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Gut microbiome is crucial for lipid metabolism in humans and animals. However, how specific gut microbiota and their associated metabolites impact fat deposition remains unclear. In this study, we demonstrated that the colonic microbiome of lean and obese pigs differentially contributes to fat deposition, as evidenced by colonic microbiota transplantation experiments. Notably, the higher abundance of Bifidobacterium pseudocatenulatum was significantly associated with lower backfat thickness in lean pigs. Microbial‐derived lithocholic acid (LCA) species were also significantly enriched in lean pigs and positively correlated with the abundance of B. pseudocatenulatum. In a high‐fat diet (HFD)‐fed mice model, administration of live B. pseudocatenulatum decreased fat deposition and enhances colonic secondary bile acid biosynthesis. Importantly, pharmacological inhibition of the bile salt hydrolase (BSH), which mediates secondary bile acid biosynthesis, impaired the anti‐fat deposition effect of B. pseudocatenulatum in antibiotic‐pretreated, HFD‐fed mice. Furthermore, dietary LCA also decreased fat deposition in HFD‐fed rats and obese pig models. These findings provide mechanistic insights into the anti‐fat deposition role of B. pseudocatenulatum and identify BSH as a potential target for preventing excessive fat deposition in humans and animals. Highlights: The gut microbiota composition and function differ significantly between lean and obese pigs, and breed‐specific microbiomes regulate fat deposition.Gut Bifidobacterium pseudocatenulatum protects against fat deposition by enhancing secondary bile acid biosynthesis.Dietary supplementation with lithocholic acid also helps prevent fat deposition. [ABSTRACT FROM AUTHOR]

Abstract Background Metabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear. Aim of the study This study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism. Methods High-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment. Results ZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver. Conclusion Our study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY.

Background: Metabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear. Aim of the study: This study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism. Methods: High-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment. Results: ZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver. Conclusion: Our study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY. [ABSTRACT FROM AUTHOR]

This study aimed to select Lactobacillus with high bile salt hydrolase (BSH) and to explore its protective role against neonatal jaundice. The LBS selective medium supplemented with 25 U/mL nystatin was used to screen and identify Lactobacillus strains isolated from the feces of healthy newborns and breast milk. L. rhamnosus (LGG) was used as a positive control to evaluate the in vitro probiotic properties and bile salt hydrolase activity of the Lactobacillus strains. Thereafter, the protective effect and mechanism of the selected isolates with high bile salt hydrolase activity against phenylhydrazine hydrochloride (PHZ)-induced neonatal jaundice in rats were investigated by analyzing serum bilirubin levels, hepatotoxicity, and the expression of inflammatory cytokines and nuclear transcription factors in the liver. The results showed that compared with the LGG, L. gasseri FWJL-5, which was isolated from infant feces, exhibited outstanding in vitro probiotic properties and higher bile salt hydrolase activity than LGG. L. gasseri FWJL-5 significantly alleviated the increase in serum bilirubin levels, liver tissue swelling and hemolysis in PHZ-treated neonatal rats, reduced the release of hepatic enzymes, inhibited the secretion of proinflammatory cytokines, and promoted the expression of UGT1A1, pregnane X receptor (PXR), and farnesol X receptor (FXR). Taken together, L. gasseri FWJL-5 could regulate bilirubin metabolism in the liver by up-regulating the expression of FXR/PXR and UGT1A1, thereby alleviating neonatal jaundice in rats. Our findings may provide new ideas for the prevention and treatment of neonatal jaundice by L. gasseri.

Although the liver is the largest metabolic organ in the body, it is not alone in functionality and is assisted by "an organ inside an organ," the gut microbiota. This review attempts to shed light on the partnership between the liver and the gut microbiota in the metabolism of macronutrients (i.e., proteins, carbohydrates, and lipids). All nutrients absorbed by the small intestines are delivered to the liver for further metabolism. Undigested food that enters the colon is metabolized further by the gut microbiota that produces secondary metabolites, which are absorbed into portal circulation and reach the liver. These microbiota‐derived metabolites and co‐metabolites include ammonia, hydrogen sulfide, short‐chain fatty acids, secondary bile acids, and trimethylamine N‐oxide. Further, the liver produces several compounds, such as bile acids that can alter the gut microbial composition, which can in turn influence liver health. This review focuses on the metabolism of these microbiota metabolites and their influence on host physiology. Furthermore, the review briefly delineates the effect of the portosystemic shunt on the gut microbiota–liver axis, and current understanding of the treatments to target the gut microbiota–liver axis. [ABSTRACT FROM AUTHOR]

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Clostridium perfringens is the main pathogen of chicken necrotic enteritis (NE) causing huge economic losses in the poultry industry. Although dietary secondary bile acid deoxycholic acid (DCA) reduced chicken NE, the accumulation of conjugated tauro-DCA (TDCA) raised concerns regarding DCA efficacy. In this study, we aimed to deconjugate TDCA by bile salt hydrolase (BSH) to increase DCA efficacy against the NE pathogen C. perfringens. Assays were conducted to evaluate the inhibition of C. perfringens growth, hydrogen sulfide (H2S) production, and virulence gene expression by TDCA and DCA. BSH activity and sequence alignment were conducted to select the bsh gene for cloning. The bsh gene from Bifidobacterium longum was PCR-amplified and cloned into plasmids pET-28a (pET-BSH) and pDR111 (pDR-BSH) for expressing the BSH protein in E. coli BL21 and Bacillus subtilis 168 (B-sub-BSH), respectively. His-tag-purified BSH from BL21 cells was evaluated by SDS-PAGE, Coomassie blue staining, and a Western blot (WB) assays. Secretory BSH from B. subtilis was analyzed by a Dot-Blot. B-sub-BSH was evaluated for the inhibition of C. perfringens growth. C. perfringens growth reached 7.8 log10 CFU/mL after 24 h culture. C. perfringens growth was at 8 vs. 7.4, 7.8 vs. 2.6 and 6 vs. 0 log10 CFU/mL in 0.2, 0.5, and 1 mM TDCA vs. DCA, respectively. Compared to TDCA, DCA reduced C. perfringens H2S production and the virulence gene expression of asrA1, netB, colA, and virT. BSH activity was observed in Lactobacillus johnsonii and B. longum under anaerobe but not L. johnsonii under 10% CO2 air. After the sequence alignment of bsh from ten bacteria, bsh from B. longum was selected, cloned into pET-BSH, and sequenced at 951 bp. After pET-BSH was transformed in BL21, BSH expression was assessed around 35 kDa using Coomassie staining and verified for His-tag using WB. After the subcloned bsh and amylase signal peptide sequence was inserted into pDR-BSH, B. subtilis was transformed and named B-sub-BSH. The transformation was evaluated using PCR with B. subtilis around 3 kb and B-sub-BSH around 5 kb. Secretory BSH expressed from B-sub-BSH was determined for His-tag using Dot-Blot. Importantly, C. perfringens growth was reduced greater than 59% log10 CFU/mL in the B-sub-BSH media precultured with 1 vs. 0 mM TDCA. In conclusion, TDCA was less potent than DCA against C. perfringens virulence, and recombinant secretory BSH from B-sub-BSH reduced C. perfringens growth, suggesting a new potential intervention against the pathogen-induced chicken NE. [ABSTRACT FROM AUTHOR]

Bile Salt Hydrolase (BSH) is a bacterial enzyme (EC 3.5.1.24) that initiates the crucial deconjugation of bile acids (BAs), a process necessary for their transformation into secondary BAs by gut microbes. Recent advance has delved deeper into BAs, recognizing them as endocrine molecules capable of modulating lipid and sugar metabolism in the host.In this review, we elucidate how this wealth of research has broadened our understanding about the intricate mechanisms between BAs and the gut microbiota beyond BSH, underlying the hypocholesterolemic effects of probiotic lactobacilli. We highlight the expanded range of various species of lactobacilli with proven cholesterol-lowering activity both in vitro and in vivo associated with BSH activity. In addition, a summary of genomic and metagenomic studies investigating bsh genes in both gut microbiota and lactobacilli is provided, to be used as an additional tool for the selection of a potential lactobacilli probiotic.

Simple Summary: This review explores the emergence of new literature connecting microbial-derived bile acid metabolism to canine and feline health and disease. Specifically, it highlights how gut microbes can orchestrate canine and feline physiology and disease through metabolism and the diversification of bile acid pools, which ultimately impact the host via the activation of bile acid receptors. Incorporating the therapeutic potential of bile acid metabolism into evidence-based veterinary practice will require familiarity with and an understanding of these concepts for a broad array of veterinarians including general practitioners, specialists, and researchers. Bile acids, produced by the liver and secreted into the gastrointestinal tract, are dynamic molecules capable of impacting the overall health of dogs and cats in many contexts. Importantly, the gut microbiota metabolizes host primary bile acids into chemically distinct secondary bile acids. This review explores the emergence of new literature connecting microbial-derived bile acid metabolism to canine and feline health and disease. Moreover, this review highlights multi-omic methodologies for translational research as an area for continued growth in veterinary medicine aimed at accelerating microbiome science and medicine as it pertains to bile acid metabolism in dogs and cats. [ABSTRACT FROM AUTHOR]

Background & Aims: A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB. Methods: To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed. Results: Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination. Conclusions: R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.

Background. One of the mechanisms of the of irritable bowel syndrome with diarrhea (IBS-D) is bile acid malabsorption (BAM). In addition to the use of bile acid sequestrants, probiotic bacteria synthesizing bile salt hydrolase (BSH) are promising in the treatment of probable BAM. The purpose of the study was to compare the effectiveness of combined treatment (a probiotic based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii and cholestyramine) with cholestyramine monotherapy in the treatment of IBS-D. Materials and methods. A 12-week randomized study included 108 patients with IBS-D divided into a control group (n = 51) receiving only cholestyra­mine and an experimental group (n = 57) receiving a combination of cholestyramine and the study probiotic. At baseline, the relative activity of BSH of the study probiotic capsules was determined. During the stages of the study, patients were examined using clinical scales. Results. The relative activity of BSH of the capsules with the studied probiotic was (2.07 ± 0.06) U/ml compared to (1.00 ± 0.04) U/ml of capsules with L.plantarum and (0.03 ± 0.01) U/ml — with L.plantarum without BSH genes. In the experimental group, the severity of bloating and visceral sensitivity index were lower after 8 and 12 weeks, and the value of the stool type according to the Bristol scale and its daily frequency — after 12 weeks compared to the control group, p < 0.05. According to the scale of IBS-adequate relief, the percentage of achieving a clinical effect was higher in the experimental group compared to the controls after 12 weeks, odds ratio was 1.31 (95% confidence interval 1.03–1.68), p = 0.038. Conclusions. Additional prescription of a probiotic with BSH synthesizing bacterial strains is more effective in improving clinical manifestations of IBS-D and achieving a therapeutic effect compared to cholestyramine monotherapy.

Clostridium perfringens is the main pathogen of chicken necrotic enteritis (NE) causing huge economic losses in the poultry industry. Although dietary secondary bile acid deoxycholic acid (DCA) reduced chicken NE, the accumulation of conjugated tauro-DCA (TDCA) raised concerns regarding DCA efficacy. In this study, we aimed to deconjugate TDCA by bile salt hydrolase (BSH) to increase DCA efficacy against the NE pathogen C. perfringens. Assays were conducted to evaluate the inhibition of C. perfringens growth, hydrogen sulfide (H2S) production, and virulence gene expression by TDCA and DCA. BSH activity and sequence alignment were conducted to select the bsh gene for cloning. The bsh gene from Bifidobacterium longum was PCR-amplified and cloned into plasmids pET-28a (pET-BSH) and pDR111 (pDR-BSH) for expressing the BSH protein in E. coli BL21 and Bacillus subtilis 168 (B-sub-BSH), respectively. His-tag-purified BSH from BL21 cells was evaluated by SDS-PAGE, Coomassie blue staining, and a Western blot (WB) assays. Secretory BSH from B. subtilis was analyzed by a Dot-Blot. B-sub-BSH was evaluated for the inhibition of C. perfringens growth. C. perfringens growth reached 7.8 log10 CFU/mL after 24 h culture. C. perfringens growth was at 8 vs. 7.4, 7.8 vs. 2.6 and 6 vs. 0 log10 CFU/mL in 0.2, 0.5, and 1 mM TDCA vs. DCA, respectively. Compared to TDCA, DCA reduced C. perfringens H2S production and the virulence gene expression of asrA1, netB, colA, and virT. BSH activity was observed in Lactobacillus johnsonii and B. longum under anaerobe but not L. johnsonii under 10% CO2 air. After the sequence alignment of bsh from ten bacteria, bsh from B. longum was selected, cloned into pET-BSH, and sequenced at 951 bp. After pET-BSH was transformed in BL21, BSH expression was assessed around 35 kDa using Coomassie staining and verified for His-tag using WB. After the subcloned bsh and amylase signal peptide sequence was inserted into pDR-BSH, B. subtilis was transformed and named B-sub-BSH. The transformation was evaluated using PCR with B. subtilis around 3 kb and B-sub-BSH around 5 kb. Secretory BSH expressed from B-sub-BSH was determined for His-tag using Dot-Blot. Importantly, C. perfringens growth was reduced greater than 59% log10 CFU/mL in the B-sub-BSH media precultured with 1 vs. 0 mM TDCA. In conclusion, TDCA was less potent than DCA against C. perfringens virulence, and recombinant secretory BSH from B-sub-BSH reduced C. perfringens growth, suggesting a new potential intervention against the pathogen-induced chicken NE.

ABSTRACT Bacteroides thetaiotaomicron (B. theta) is a Gram-negative gut bacterium that encodes enzymes that alter the bile acid pool in the gut. Primary bile acids are synthesized by the host liver and are modified by gut bacteria. B. theta encodes two bile salt hydrolases, as well as a hydroxysteroid dehydrogenase. We hypothesize that B. theta modifies the bile acid pool in the gut to provide a fitness advantage for itself. To investigate each gene’s role, different combinations of genes encoding bile acid-altering enzymes (bshA, bshB, and hsdhA) were knocked out by allelic exchange, including a triple KO. Bacterial growth and membrane integrity assays were done in the presence and absence of bile acids. To explore if B. theta’s response to nutrient limitation changes due to the presence of bile acid-altering enzymes, RNA sequencing (RNASeq) analysis of wild type (WT) and triple knockout (KO) strains in the presence and absence of bile acids was done. WT B. theta is more sensitive to deconjugated bile acids such as cholate, chenodeoxycholate (CDCA), and deoxycholate (DCA) compared with the triple KO. These deconjugated bile acids also decreased membrane integrity of both WT and triple KO. The presence of bshB is detrimental to growth in conjugated forms of CDCA and DCA. RNASeq analysis also showed that bile acid exposure impacts multiple metabolic pathways in B. theta, but DCA significantly increases expression of many genes in carbohydrate metabolism, specifically those in polysaccharide utilization loci or PULs, in nutrient-limited conditions. This study suggests that bile acids B. theta encounters in the gut may signal the bacterium to increase or decrease its utilization of carbohydrates. Further study looking at the interactions between bacteria, bile acids, and the host may inform rationally designed probiotics and diets to ameliorate inflammation and disease. IMPORTANCE Recent work on bile salt hydrolases (BSHs) in Gram-negative bacteria, such as Bacteroides, has primarily focused on how they can impact host physiology. However, the benefits bile acid metabolism confers to the bacterium that performs it are not well understood. In this study, we set out to define if and how Bacteroides thetaiotaomicron (B. theta) uses its BSHs and hydroxysteroid dehydrogenase to modify bile acids to provide a fitness advantage for itself in vitro and in vivo. Genes encoding bile acid-altering enzymes were able to impact how B. theta responds to nutrient limitation in the presence of bile acids, specifically carbohydrate metabolism, affecting many polysaccharide utilization loci. This suggests that B. theta may be able to shift its metabolism, specifically its ability to target different complex glycans including host mucin, when it comes into contact with specific bile acids in the gut.

Abstract The increasing interest in functional foods has encouraged the search for new lactic acid bacteria (LAB) with singular characteristics, including technological and probiotic properties, present in natural sources. The present research aimed to isolate and in vitro characterize the probiotic potential of LAB isolated from artisanal goat cheese. In addition, the acidifying and proteolytic capacity of the strains were evaluated in order to develop a functional dairy product. Fifty strains, presumptively identified as LAB, were isolated from artisanal goat cheese. From them, seventeen strains were selected for identification through Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF) Mass Spectrometry (MS) and 16S gene sequence. None of the tested strains showed hemolytic ability, while all strains showed at least 76% of survival to low pH and conjugated bile salts. Hydrophobicity and auto-aggregation values varied among LAB with ranges between 15.5 ± 1.8 to 84.7 ± 3.2, and 4.72% to 59.2%, respectively. Selected LAB were capable of adhering to intestinal mucus in a range of 5.08 to 6.90 Log CFU/mL. Remarkably, eight strains showed high bile salt hydrolase activity. Autochthons strains were able to grow and acidify milk after 24 h. Besides, proteolytic activity showed a range between 10 and 151 mmol/L amino acids. PCA analysis and technological properties allow us to propose Lactiplantibacillus plantarum CB5, CB8 and Lentilactobacillus parabuchneri CB12 strains as potential probiotic starter cultures. The isolation of new LAB strains with demonstrated functional properties is of interest to academic institutions and the food industry as it allows the design of indigenous dairy cultures with added probiotic and technological properties.

One of the benefits of probiotics is reduction of cholesterol by bile salt hydrolase (BSH) enzyme. This study aims to investigate the BSH activity of probiotics derived from fermented foods and to investigate the potential use of selected isolates in fermented dairy products. In this study, 55 isolates of lactic acid bacteria (LAB) were evaluated for their potential BSH activity. Three isolates identified as Lactiplantibacillus paraplantarum MN, Lactiplantibacillus plantarum MN2 and Lactobacillus gasseri SM were selected for their strong BSH activity. All three strains exhibited resistance to pH 3.0 and 4.0 with the number of survival cells around 7.8 and 8.1 log CFU/ml, respectively. They also survived in bile concentration of 0.3% and 0.8% and possessed moderate hydrophobicity. The selected strains and the mixed of three strains at ratio 1:1:1 were used in the production of fermented milk products. All strains and the mixture of three could maintain BSH activity in fermented milk products and survived throughout the storage duration of 28 days. With the properties of good probiotics, these strains could be potentially used in functional dairy products with cholesterol reduction property.

We studied whether probiotics were beneficial for hormonal change-associated dysbiosis, which may influence the enteric nervous system and GI function during early pregnancy. The study was 16 days consisting of two cycles of six daily probiotics mainly Lactobacillus and 2 days without probiotics. Daily surveys were conducted to monitor GI function and life quality. A subset of the participants who contributed fecal specimens was used for microbiota metagenomic sequencing, metabolomics, and quantification of bacterial genes to understand potential underlying mechanisms. Statistical analyses were done by generalized linear mixed-effects models. Thirty-two obstetric patients and 535 daily observations were included. The data revealed that probiotic supplementation significantly reduced the severity of nausea, vomiting, constipation, and improved life quality. Moreover, a low copy number of fecal bsh (bile salt hydrolase), which generates free bile acids, was associated with high vomiting scores and probiotic intake increased fecal bsh. In exploratory analysis without adjusting for multiplicity, a low fecal α-tocopherol, as well as a high abundance of Akkemansia muciniphila, was associated with high vomiting scores and times, respectively. The potential implications of these biomarkers in pregnancy and GI function are discussed. Probiotics likely produce free bile acids to facilitate intestinal mobility and metabolism.

Introduction: It is assumed that up to 50% of patients with functional bowel disorders with diarrhoea may suffer from bile acid (BA) malabsorption, which is considered as an underrecognized cause of chronic diarrhoea. Aim: To evaluate the indicators of BA metabolism in patients with irritable bowel syndrome (IBS). Material and methods: The study population included 28 healthy adults (control group), 108 patients with IBS with diarrhoea (IBS-D) and 37 with constipation (IBS-C), aged 18-44 years. All participants were assessed by symptoms questionnaires: VSI and FBDSI. High-performance liquid chromatography - mass spectrometry (HPLC-MS) was used to measure serum and faecal BA (sBA and fBA). Ultra-performance liquid chromatography - mass spectrometry (UPLC-MS) was used to evaluate the relative activity (RA) of gut bacterial bile salt hydrolase (BSH). Results: Primary sBA in absolute and percentages, total fBA, and primary fBA in absolute and percentages were higher, and secondary sBA and fBA in percentages were lower in the IBS-D group compared to the control and IBS-C groups (p < 0.01). The RA of gut bacterial BSH was lower in IBS-D compared to the control and IBS-C groups (p < 0.01). RA of gut bacterial BSH, secondary sBA and fBA correlated negatively with abdominal pain, bloating, stool frequency, Bristol scale, VSI, and FBDSI (p < 0.05 in all). Total fBA, primary sBA, and fBA correlated positively with the same clinical parameters (p < 0.05 in all). Conclusions: IBS-D patients had altered parameters of BA metabolism that were associated with the severity of clinical symptoms, disease severity, visceral sensitivity, and stool appearance and frequency. [ABSTRACT FROM AUTHOR]

Bile salt hydrolases (BSHs) are enzymes that are essential for the enterohepatic metabolism of bile acids (BAs). BSHs catalyze the production of unconjugated BAs and regulate the homeostasis of BA pool. This study identified Lactobacillus as a crucial BSH-encoding genus, and 16 main species were obtained using metagenomic data from publicly available human gut microbiome databases. Then, the 16 species of lactobacilli were classified into four typical categories by BSH phylotypes, including five species encoding BSH-T0, six species encoding BSH-T2, four species encoding BSH-T3, and Ligilactobacillus salivarius encoding both BSH-T0 and BSH-T3. The lactobacilli with the highest in vitro deconjugation activities against seven conjugated BAs were the BSH-T3-encoding strains. Furthermore, in vivo studies in mice administered four representative lactobacilli strains encoding different BSH phylotypes showed that treatment with BSH-T3-encoding Limosilactobacillus reuteri altered the structure of the gut microbiome and metabolome and significantly increased the levels of unconjugated BAs and total BA excretion. Our findings facilitated the taxonomic identification of crucial BSH-encoding lactobacilli in human gut microbiota and shed light on their contributions toward modulation of the enterohepatic circulation of BAs, which will contribute to future therapeutic applications of BSH-encoding probiotics to improve human health. [ABSTRACT FROM AUTHOR]

Bile salt hydrolase (BSH) is an intracellular enzyme which is produced by intestinal flora during the period of growth and reproduction. This enzyme has been suggested to be involved in the host's bile acid balance, lipid metabolism and metabolic responses. Therefore, BSH has always been a research hotspot. Detailed knowledge of BSH structure and substrate preferences is a solid foundation for the development of BSH related products. This review explains the source and distribution of BSH, test method for BSH activity. It also introduces enzymatic properties and genetic organization. Finally, the potential applications of BSH research are briefly discussed. This review would provide theoretical basis for the in-depth research of BSH, developments of related functional foods, and other industry applications.

BackgroundThe gut microbiota is closely linked to cholesterol metabolism-related diseases such as obesity and cardiovascular diseases. However, whether gut microbiota plays a causal role in cholelithiasis remains unclear.AimsThis study explored the causal relationship between gut microbiota and cholelithiasis. We hypothesize that the gut microbiota influences cholelithiasis development.MethodsA two-sample Mendelian randomization method was combined with STRING analysis to test this hypothesis. Summary data on gut microbiota and cholelithiasis were obtained from the MiBioGen (n=13,266) and FinnGen R8 consortia (n=334,367), respectively.ResultsClostridium senegalense, Coprococcus3, and Lentisphaerae increased the risk of cholelithiasis and expressed more bile salt hydrolases. In contrast, Holdemania, Lachnospiraceae UCG010, and Ruminococcaceae NK4A214 weakly expressed bile salt hydrolases and were implied to have a protective effect against cholelithiasis by Mendelian randomization analysis.ConclusionGut microbiota causally influences cholelithiasis and may be related to bile salt hydrolases. This work improves our understanding of cholelithiasis causality to facilitate the development of treatment strategies.

Hypercholesterolemia is a significant risk factor for cardiovascular disease and metabolic disorders. Probiotics are the essential constituents of the gastrointestinal microbiota that provide health-promoting effects. Cholesterol-lowering activity is a specific property of probiotics, improving the cholesterol metabolism without adverse effects. Thus, the purpose of this study was to investigate the hypocholesterolemic effect of single and mixed cholesterol-lowering probiotic strains (including Limosilactobacillus reuteri TF-7, Enterococcus faecium TF-18, and Bifidobacterium animalis TA-1) in high-cholesterol diet (HCD)-induced hypercholesterolemic rats. The results showed that the administration of single probiotics contributed to a reduction in the body weight gain, visceral organ indexes, hyperlipidemia, and hepatic steatosis and also an improvement in the gastrointestinal microbiota. Besides the effect of single cholesterol-lowering probiotics, three probiotics strains could also synergize their hypocholesterolemic effect when administered simultaneously. These findings indicate that three cholesterol-lowering probiotic strains are suitable for development as probiotic supplements to reduce the risk of diseases caused by cholesterol and exert health benefits with synergistic effect when administered simultaneously. [ABSTRACT FROM AUTHOR]

Background: The relationships among intestinal dysbiosis, bile acid (BA) metabolism disorders, and ulcerative colitis pathogenesis are now recognized. However, how specific strains regulate BA metabolism to alleviate colitis is still unclear. This study investigated the effects of Bacteroides dorei on the development of acute colitis and elucidated the underlying mechanisms. Methods: The safety of BDX-01 was evaluated in vitro and in vivo. 2.5% dextran sulfate sodium (DSS) induced colitis in C57BL/6 mice, Caco-2, and J774A.1 cells were used to evaluate the anti-inflammatory effect of BDX-01. qPCR and Western blotting were used to detect the expression of inflammatory pathways. Microbiota composition was analyzed by 16S rRNA gene sequencing. Enzyme activity analysis and targeted metabolomics were used to analyze fecal bile salt hydrolase (BSH) and BA levels. Antibiotic-induced pseudo-germ-free mice were used to investigate the role of gut microbiota in the alleviation of colitis by BDX-01. Results: We confirmed the safety of novel strain Bacteroides dorei BDX-01 in vitro and in vivo. Oral BDX-01 administration significantly ameliorated the symptoms and pathological damage of DSS-induced acute colitis. Moreoever, 16S rRNA sequencing and enzyme activity analysis showed that BDX-01 treatment increased intestinal BSH activity and the abundance of bacteria harboring this enzyme. Targeted metabolomics revealed that BDX-01 significantly increased intestinal BA excretion and deconjugation. Certain BAs act as FXR agonists. The ß-muricholic acid (ßMCA): taurine ß-muricholic acid (T-ßMCA) and cholic acid (CA): taurocholic acid (TCA) ratios and the deoxycholic acid (DCA) level decreased markedly in the colitis models but increased substantially in BDX-01-treated mice. The colonic farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) were upregulated in mice treated with BDX-01. BDX-01 downregulated the expression of colonic proinflammatory cytokines pyrin domain-containing 3 (NLRP3), ASC, cleaved caspase-1, and IL-1ß. Antibiotic treatment didn't abolish the protective effect of BDX-01 on colitis. In vitro studies showed TßMCA abolished the effects of BDX-01 on FXR activation and inhibition of the NLRP3 inflammasome activation. Conclusion: BDX-01 improved DSS-induced acute colitis by regulating intestinal BSH activity and the FXR-NLRP3 signaling pathway. Our findings indicate that BDX- 01 is a promising probiotic to improve the management of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background. One of the mechanisms of the of irritable bowel syndrome with diarrhea (IBS-D) is bile acid malabsorption (BAM). In addition to the use of bile acid sequestrants, probiotic bacteria synthesizing bile salt hydrolase (BSH) are promising in the treatment of probable BAM. The purpose of the study was to compare the effectiveness of combined treatment (a probiotic based on strains of Lactobacillus, Streptococcus, Bifidobacterium, Saccharomyces boulardii and cholestyramine) with cholestyramine monotherapy in the treatment of IBS-D. Materials and methods. A 12-week randomized study included 108 patients with IBS-D divided into a control group (n = 51) receiving only cholestyramine and an experimental group (n = 57) receiving a combination of cholestyramine and the study probiotic. At baseline, the relative activity of BSH of the study probiotic capsules was determined. During the stages of the study, patients were examined using clinical scales. Results. The relative activity of BSH of the capsules with the studied probiotic was (2.07 ± 0.06) U/ml compared to (1.00 ± 0.04) U/ml of capsules with L.plantarum and (0.03 ± 0.01) U/ml — with L.plantarum without BSH genes. In the experimental group, the severity of bloating and visceral sensitivity index were lower after 8 and 12 weeks, and the value of the stool type according to the Bristol scale and its daily frequency — after 12 weeks compared to the control group, p < 0.05. According to the scale of IBS-adequate relief, the percentage of achieving a clinical effect was higher in the experimental group compared to the controls after 12 weeks, odds ratio was 1.31 (95% confidence interval 1.03–1.68), p = 0.038. Conclusions. Additional prescription of a probiotic with BSH synthesizing bacterial strains is more effective in improving clinical manifestations of IBS-D and achieving a therapeutic effect compared to cholestyramine monotherapy. [ABSTRACT FROM AUTHOR]

Probiotics are known to possess strain- and species-specific functional properties, of which hypocholesteremia is of major interest. Bile salt hydrolase (BSH) activity is one of the key mechanisms involved in the hypocholesterolemic effect. The study was designed to genetically characterize probiotics obtained from human milk on the basis of simple sequence repeat (SSR), isolate potent hypocholesterolemic strains, and detect BSH activity, deconjugation of bile salts, and bsh polymorphism. This study, for the first time, linked genetic diversity with cholesterol reduction potential and proved the presence of conserved bsh of Levilactobacillus brevis in genetically diverse species. The strains displayed 2.78%–42.23% cholesterol reduction, which was not influenced by prebiotics. In this study, data obtained from SSR markers indicated 93.3% diversity, and based on cluster analysis, they were distributed into XI clades; out of five potent cholesterol-reducing strains, three belonged to clade I. The strains could deconjugate both sodium glycocholate and sodium taurocholate, but we preferred using sodium glycocholate. The variation in cholesterol reduction potential and BSH activity pointed toward the presence of more than one bsh in the strains. Weissella confusa MW051433 displayed highest cholesterol reduction (42.23%) and specific BSH activity (2.64 U ml −1). Search for other bsh and in vivo assessments of cholesterol reduction by W. confusa MW051433 have been proposed. [ABSTRACT FROM AUTHOR]

• Caloric restriction (CR) increases taurine levels in white adipose tissue (WAT). • The concentration of taurine reversely correlates with WAT weight. • The levels of taurine in WAT correlate with intestinal levels. • Gut microbiota and its bile salt hydrolase activity influence WAT taurine levels. • Restriction of dietary taurine impairs fat loss during CR. Previously, we demonstrated that caloric restriction (CR) stimulates the synthesis, conjugation, secretion, and deconjugation of taurine and bile acids in the intestine, as well as their reuptake. Given taurine's potent antiobesogenic properties, this study aimed to assess whether the CR-induced shift in taurine homeostasis contributes to adipose tissue loss. To verify that, male C57Bl/6 mice were subjected to 20% CR or ad libitum feeding, with variations in cage bedding and gut microbiota conditions. Additional groups received taurine supplementation or were fed a low-taurine diet (LTD). The results showed that in CR animals, taurine derived from the intestine was preferentially trafficked to epididymal white adipose tissue (eWAT) over other tested organs. Besides increased levels of taurine transporter TauT, gene expression of Cysteine dioxygenase (Cdo) involved in taurine synthesis was upregulated in CR eWAT. Taurine concentration in adipocytes was inversely correlated with fat pad weight of CR mice. Different types of cage bedding did not impact eWAT taurine levels; however, the lack of bedding and consumption of a diet high in soluble fiber did. Depleting gut microbiota with antibiotics or inhibiting bile salt hydrolase (BSH) activity reduced WAT taurine concentration in CR mice. Taurine supplementation increased taurine levels in WAT and brown adipose tissue (BAT), promoting fat loss in CR animals. LTD consumption blunted WAT loss in CR animals, with negligible impact on BAT. This study provides multiple insights into taurine's role in CR-triggered fat loss and describes a novel communication path between the liver, gut, microbiota, and WAT, with taurine acting as a messenger. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is a great threat to humans. Bile salt hydrolase (BSH)-producing lactic acid bacteria (LAB) may alleviate it, but current screening methods are inadequate. This study aimed to establish a more comprehensive in vitro method to screen BSH-producing LAB with greater potential for anti-hypercholesterolemia. Forty-one LAB were initially isolated from infant feces and 37 strains could produce BSH. Strains with BSH over 2 U/mg for sodium glycodeoxycholate and sodium taurodeoxycholate were used to analyse cholesterol degradation rate, hydrophobicity, self-aggregation, gastric fluid tolerance, and intestinal fluid tolerance. Based on the results of these indicators, Lactococcus lactis Y17, L. rhamnosus Q2, and L. fermentum Q11 with the top scores were considered anti-hypercholesterolemia candidates using a principal component analysis evaluation. Antioxidant and Caco-2 adhesion assays showed that these three strains exhibited excellent antioxidant ability and Caco-2 adhesion ability. Their total antioxidant capacity was above 0.99 μmol/L, while the Caco-2 adhesion rate was higher than 8.22%. Safety assessments, via antibiotic susceptibility and hemolysis tests, confirmed their safety. In the HepG2 cells assay, the total cholesterol content of the Y17, Q2, and Q11 groups was reduced by 0.525 mmol/L, 0.426 mmol/L, and 0.581 mmol/L, which verified the potential of the three LAB in anti-hypercholesterolemia. In addition, they could enhance cholesterol uptake and bile acid synthesis in HepG2 cells by upregulating the mRNA expression of bile acid synthase (CYP7A1 and CYP8B1) and cholesterol uptake receptors (NPC1L1 and LDLR). The results showed that the three LAB could be developed into anti-hypercholesterolemia foods with beneficial properties. [Display omitted] • Forty-one LAB were isolated from infant feces, and thirty-seven produced BSH. • Strains were evaluated for anti-hypercholesterolemia ability using PCA. • Three LAB candidates had excellent antioxidant capacity and Caco-2 cell adhesion. • The cholesterol-lowering activity of LAB candidates was assessed by HepG2 cells. • Three LAB candidates could upregulate the mRNA expression of CYP7A1 and CYP8B1. • Three LAB candidates could upregulate the mRNA expression of NPC1L1 and LDLR. [ABSTRACT FROM AUTHOR]

The bile acids (BAs) de-conjugation is catalyzed by bile salt hydrolase (BSH) enzyme, that is an intestinal bacterial product and a member of the cholylglycine hydrolase (CGH) family. De-conjugated BAs alter BA-mediated signaling pathways such as glucose metabolism, energy homeostasis and lipid absorption and this makes the BSH clinically important. However, BSHs from different sources have a variable substrate preference to eight different bile salts. Although BSH is a well-studied enzyme, its molecular investigations based on BSH substrate recognition are not very well known. In this study, the relationship between substrate specificity of BSH from Lactobacillus plantarum B14 (LpBSH) and its loop II, the aliphatic-hydrophobic V58 and aromatic-hydrophobic Y65 residues in this loop was mutated and analyzed. While PCR-based site-directed mutagenesis was used to substitute V58 and Y65 amino acids for N58, F58, M58, C65, F65 and L65 amino acids, respectively, the BLR (DE3) strain of E. coli was used to express mutant recombinant LpBSHs (mrLpBSHs). Site-directed mutagenesis of LpBSH showed reduced activity of mrLpBSHs against six different BAs. Our results indicated that the V58 and mostly Y65 residues in loop II might be critical for the structural site that is involved in substrate specificity and catalysis. These findings suggested that V58 and Y65 residues of LpBSH might participate in substrate specificity and BSH substrate specificity may be dependent upon the collate group, rather than amino acid moieties. However, more mutagenesis-based investigation on other CGH family members are needed in order to understand the structure and substrate specificity relations of BSHs. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Hydrobiology / Shuisheng Shengwu Xuebao is the property of Editorial Department of Journal of Hydrobiology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We performed whole-genome sequencing of Limosilactobacillus reuteri LU150, a human fecal isolate from the NORDBIOTIC collection. The genome consists of 2,039,406 bp with a GC content of 38.9%. The genetic content of LU150 suggests its probiotic potential., Competing Interests: The authors declare no conflict of interest.

Background & Aims: Liver kinase B1 (LKB1) is a master upstream protein kinase involved in nutrient sensing and glucose and lipid metabolism in many tissues; however, its metabolic role in intestinal epithelial cells (IEC) remains unclear. In this study, we investigated the regulatory role of LKB1 on bile acid (BA) homeostasis. Methods: We generated mice with IEC-specific deletion of LKB1 (LKB1ΔIEC) and analyzed the characteristics of IEC development and BA level. In vitro assays with small interfering RNA, liquid chromatography/mass spectrometry, metagenomics, and RNA-sequencing were used to elucidate the regulatory mechanisms underlying perturbed BA homeostasis. Results: LKB1 deletion resulted in abnormal differentiation of secretory cell lineages. Unexpectedly, BA pool size increased substantially in LKB1ΔIEC mice. A significant reduction of the farnesoid X receptor (FXR) target genes, including fibroblast growth factor 15/19 (FGF15/19), known to inhibit BA synthesis, was found in the small intestine (SI) ileum of LKB1ΔIEC mice. We observed that LKB1 depletion reduced FGF15/19 protein level in human IECs in vitro. Additionally, a lower abundance of bile salt hydrolase-producing bacteria and elevated levels of FXR antagonist (ie, T-βMCA) were observed in the SI of LKB1ΔIEC mice. Moreover, LKB1ΔIEC mice showed impaired conversion of retinol to retinoic acids in the SI ileum. Subsequently, vitamin A treatment failed to induce FGF15 production. Thus, LKB1ΔIEC mice fed with a high-fat diet showed improved glucose tolerance and increased energy expenditure. Conclusions: LKB1 in IECs manages BA homeostasis by controlling FGF15/19 production.

One of the most promising aspects of lactic acid bacteria (LAB) in foodstuffs with probiotic characteristics is cholesterol-lowering action. This study aimed to examine the bile salt hydrolase (BSH) positive strains; out of 50 LAB isolates, Lactiplantibacillus plantarum Lpb01 and Lpb02 were selected. Both Lpb01 and Lpb02 were more bile-tolerant strains, surviving in 1% bile for 3 h at up to 7.27 and 7.14 log CFU/mL, respectively. Lactiplantibacillus plantarum Lpb01 and Lpb02 deconjugated considerably more sodium glycocholate, releasing 5.50 ± 0.12 mM and 5.23 ± 0.41 mM cholic acid, respectively, compared with 4.32 ± 0.17 mM cholic acid released by ATCC 8014. In addition, Lpb. plantarum Lpb01 and Lpb02 deconjugated a considerably higher quantity of sodium glycocholate than ATCC 8014. Compared to ATCC 8014, Lactiplantibacillus plantarum Lpb01 and Lpb02 demonstrated a higher level of BSH activity. The tested strains Lactiplantibacillus plantarum Lpb01 and Lpb02 resulted in a 63–68% reduction in the cholesterol level in broth media, whereas the commercial strain Lpb. plantarum ATCC 8014 showed a 51% reduction. In the case of survivability during in vitro gastrointestinal (GI) digestion, they did not lyse in the presence of lysozyme, and they survived more than 96% of the time when exposed to pepsin and low acidity (pH 3) for 1.5 h. Finally, the LAB strains were resistant to bile salts and pancreatin, with an overall viability rate of 94.0–99.4% after exposure to small intestinal conditions. This suggests that the isolates can survive severe environment in the GI tract. As a result, these strains with demonstrated in vitro capabilities are promising candidates for novel probiotic-containing formulations and could be incorporated into functional dairy foods.

Metformin is widely used to surmount insulin resistance (IR) and type 2 diabetes. Accumulating evidence suggests that metformin may improve IR through regulating gut microbiota and bile acids. However, the underlying mechanisms remain unclear. Our metabolomic analysis showed that metformin significantly increased the accumulation of tauroursodeoxycholic acid (TUDCA) in intestine and liver from high-fat diet (HFD)-induced IR mice. TUDCA also alleviated IR, and reduced oxidative stress and intestinal inflammation in ob/ob mice. TUDCA blocked KEAP1 to bind with Nrf2, resulting in Nrf2 translocation into nuclear and initiating the transcription of antioxidant genes, which eventually reduced intracellular ROS accumulation and improved insulin signaling. Analysis of gut microbiota further revealed that metformin reduced the relative abundance of Bifidobacterium, which produces bile salt hydrolase (BSH). The reduction in BSH was probably crucial for the accumulation of TUDCA. Metformin also increased the proportion of Akkermanisia muciniphlia in gut microbiota of ob/ob mice via TUDCA. These beneficial effects of metformin in remodeling gut microbiota, reducing oxidative stress and improving insulin sensitivity were partly due to the accumulation of TUDCA, suggesting that TUDCA may be a potential therapy for metabolic syndrome.

Hypercholesterolemia prevalence is increasing in most countries and it increases the risk of microvascular and cardiovascular diseases. Currently available treatments include the use of statins, fibrates, and bile acid sequesters. These treatments carry a risk of severe side effects on the host. Probiotics are well documented for their cholesterol-lowering abilities. The present study has demonstrated the screening of probiotic bacteria from buttermilk samples, their ability to deconjugate bile salts, and cholesterol-lowering ability in the media. Bile salt hydrolysis by the isolates was evaluated by direct plate assay, thin layer chromatography, and cholic acid estimation. The highest amount of cholesterol was removed in the presence of 0.3% bile. Co-precipitation of cholesterol along with cholic acid was also observed. Three isolates considered potent based on their performance through all the tests were identified by 16S- rRNA gene sequencing as PGB01- Lacticaseibacillus paracasei, PGB02- Lactiplantibacillus plantarum, and PGB05- Lacticaseibacillus paracasei subsp. tolerans. [ABSTRACT FROM AUTHOR]

Dyslipidemia, specifically abnormal levels of low-density lipoprotein cholesterol (LDL-C), is an important risk factor of cardiovascular disease. Evidence showing the promising abilities of probiotics to lower total cholesterol or LDL-C has, however, not yet convinced experts to recommend probiotic bacteria as treatment for blood lipid management. Therefore, there are opportunities for the development of new efficient cholesterol-lowering probiotics. Bile salt hydrolase (BSH) and feruloyl esterase (FAE) are bacterial enzymes proposed to explain the cholesterol-lowering capacity of some bacteria and have both been shown to be responsible for lipid reduction in vivo. Here, in order to select for cholesterol-lowering bacteria, 70 strains related to Lactobacillaceae were screened for BSH and FAE activities. Based on this two-way screening approach, two bacteria were selected and assessed for their capacity to assimilate cholesterol in vitro, another suggested mechanism. Lactobacillus acidophilus CL1285 showed BSH and FAE activity as well as capacity to assimilate cholesterol in vitro. Lactiplantibacillus plantarum CHOL-200 exhibited BSH activity and ability to assimilate cholesterol. These properties observed in vitro make both strains good probiotic candidates for the management of dyslipidemia. Further investigation is needed to assess their ability to reduce blood cholesterol in human trial. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammation of gastrointestinal tract, with steadily increased incidence and prevalence worldwide. Although the precise pathogenesis remains unclear, gut microbiota, bile acids (BAs), and aberrant immune response play essential roles in the development of IBD. Lately, gut dysbiosis including certain decreased beneficial bacteria and increased pathogens and aberrant BAsmetabolism have been reported in IBD. The bacteria inhabited in human gut have critical functions in BA biotransformation. Patients with active IBD have elevated primary and conjugated BAs and decreased secondary BAs, accompanied by the impaired transformation activities (mainly deconjugation and 7α-dehydroxylation) of gutmicrobiota. Probiotics have exhibited certain positive effects by different mechanisms in the therapy of IBD. This review discussed the effectiveness of probiotics in certain clinical and animal model studies that might involve in gut microbiota-BAs axis. More importantly, the possible mechanisms of probiotics on regulating gutmicrobiota-BAs axis in IBD were elucidated, which we focused on the elevated gut bacteria containing bile salt hydrolase or BA-inducible enzymes at genus/species level that might participate in the BA biotransformation. Furthermore, beneficial effects exerted by activation of BAactivated receptors on intestinal immunity were also summarized, which might partially explain the protect effects and mechanisms of probiotics on IBD. Therefore, this review will provide new insights into a better understanding of probiotics in the therapy targeting gut microbiota-BAs axis of IBD. [ABSTRACT FROM AUTHOR]

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hypercholesterolemia is one of the major risk factors related to global health problems. Probiotics with cholesterollowering activity can improve cholesterol metabolism without any adverse effects. In this study, seventeen lactic acid bacteria (LAB) isolated from traditional Thai foods exhibited the ability to produce bile salt hydrolase (BSH) and assimilate cholesterol. From these isolates, Lactobacillus reuteri TF-7, Enterococcus faecium TF-18, and Bifidobacterium animalis TA-1 were selected for cholesterol-lowering LAB candidates due to their robust cholesterol reduction activity with different genera. Furthermore, these strains had proven to be safe and expressed different characteristics. L. reuteri TF-7 could produce gamma-aminobutyric acid (GABA), whereas B. animalis TA-1 was the most potent antioxidant strain. Moreover, all three LAB strains could tolerate under the acid and bile salt conditions, and adhered to the intestinal epithelial cells. According to these findings, three LAB strains are potential cholesterol-lowering probiotics, which can be applied as probiotic supplements.

[Display omitted] • Bacterial bile salt enzyme is able to hydrolase bile acids into free bile acids. • Bile salt hydrolase is widespread among gut microbes. • Most of lactobacilli encode bile salt hydrolase experimentally reduce cholesterol. • Lactobacilli probiotics-fortified functional food may prevent hypercholesterolemia. Bile Salt Hydrolase (BSH) is a bacterial enzyme (EC 3.5.1.24) that initiates the crucial deconjugation of bile acids (BAs), a process necessary for their transformation into secondary BAs by gut microbes. Recent advance has delved deeper into BAs, recognizing them as endocrine molecules capable of modulating lipid and sugar metabolism in the host. In this review, we elucidate how this wealth of research has broadened our understanding about the intricate mechanisms between BAs and the gut microbiota beyond BSH, underlying the hypocholesterolemic effects of probiotic lactobacilli. We highlight the expanded range of various species of lactobacilli with proven cholesterol-lowering activity both in vitro and in vivo associated with BSH activity. In addition, a summary of genomic and metagenomic studies investigating bsh genes in both gut microbiota and lactobacilli is provided, to be used as an additional tool for the selection of a potential lactobacilli probiotic. [ABSTRACT FROM AUTHOR]

Bile salt hydrolase (BSH) is a well-characterized probiotic enzyme associated with bile detoxification and colonization of lactic acid bacteria in the human gastrointestinal tract. Here, we isolated a putative BSH (LpBSH) from the probiotic bacterium Lactobacillus paragasseri JCM 5343T and demonstrated its bifunctional activity that allows it to degrade not only bile salts but also the antibiotic (penicillin). Although antibiotic resistance and bile detoxification have been separately recognized as different microbial functions, our findings suggest that bifunctional BSHs simultaneously confer ecological advantages to host gut bacteria to improve their survival in the mammalian intestine by attaining a high resistance to bile salts and β-lactams. Strain JCM 5343T showed resistance to both bile salts and β-lactam antibiotics, suggesting that LpBSH may be involved in this multi-resistance of the strain. We further verified that such bifunctional enzymes were broadly distributed among the phylogeny, suggesting that the bifunctionality may be conserved in other BSHs of gut bacteria. This study revealed the physiological role and phylogenetic diversity of bifunctional enzymes degrading bile salts and β-lactams in gut bacteria. Furthermore, our findings suggest that the hitherto-overlooked penicillin-degrading activity of penicillin acylase could be a potential new target for the probiotic function of gut bacteria. [ABSTRACT FROM AUTHOR]

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome.

Bile salt hydrolase (BSH) is a well-characterized probiotic enzyme associated with bile detoxification and colonization of lactic acid bacteria in the human gastrointestinal tract. Here, we isolated a putative BSH (LpBSH) from the probiotic bacterium Lactobacillus paragasseri JCM 5343T and demonstrated its bifunctional activity that allows it to degrade not only bile salts but also the antibiotic (penicillin). Although antibiotic resistance and bile detoxification have been separately recognized as different microbial functions, our findings suggest that bifunctional BSHs simultaneously confer ecological advantages to host gut bacteria to improve their survival in the mammalian intestine by attaining a high resistance to bile salts and β-lactams. Strain JCM 5343T showed resistance to both bile salts and β-lactam antibiotics, suggesting that LpBSH may be involved in this multi-resistance of the strain. We further verified that such bifunctional enzymes were broadly distributed among the phylogeny, suggesting that the bifunctionality may be conserved in other BSHs of gut bacteria. This study revealed the physiological role and phylogenetic diversity of bifunctional enzymes degrading bile salts and β-lactams in gut bacteria. Furthermore, our findings suggest that the hitherto-overlooked penicillin-degrading activity of penicillin acylase could be a potential new target for the probiotic function of gut bacteria.