis and supplementation ameliorates neuroinflammation

2019 ◽  
Author(s):  
Pavan Bhargava ◽  
Leah Mische ◽  
Matthew D. Smith ◽  
Emily Harrington ◽  
Kathryn C Fitzgerald ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
White Matter Lesions ◽  
The Body ◽  
Bile Acid Metabolism ◽  
Dependent Manner ◽  
Microglial Polarization

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. Bile acids are cholesterol metabolites that can signal through receptors on cells throughout the body, including the CNS and immune system. Whether bile acid metabolism is abnormal in MS is unknown. Using global and targeted metabolomic profiling, we identified lower levels of circulating bile acid metabolites in multiple cohorts of adult and pediatric MS patients compared to controls. In white matter lesions from MS brain tissue, we noted the presence of bile acid receptors on immune and glial cells. To mechanistically examine the implications of lower levels of bile acids in MS, we studied the in vitro effects of an endogenous bile acid – tauroursodeoxycholic acid (TUDCA) on astrocyte and microglial polarization. TUDCA prevented neurotoxic (A1) polarization of astrocytes and pro-inflammatory polarization of microglia in a dose-dependent manner. TUDCA supplementation in experimental autoimmune encephalomyelitis reduced severity of disease, based on behavioral and pathological measures. We demonstrate that bile acid metabolism is altered in MS; bile acid supplementation prevents polarization of astrocytes and microglia to neurotoxic phenotypes and ameliorates neuropathology in an animal model of MS. These findings identify dysregulated bile acid metabolism as a potential therapeutic target in MS.

scholarly journals In Vitro Interactions of Dietary Fibre Enriched Food Ingredients with Primary and Secondary Bile Acids

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1424 ◽  
Author(s):  
Susanne Naumann ◽  
Ute Schweiggert-Weisz ◽  
Julia Eglmeier ◽  
Dirk Haller ◽  
Peter Eisner
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Dietary Fibre ◽  
In Vitro Digestion ◽  
Food Ingredients ◽  
Bile Acid Pool Size ◽  
As Adsorption ◽  
Secondary Bile Acids ◽  
In Vitro Interactions

Dietary fibres are reported to interact with bile acids, preventing their reabsorption and promoting their excretion into the colon. We used a method based on in vitro digestion, dialysis, and kinetic analysis to investigate how dietary fibre enriched food ingredients affect the release of primary and secondary bile acids as related to viscosity and adsorption. As the main bile acids abundant in humans interactions with glyco- and tauroconjugated cholic acid, chenodesoxycholic acid and desoxycholic acid were analysed. Viscous interactions were detected for apple, barley, citrus, lupin, pea, and potato derived ingredients, which slowed the bile acid release rate by up to 80%. Adsorptive interactions of up to 4.7 μmol/100 mg DM were significant in barley, oat, lupin, and maize preparations. As adsorption directly correlated to the hydrophobicity of the bile acids the hypothesis of a hydrophobic linkage between bile acids and dietary fibre is supported. Delayed diffusion in viscous fibre matrices was further associated with the micellar properties of the bile acids. As our results indicate changes in the bile acid pool size and composition due to interactions with dietary fibre rich ingredients, the presented method and results could add to recent fields of bile acid research.

scholarly journals Temporal Fluctuations of Gut Microbiota and Bile Acid Metabolism in Critically Ill Children

2021 ◽  
Author(s):  
Iain Robert Louis Kean ◽  
Josef Wagner ◽  
Anisha Wijeyesekera ◽  
Marcus de Goffau ◽  
Sarah Thurston ◽  
...  
Keyword(s):  
Bile Acid ◽  
Critical Illness ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Critically Ill ◽  
Critically Ill Children ◽  
Bile Acid Metabolism ◽  
Rrna Gene ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids

Abstract Background: Critical illness frequently requires the use of broad-spectrum antimicrobials to treat life-threatening infection. The resulting impact on microbiome diversity is profound, influencing gastrointestinal fermentation endpoints, host immune response and metabolic activity including the conversion of primary bile acids to secondary bile acids. We previously observed reduced fermentation capacity in the gut microbiota of critically ill children upon hospital admission, but the functional recovery trajectory of the paediatric gut microbiome during critical illness has not been well defined. Here, we longitudinally studied the intestinal microbiome and faecal bile acid profile of critically ill children during hospitalisation in a paediatric intensive care unit (PICU). The composition of the microbiome was determined by sequencing of the 16s rRNA gene, and bile acids were measured from faecal water by liquid chromatography hyphenated to mass spectrometry. Results: In comparison to admission faecal samples, members of Clostridium cluster XIVa and Lachnospiraceae recovered during the late-acute phase (days 8-10) of hospitalisation. Patients with infections had a lower proportion of Lachnospiraceae in their gut microbiota than control microbiota and patients with admitting diagnoses. The proportion of Recovery Associated Bacteria (RAB) was observed to decline with the length of PICU admission. Additionally, the proportions of RAB were reduced in those with systemic infection, respiratory failure, and undergoing surgery. Notably, Clostridioides were positively associated with the secondary bile acid deoxycholic acid, which we hypothesised to driven by secondary bile acid induced sporulation; the ratio of primary to secondary bile acids demonstrated recovery during critical illness. Conclusion: The recovery of secondary bile acids occurs quickly after intervention for critical illness. Bile acid recovery may be induced by the Lachnospiraceae , the composition of which shifts during critical illness. Our data suggest that gut health and early gut microbiota recovery can be assessed by readily quantifiable faecal bile acid profiles.

scholarly journals The influence of probiotics on individual fecal secondary bile acid levels: a two-case study of schizophrenic patients receiving an atypical antipsychotic drug

2017 ◽  
Vol 7 (11) ◽  
pp. 849
Author(s):  
Yosuke Saito ◽  
Hiroyuki Nishimiya ◽  
Yasue Kondo ◽  
Toyoaki Sagae
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Bile Salt Hydrolase ◽  
Atypical Antipsychotic Drug ◽  
Secondary Bile Acid ◽  
Secondary Bile Acids ◽  
Bsh Activity

Background: Probiotics is used as a promising approach in the prevention and treatment of hypercholesterolemia. Modification of bile acid metabolism through the deconjugation of bile salts by microbial bile salt hydrolase (BSH) is considered to be the core mechanism of the hypocholesterolemic effects of probiotics. Nevertheless, BSH activity is reported to be detrimental to the human host due to the generation of toxic secondary bile acids. Thus, the influence of probiotic intake on bile acid metabolism needs to be elucidated. We analyzed the bile acid levels and microbiota in human fecal samples after probiotic supplementation to assess the influence of probiotic intake on fecal bile acid levels. Two patients hospitalized for schizophrenia and dyslipidemia, receiving an atypical antipsychotic drug, were enrolled in this study (Subjects A and B). Both subjects received Lactobacillus rhamnosus GG (LGG) for 4 weeks, and no probiotics for the following 4 weeks. Fecal samples were collected at baseline and after 4 and 8 weeks.Results: Conjugated bile acids may be modified by indigenous intestinal bacteria into unconjugated bile acids and secondary bile acids through deconjugation reactions by BSH activity and the subsequent 7a-dehydroxylation pathway, respectively. In the fecal microbiota from Subject A, the relative abundance of Bifidobacterium increased after LGG supplementation (30%–49%). Most Bifidobacterium and Lactobacillus strains that colonize mammalian intestines may report BSH activity, and in general bifidobacteria reveals a higher BSH activity than lactobacilli. The fecal unconjugated bile acid and secondary bile acid levels in Subject A increased after the LGG supplementation (0.36–1.79 and 1.82–16.19 mmol/g respectively). Although the LGG supplementation appears to promote bile acid deconjugation, most of the unconjugated bile acids in Subject A appear to have been modified into secondary bile acids. Alternatively, in Subject B there were no significant changes throughout the study.Conclusion: We observed a significant increase in the fecal secondary bile acid levels after probiotic administration in one of our cases. Further studies are needed to elucidate the factors affecting 7a-dehydroxylation of bile acids to confirm the safety of using probiotics.Keywords: bile salt hydrolase; BSH; dihydroxylation; Bifidobacterium

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