Alterations in bile acid profile and pathways contribute to hepatic inflammation in cancer cachexia, a syndrome worsening the prognosis of cancer patients. As the gut microbiota impinges on host metabolism through bile acids, the current study aimed to explore the functional contribution of gut microbial dysbiosis to bile acid dysmetabolism and associated disorders in cancer cachexia. Using three mouse models of cancer cachexia (the C26, MC38 and HCT116 models), we evidenced a reduction in the hepatic levels of several secondary bile acids, mainly taurodeoxycholic (TDCA). This reduction in hepatic TDCA occurred before the appearance of cachexia. Longitudinal analysis of the gut microbiota pinpointed an ASV, identified as Xylanibacter rodentium, as a bacterium potentially involved in the reduced production of TDCA. Coherently, stable isotope-based experiments highlighted a robust decrease in the microbial 7α-dehydroxylation (7α-DH) activity with no changes in the bile salt hydrolase (BSH) activity in cachectic mice. This approach also highlighted a reduced microbial 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 12α-hydroxysteroid dehydrogenase (12α-HSDH) activities in these mice. The contribution of the lower production of TDCA to cancer cachexia was explored in vitro and in vivo. In vitro, TDCA prevented myotube atrophy, whereas in vivo hepatic whole transcriptome analysis revealed that TDCA administration to cachectic mice improved the unfolded protein response and cholesterol homeostasis pathways. Coherently, TDCA administration reversed hepatic cholesterol accumulation in these mice. Altogether, this work highlights the contribution of the gut microbiota to bile acid dysmetabolism and the therapeutic interest of the secondary bile acid TDCA for hepatic cholesterol homeostasis in the context of cancer cachexia. Such discovery may prove instrumental in the understanding of other metabolic diseases characterized by microbial dysbiosis. More broadly, our work demonstrates the interest and relevance of microbial activity measurements using stable isotopes, an approach currently underused in the microbiome field.

The gut microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in maintaining the delicate balance of human health. Emerging evidence suggests that microbiome disruptions can have far-reaching implications, ranging from the development of inflammatory diseases and cancer to metabolic disorders. Bacteriophages, or "phages", are viruses that specifically infect bacterial cells, and their interactions with the gut microbiome are receiving increased attention. Despite the recently revived interest in the gut phageome, it is still considered the "dark matter" of the gut, with more than 80% of viral genomes remaining uncharacterized. Today, research is focused on understanding the mechanisms by which phages influence the gut microbiota and their potential applications. Bacteriophages may regulate the relative abundance of bacterial communities, affect bacterial functions in various ways, and modulate mammalian host immunity. This review explores how phages can regulate bacterial functionality, particularly in gut commensals and pathogens, emphasizing their role in gut health and disease.

Recent studies have focused on the relationship between obesity and gut microbiota. This study aims to identify fecal components and gut bacterial species associated with different BMI categories. In this study, 538 participants aged ≥18 years were categorized into underweight, normal, and obese groups based on BMI (cutoffs: 18.5 and 25.0 kg/m²). We compared 30 fecal components among these groups and calculated correlation coefficients between each component and BMI. Participants were then divided into quartiles based on fecal component levels correlated with BMI, and the prevalence ratio (PR) of obesity was calculated, adjusted for confounding factors. We also analyzed the composition and diversity of gut microbiota and bacterial gene expression among the quartiles for each fecal component. Fecal glycocholic acid (GCA) showed a significant positive correlation with BMI. The PR for obesity in the highest quartile of fecal GCA was 3.30 (95% CI, 1.21-9.54), indicating a significantly higher risk of obesity compared to the lowest quartile. Gut microbiota analysis revealed significant differences in the abundance of Ruminococcaceae Incertae Sedis, Faecalibacterium, and Methanobrevibacter, with Methanobrevibacter being absent in the higher quartiles of fecal GCA. Additionally, gene expression for enzymes involved in the deconjugation of conjugated bile acids, including GCA, was downregulated in the highest quartile. Increased fecal GCA levels are positively correlated with obesity, alongside a depletion of archaea.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

In the current era, metabolic dysfunction-associated steatotic liver disease (MASLD) has gradually developed into a major type of chronic liver disease that is widespread globally. Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD. Currently, the gut microbiota has become one of the important entry points for the research of this disease. Therefore, the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD, including the changes and differences in the microbiota between the healthy liver and the diseased liver. Meanwhile, considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis (such as mild fibrosis and severe fibrosis) during the disease progression, we also conduct a comparison of the microbiota in these states and use them as markers of disease progression. It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota, and the impact of lipopolysaccharide from Gram-negative bacteria on the disease. In addition, the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics (including new-generation probiotics) will be explored, which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota. This will achieve important progress in preventing and combating this disease.

Nonalcoholic steatohepatitis (NASH) is a significant threat to human health. Our previous study revealed that salidroside attenuated NASH and regulated the gut microbiota. However, whether the therapeutic effect of salidroside depends on gut microbiota remains to be determined. Therefore, we conducted further experiments to elucidate the essential functions of gut microbiota-associated metabolic pathways in the anti-NASH effects of salidroside. Our results showed that salidroside effectively alleviated lipid accumulation and inflammatory injury in NASH mice. 16S rRNA sequencing revealed that salidroside increased the abundance of Bacteroides. Mice receiving fecal microbiota transplantation (FMT) from salidroside-treated also presented less hepatic steatosis and higher abundance of Bacteroides. Antibiotics eliminated the effects of salidroside on hepatic steatosis and the gut microbiota. Mechanistically, salidroside and FMT from salidroside-treated altered the bile acid (BA) profile by decreasing the levels of conjugated BAs and tauro-α/β-muricholic acid and activated downstream farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Furthermore, we found that inhibitors of bile salt hydrolase (BSH) and FXR/TGR5 abolished the effects of salidroside and reduced downstream carnitine palmitoyltransferase 1α and lipoprotein lipase expression. These data demonstrate that salidroside attenuated NASH via gut microbiota-BA-FXR/TGR5 signaling pathway and reveal the underlying mechanism of salidroside on NASH.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota's role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis and development of tumor. The adaptive immunity needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes in many cancers. In recent years, with increasing attention on the TLS in tumor microenvironment, TLSs have emerged as a novel target for anti-tumor therapy. Excitingly, studies have shown the contribution of TLSs to the adaptive immune responses. However, it is unclear how TLSs to form and how to more effectively defense against tumor through TLS formation. Recent studies have shown that the inflammation plays a critical role in TLS formation. Interestingly, studies have also found that gut microbiota can regulate the occurrence and development of inflammation. Therefore, we here summarize the potential effects of gut microbiota- mediated inflammation or immunosuppression on the TLS formation in tumor environments. Meanwhile, this review also explores how to manipulate mature TLS formation through regulating gut microbiota/metabolites or gut microbiota associated signal pathways for anti-tumor immunity, which potentially lead to a next-generation cancer immunotherapy.

Chicory (Cichorium intybus L.) is a commonly used vegetable in Europe and is also regarded as a plant for both medicinal and edible uses in China. Chicory exhibits a substantial abundance of sesquiterpene lactone compounds within its composition. The prevalence of metabolic syndrome (MetS) is increasing and has become a global public health issue threatening the well-being of the general population. Recent studies have identified plant secondary metabolites as potential substances for treating MetS. Sesquiterpene lactones, a type of secondary metabolite with diverse biological activities, have been reported to exhibit anti-inflammatory effects, reduce lipid accumulation, and normalize blood glucose levels. However, the therapeutic effects of chicory sesquiterpene lactones on MetS remain to be explored, and little is known about sesquiterpene lactones' effects on intestinal flora and bile acids (BAs). Therefore, the effects of total sesquiterpene lactones (TSLs) from chicory on metabolic disorders, intestinal flora, and BAs were investigated in this study. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, followed by administration of TSLs, total chicory extract (TCE), and pioglitazone (Pio) for another 8 weeks. TSL, TCE, and Pio interventions reduced body weight gain, hepatic lipid accumulation, and lipogenesis in HFD-fed mice and attenuated plasma biochemical parameters. Among them, TSLs exhibited more significant effects, prompting further analysis of their impact on intestinal flora and bile acid metabolism. TSL intervention influenced the composition and structure of intestinal flora and BAs. TSL intervention impacted the composition and structure of the intestinal flora, characterized by a decrease in the abundances of Allobaculum, unidentified_Coriobacteriaceae, and Odoribacter, while the abundances of Prevotella, unidentified_Erysipelotrichaceae and Akkermansia were increased. Additionally, the levels of BAs TCDCA, GDCA, UDCA, 12-ketoLCA, 7-ketoLCA, and 6,7-diketoLCA were reduced. The research results indicated that TSLs from chicory may serve as potential agents for regulating metabolic abnormalities associated with MetS, as their effects can influence intestinal flora and BAs. The conclusions of this study are expected to open new research trajectories in the field of food science and nutrition, providing a solid scientific basis and innovative intervention approaches for the development of strategies targeting MetS prevention and management.

The dynamic balance between pro- and anti-inflammatory networks decreases as individuals age, and intestinal dysbiosis can initiate and maintain low-grade systemic inflammation. Interactions between the microbiota and humans occur from the beginning of life and, in general, the diversity of microbiota decreases with aging. The microbiome produces different metabolites with systemic effects, including immune system regulation. This understanding will be useful in controlling inflammation and preventing metabolic changes. Therefore, this review aims to identify the main metabolites synthesized by the intestinal microbiota to be used as biomarkers associated with longevity. This is a narrative review using scientific articles published in the last 10 years in the following databases: PubMed, Scielo, and Lilacs, using the Boolean operators "and" or "or." For this review, we identified 5 articles. The main metabolites described in the literature to date are organic acids, bile acids (BAs), short-chain fatty acids, branched-chain amino acids, trimethylamine N-oxide (TMAO), and derivatives of tryptophan and indole. Among these, the only ones not yet well characterized in studies on longevity were BAs and TMAO. Glutamate and p-cresol were also highlighted in the literature, with a negative association with longevity. The others showed an association, mostly positive, and can be used as potential biomarkers correlated with healthy aging and, if better studied, as targets for intervention to promote health and well-being.

Liver metastasis is the leading cause of colorectal cancer (CRC)‑related mortality. Microbiota dysbiosis serves a role in the pathogenesis of colorectal liver metastases. Bile acids (BAs), cholesterol metabolites synthesized by intestinal bacteria, contribute to the metastatic cascade of CRC, encompassing colorectal invasion, migration, angiogenesis, anoikis resistance and the establishment of a hepatic pre‑metastatic niche. BAs impact inflammation and modulate the immune landscape within the tumor microenvironment by activating signaling pathways, which are used by tumor cells to facilitate metastasis. Given the widespread distribution of BA‑activated receptors in both tumor and immune cells, strategies aimed at restoring BA homeostasis and blocking metastasis‑associated signaling are of importance in cancer therapy. The present study summarizes the specific role of BAs in each step of colorectal liver metastasis, elucidating the association between BA and CRC progression to highlight the potential of BAs as predictive biomarkers for colorectal liver metastasis and their therapeutic potential in developing novel treatment strategies.

Sterols and bile acids are vital signaling molecules that play key roles in systemic functions, influencing the composition of the human gut microbiota, which maintains a symbiotic relationship with the host. Additionally, gut microbiota-encoded enzymes catalyze the conversion of sterols and bile acids into various metabolites, significantly enhancing their diversity and biological activities. In this review, we focus on the microbial transformations of sterols and bile acids in the gut, summarize the relevant bacteria, genes, and enzymes, and review the relationship between the sterols and bile acids metabolism of gut microbiota and human health. This review contributes to a deeper understanding of the crucial roles of sterols and bile acids metabolism by gut microbiota in human health, offering insights for further investigation into the interactions between gut microbiota and the host.

Systemic bile acid homeostasis plays an important role in human health. In this study, a physiologically based kinetic (PBK) model that includes microbial bile acid deconjugation and intestinal bile acid reuptake via the apical sodium-dependent bile acid transporter (ASBT) was applied to predict the systemic plasma bile acid concentrations in human upon oral treatment with the antibiotic tobramycin. Tobramycin was previously shown to inhibit intestinal deconjugation and reuptake of bile acids and to affect bile acid homeostasis upon oral exposure of rats. Kinetic parameters to define the effects of tobramycin on intestinal bile acid transport were determined in vitro using a Caco-2 cell layer Transwell model for studying the intestinal translocation of 4 model bile acids including glycochenodeoxycholic acid (GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and deoxycholic acid (DCA), the latter as a model for unconjugated bile acids (uBA). Kinetic constants for the effect of tobramycin on intestinal microbial deconjugation were taken from previous in vitro studies using anaerobic fecal incubations. The PBK model simulations predicted that exposure to tobramycin at the dose level also used in the previous 28 day rat study would reduce human plasma Cmax levels of GCA, GCDCA, GDCA, and DCA by 42.4%, 27.7%, 16.9%, and 75.8%. The reduction of conjugated bile acids is governed especially via an effect on ASBT-mediated intestinal uptake, and not via the effect of tobramycin on intestinal conjugation, likely because deconjugation happens to a large extent in the colon which has limited subsequent bile acid reuptake. The results reflect that oral exposure to xenobiotics that are not or poorly bioavailable can affect systemic bile acid homeostasis. Altogether, the PBK model appears to provide a 3R compliant tool to evaluate the effect of oral exposure to xenobiotics on host bile acid homeostasis via effects on intestinal bile acid deconjugation and reuptake.

The vagus nerve is proposed to enable communication between the gut microbiome and the brain, but activity-based evidence is lacking. We find that mice reared germ-free exhibit decreased vagal tone relative to colonized controls, which is reversed via microbiota restoration. Perfusing antibiotics into the small intestines of conventional mice, but not germ-free mice, acutely decreases vagal activity which is restored upon re-perfusion with intestinal filtrates from conventional, but not germ-free, mice. Microbiome-dependent short-chain fatty acids, bile acids, and 3-indoxyl sulfate indirectly stimulate vagal activity in a receptor-dependent manner. Serial perfusion of each metabolite class activates both shared and distinct neuronal subsets with varied response kinetics. Metabolite-induced and receptor-dependent increases in vagal activity correspond with the activation of brainstem neurons. Results from this study reveal that the gut microbiome regulates select metabolites in the intestinal lumen that differentially activate vagal afferent neurons, thereby enabling the microbial modulation of chemosensory signals for gut-brain communication.

The gut microbiota (GM), the set of microorganisms that colonizes our intestinal tract, can undergo many changes, some of which are age related. Several studies have shown the importance of maintaining a healthy GM for a good quality of life. In the elderly, maintaining a good GM may become a real defense against infection by pathogens, such as C. difficile. In addition to the GM, bile acids (BAs) have been shown to provide an additional defense mechanism against the proliferation of pathogenic bacteria and to regulate bacterial colonization of the gut. BAs are molecules produced in the host liver and secreted with the bile into the digestive tract, and they are necessary for the digestion of dietary lipids. In the gut, host-produced BAs are metabolized by commensal bacteria to secondary BAs. In general GM and host organisms interact in many ways. This review examines the relationship between GM, BAs, aging, and possible new approaches such as dietary interventions, administration of ursodesoxycholic acid/tauroursodesoxycholic acid (UDCA/TUDCA), and probiotics to enrich the microbial consortia of the GM in the elderly and achieve a eubiotic state necessary for maintaining good health. The presence of Firmicutes and Actinobacteria together with adequate levels of secondary BAs would provide protection and improve the frailty state in the elderly. In fact, an increase in secondary BAs has been observed in centenarians who have reached old age without serious health issues, which may justify their active role in achieving longevity.

Cholestatic liver injury is a hepatobiliary disorder primarily characterized by cholestasis, which significantly contributes to liver damage. The Yinzhihuang (YZH) oral preparation is an effective clinical treatment for cholestatic liver injury; however, the specific mechanism of action has not been clarified.

This study investigated YZH's pharmacological mechanisms associated with the microbe‒gut‒liver axis in cholestatic mice, offering new perspectives for the treatment of cholestasis.

YZH's protective effects were evaluated by evaluating serum liver injury indices and liver staining in an alpha-nephthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis mouse model. Colon hematoxylin‒eosin (H&E) and alcian blue staining and FITC‒dextran leakage assays were performed to assess intestinal barrier integrity. Fluorescence in situ hybridization was employed to analyze bacterial translocation. Additionally, 16S rRNA sequencing, fecal microbiota transplantation, and bile acid metabolomics analysis were conducted to examine the relationships among the microbiome, bile acid metabolism, and YZH formula.

We found that YZH administration alleviated symptoms of ANIT-induced hepatic pathological injury and fibrosis. In addition, YZH reduced the transfer of gut bacteria to liver tissue by maintaining an intact intestinal barrier. Notably, YZH influenced the intestinal microbiota composition, upregulated the abundance of bile acid metabolism-associated probiotic bacteria, including Clostridiales, Lachnospiraceae and Bifidobacterium pseudolongum; and downregulated the abundance of Escherichia-Shigella and Serratia, thereby promoting bile acid excretion.

YZH protects against cholestatic liver damage by promoting bile excretion and maintaining intestinal mucosal barrier integrity. Furthermore, YZH alleviates cholestasis in a gut microbiota-dependent manner, and upregulation of probiotics may be crucial for YZH's influence on bile acid metabolism.

Gut microbiota has been increasingly linked to metabolic health and diseases over the past few decades. Bile acids (BAs), the major components of bile, are bidirectionally linked to intestinal microbiota, also known as the gut microbiome-BA metabolic axis. Gut microbiota-derived bile salt hydrolase (BSH, EC 3.5.1.24), which catalyzes the "gateway" reaction in a wider pathway of bile acid modification, not only shapes the bile acid landscape, but also modulates the crosstalk between gut microbiota and host health. Therefore, microbial BSHs exhibit the potential to directly or indirectly influence microbial and host physiologies, and have been increasingly considered as promising targets for the modulation of gut microbiota to benefit animal and human health. However, their physiological functions in bacterial and host physiologies are still controversial and not clear. In this review, we mainly discuss the current evidence related to the physiological roles that BSHs played in gut microbiota and human health, and the possible underlying mechanisms. Meanwhile, we also present the potential applications of BSHs and BSH-producing probiotics in various fields. Finally, we describe several important questions that need to be addressed by further investigations. A detailed exploration of the physiological significance of BSHs will contribute to their future diagnostic and therapeutic applications in improving animal and human health.

The Western diet (WD) leads to hepatic lipid metabolism disorders. Previous studies have shown that the bile salt hydrolase 1 (bsh1) gene of Lactobacillus plantarum AR113 attenuates colitis under WD. In this study, we preliminarily explored how AR113 attenuates the hepatic inflammatory response in colitis mice on the WD. Our study suggests that the WD leads to abnormalities in hepatic lipid metabolism and dysbiosis of the gut microflora, and furthermore, there may be a correlation between abnormalities in lipid metabolism and hepatic inflammatory responses. AR113 significantly regulated lipid and bile acid metabolism in the liver of mice treated by WD and Dextran sulfate sodium (DSS), affected the structure of the mouse intestinal flora, and inhibited the expression of Sterol regulatory element-binding protein 1C (SREBP-1C) and P-NF-κB p65 at the protein level, thereby attenuating the hepatic injury phenotype. However, the bsh1 knockout strain did not exhibit the above function.

Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development1, metabolism2-4, immune responses5-7 and cognitive function8. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear9,10. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA-MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA-MCY increased BA production in an FXR-dependent manner, and BA-MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA-MCYs acting as intestinal FXR antagonists. The levels of BA-MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA-MCY levels, indicating that BA-MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA-MCYs are also present in human serum. Together, our results indicate that BA-MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.

In recent years, more and more scientific community, food producers, and food industry show increased interest in functional foods containing probiotics, which is a big challenge. The consumption of probiotics in the context of a balanced diet through the consumption of functional foods or through the intake of pharmaceutical preparations has proven to contribute to the improvement of human health, even contributing to the prevention of diseases. In order for probiotics to be considered suitable for consumption, they must contain a minimum concentration of viable cells, namely, at least 107 colony forming units of beneficial microbes per gram. Ensuring the viability of bacterial cells until the moment of consumption is the overriding priority of functional probiotic food manufacturers. Probiotic bacteria are subject to stress conditions not only during food manufacturing but also during gastrointestinal passage, which limit or even compromise their functionality. This paper first examines all the stressful conditions faced by probiotic cells in their production stages and related to the conditions present in the bioreactor fermentation and drying processes as well as factors related to the food matrix and storage. The stress situations faced by probiotic microorganisms during the gastrointestinal transit especially during stomach and intestinal residence are also analyzed. In order to understand the adaptation mechanisms of probiotic bacteria to gastrointestinal stress, intrinsic and adaptive mechanisms identified in probiotic strains in response to acid stress and to bile and bile acid stress are analyzed. In addition, improvement strategies for multiple stress tolerance of lactic acid bacteria through directions dealing with stress, accumulation of metabolites, use of protectants, and regulation of technological parameters are examined. Finally, the definition of postbiotics, inanimate microorganisms and/or their components conferring health benefits, is also introduced. Postbiotics include cell lysates, enzymes, and cell wall fragments derived from probiotic bacteria and may represent an alternative to the use of probiotics, when they do not tolerate stressful conditions.

The evolving infant gut microbiome influences host immune development and later health outcomes. Early antibiotic exposure could impact microbiome development and contribute to poor outcomes. Here, we use a prospective longitudinal birth cohort of n = 323 healthy term African American children to determine the association between antibiotic exposure and the gut microbiome through shotgun metagenomics sequencing as well as bile acid profiles through liquid chromatography-mass spectrometry.

Stool samples were collected at ages 4, 12, and 24 months for antibiotic-exposed (n = 170) and unexposed (n = 153) participants. A short-term substudy (n = 39) collected stool samples at first exposure, and over 3 weeks following antibiotics initiation. Antibiotic exposure (predominantly amoxicillin) was associated with minimal microbiome differences, whereas all tested taxa were modified by breastfeeding. In the short-term substudy, we observed microbiome differences only in the first 2 weeks following antibiotics initiation, mainly a decrease in Bifidobacterium bifidum. The differences did not persist a month after antibiotic exposure. Four species were associated with infant age. Antibiotic exposure was not associated with an increase in antibiotic resistance gene abundance or with differences in microbiome-derived fecal bile acid composition.

Short-term and long-term gut microbiome perturbations by antibiotic exposure were detectable but substantially smaller than those associated with breastfeeding and infant age.

Competitive exclusion is conventionally believed to prevent the establishment of a secondary strain of the same bacterial species in the gut microbiome, raising concerns for the deployment of live bacterial therapeutics (LBTs), especially if the bacterial chassis is a strain native to the gut. In this study, we investigated factors influencing competition dynamics in the murine gut using isogenic native Escherichia coli strains. We found that competition outcomes are context-dependent, modulated by microbiome complexity, LBT transgene expression, intestinal inflammation, and host diet. Furthermore, we demonstrated that native LBTs can establish long-term engraftment in the gut alongside a parental strain, with transgene-associated fitness effects influencing competition. We identified various interventions, including strategic dosing and dietary modulation, that significantly enhanced LBT colonization levels by 2 to 3 orders of magnitude. These insights provide a framework for optimizing LBT engraftment and efficacy, supporting their potential translation for human therapeutic applications.

Microbial metabolism of bile acids (BAs) is crucial for maintaining homeostasis in vertebrate hosts and environments. Although certain organisms involved in bile acid metabolism have been identified, a global, comprehensive elucidation of the microbes, metabolic enzymes, and bile acid remains incomplete. To bridge this gap, we employed hidden Markov models to systematically search in a large-scale and high-quality search library comprising 28,813 RefSeq multi-kingdom microbial complete genomes, enabling us to construct a secondary bile acid production gene catalog. This catalog greatly expanded the distribution of secondary bile acid production genes across 11 phyla, encompassing bacteria, archaea, and fungi, and extended to 14 habitats spanning hosts and environmental contexts. Furthermore, we highlighted the associations between secondary bile acids (SBAs) and gastrointestinal and hepatic disorders, including inflammatory bowel disease (IBD), colorectal cancer (CRC), and nonalcoholic fatty liver disease (NAFLD), further elucidating disease-specific alterations in secondary bile acid production genes. Additionally, we proposed the pig as a particularly suitable animal model for investigating secondary bile acid production in humans, given its closely aligned secondary bile acid production gene composition. This gene catalog provides a comprehensive and reliable foundation for future studies on microbial bile acid metabolism, offering new insights into the microbial contributions to health and disease.

Bile acid metabolism is an important function in both host and environmental microorganisms. The existing functional annotations from single source pose limitations on cross-habitat analysis. Our construction of a systematic secondary bile acid production gene catalog encompassing numerous high-quality reference sequences propelled research on bile acid metabolism in the global microbiome, holding significance for the concept of One Health. We further highlighted the potential of the microbiota-secondary bile acid axis as a target for the treatment of hepatic and intestinal diseases, as well as the varying feasibility of using animal models for studying human bile acid metabolism. This gene catalog offers a solid groundwork for investigating microbial bile acid metabolism across different compartments, including humans, animals, plants, and environments, shedding light on the contributions of microorganisms to One Health.

Through biochemical transformation of host-derived bile acids (BAs), gut bacteria mediate host-microbe crosstalk and sit at the interface of nutrition, the microbiome, and disease. BAs play a crucial role in human health by facilitating the absorption of dietary lipophilic nutrients, interacting with hormone receptors to regulate host physiology, and shaping gut microbiota composition through antimicrobial activity. Bile acid deconjugation by bacterial bile salt hydrolase (BSH) has long been recognized as the first necessary BA modification required before further transformations can occur. Here, we show that BSH activity is common among human gut bacterial isolates spanning seven major phyla. We observed variation in both the extent and the specificity of deconjugation of BAs among the tested taxa. Unexpectedly, we discovered that certain strains were capable of directly dehydrogenating conjugated BAs via hydroxysteroid dehydrogenases (HSD) to produce conjugated secondary BAs. These results challenge the prevailing notion that deconjugation is a prerequisite for further BA modifications and lay a foundation for new hypotheses regarding how bacteria act individually or in concert to diversify the BA pool and influence host physiology.

Behavioral dysfunctions in dogs represent one of the main social concerns, since they can endanger animals and human-dog relationship. Together with the trigger stimulus (human, animal, place, scent, auditory stimuli, objects), dogs can experience stressful conditions, either in multiple settings or unique situations, more often turning into generalized fear. Such a dysfunctional behavior can be associated with genetic susceptibility, environmental factors, traumatic experiences, and medical conditions. The available therapy, based on behavior approaches, environmental management, and neurochemical manipulation, through nutrition, supplements, medicines, and pheromones, represent the mainstays of the treatments currently accessible. Growing evidence in humans and animals highlight the importance of the gut-brain axis in the modulation of the brain physiology and behavior as well. Here, taking advantage of the next generation sequencing approach, we sought to investigate the potential connection between gut microbiota and microbiome in dogs suffering from generalized fear (n = 8), when compared to healthy subjects (n = 8), who all lived in different families. Faecal microbiota evaluation showed a differential abundance of taxa related to Proteobacteria and Firmicutes Phyla, between case and control dogs. Moreover, serum metabolomics documented significant alterations of molecules associated to GABA and glutamate neurotransmission in the patients, as well as bile acids metabolism. Overall, our preliminary and integrated investigations highlighted an intriguing role for the microbiome-metabolome network, allowing to further unveil the potential pathophysiology of relational issues in companion animals and paving the way for more effective therapeutical approaches.

Bile salt hydrolase (BSH), a probiotic-related enzyme with cholesterol-assimilating and anti-hypercholesterolemic abilities, has been isolated from intestinal bacteria; however, BSH activity of bacteria in bile-salt-free (non-intestinal) environments is largely unknown. Here, we aimed to identify BSH from non-intestinal Enterococcus faecium and characterize its enzymatic function. We successfully isolated a plasmid-encoded bsh (efpBSH) from E. faecium, and the recombinant EfpBSH showed BSH activity that preferentially hydrolyzed taurine-conjugated bile salts, unlike the activity of known BSHs. EfpBSH functioned optimally at pH 4.0 and 50 °C. EfpBSH exhibited very low amino acid sequence similarity (48.46%) to EfBSH from E. faecalis T2 isolated from human urine, although 241 sequences with 100% identity to EfpBSH were found in both plasmids and chromosomes of E. faecium strains inhabiting intestinal and non-intestinal environments. Phylogenetically, EfpBSH was not affiliated with any known BSH phylogroup and was clearly distinguished from previously identified BSHs from intestinal lactic acid bacteria. Our genome database analysis demonstrated that horizontal gene transfer causes global efpBSH distribution among E. faecium strains in various environments (soil, water, and intestinal samples) and geographical regions (Asia, Africa, Europe, North America, South America, and Australia/Oceania). Overall, our findings are the first to indicate that BSH is not an intestine-specific enzyme and that hitherto-overlooked probiotic candidates with BSH activity can exist in diverse environments.

Fecal microbiota transplantation (FMT) has been described useful as an adjunct treatment for chronic enteropathy in dogs. Different protocols can be used to prepare and store FMT preparations, however, the effect of these methods on microbial viability is unknown. We aimed (1) to assess the viability of several core intestinal bacterial species by qPCR and (2) to assess Peptacetobacter (Clostridium) hiranonis viability through culture to further characterize bacterial viability in different protocols for FMT preparations.

Bacterial abundances were assessed in feces from six healthy dogs by qPCR after propidium monoazide (PMA-qPCR) treatment for selective quantitation of viable bacteria. Conservation methods tested included lyophilization (stored at 4°C and at -20°C) and freezing with glycerol-saline solution (12.5%) and without any cryoprotectant (stored at -20°C). Additionally, the abundance of P. hiranonis was quantified using bacterial culture.

Using PMA-qPCR, the viability of Faecalibacterium, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and P. hiranonis was reduced in lyophilized fecal samples kept at 4°C and -20°C up to 6 months (p < 0.05). In frozen feces without cryoprotectant, only Streptococcus and E. coli were not significantly reduced for up to 3 months (p > 0.05). Lastly, no differences were observed in the viability of those species in glycerol-preserved samples up to 6 months (p > 0.05). When using culture to evaluate the viability of P. hiranonis, we observed that P. hiranonis abundance was lower in lyophilized samples kept at 4°C than -20°C; and P. hiranonis abundance was higher in glycerol-preserved samples for up to 6 months than in samples preserved without glycerol for up to 3 months. Moreover, the highest abundance of P. hiranonis was observed in glycerol-preserved feces. After 3 months, P. hiranonis was undetectable by culture in 83% (5/6) of the frozen samples without glycerol.

While the lyophilization procedure initially reduced P. hiranonis abundance, P. hiranonis viability was stable thereafter for up to 6 months at -20°C. The higher bacterial viability detected in fecal samples preserved with glycerol confirms the use of this cryoprotectant as a reliable method to keep bacteria alive in the presence of fecal matrix for FMT purposes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by hepatic steatosis associated with metabolic abnormalities. Recent research has shed light on the intricate interplay among interleukin-1 receptor 1 (IL1R1), gut microbiota, and bile acids in the pathogenesis of MASLD. This review aims to provide a comprehensive overview of the current understanding of the role of IL1R1, gut microbiota, and bile acids in MASLD, exploring their interrelationships and potential mechanisms. We summarize the evidence supporting the involvement of IL1R1 in inflammation, discuss the influence of gut microbiota on bile acid metabolism and its influence on liver health, and elucidate the bidirectional interactions among IL1R1 signaling, gut microbiota composition, and bile acid homeostasis in MASLD. Furthermore, we highlight emerging therapeutic strategies targeting these interrelated pathways for the management of MASLD.

Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.

Intramuscular fat (IMF) is a key indicator of chicken meat quality and emerging studies have indicated that the gut microbiome plays a key role in animal fat deposition. However, the potential metabolic mechanism of gut microbiota affecting chicken IMF is still unclear. Fifty-one broiler chickens were collected to identify key cecal bacteria and serum metabolites related to chicken IMF and to explore possible metabolic mechanisms. The results showed that the IMF range of breast muscle of Guizhou local chicken was 1.65 to 4.59%. The complexity and stability of ecological network of cecal microbiota in low-IMF chickens were higher than those in high-IMF chickens. Cecal bacteria positively related to IMF were Alistipes, Synergistes and Subdoligranulum, and negatively related to IMF were Eubacterium_brachy_group, unclassified_f_Lachnospiraceae, unclassified_f_Coriobacteriaceae, GCA-900066575, Faecalicoccus, and so on. Bile acids, phosphatidylethanolamine (Pe) 32:1 and other metabolites were enriched in sera of high-IMF chickens versus low-IMF chickens while riboflavin was enriched in sera of low-IMF chickens. Correlation analysis indicated that specific bacteria including Alistipes promote deposition of IMF in chickens via bile acids while the Eubacterium_brachy group, and Coriobacteriaceae promoted formation of riboflavin, glufosinate, C10-dats (tentative), and cilastatin and were not conducive to the IMF deposition.

Since the gut microbiota plays a crucial role in host metabolism and homeostasis, its alterations induced by xenobiotics such as pesticides, could pose a risk to host health. The pyrethroid insecticides were frequently detected in surface water (up to 13 mg/L worldwide), sediments, and agricultural products; additionally, some previous studies indicated that pyrethroid insecticides could cause disruption of gut homeostasis. Hence herein, the normally used pyrethroid lambda-cyhalothrin (LCT) was selected and studied for its effects on the intestinal microbial community and its related bile acid metabolism using mice as the model species. Results showed that the total amount of bile acids in plasma and fecal samples from LCT treated mice markedly increased compared to controls, which could be mainly ascribed to the significantly raised proportions of taurine conjugated bile acids in plasma, and the increase in fecal secondary bile acids. In gut microbial profiles, a significantly increased richness of Prevotellacea and a depletion of Lachnospiraceae were found at the family level upon the treatment with lambda-cyhalothrin. In conclusion, results obtained on bacterial and bile acid profiles corroborate that the treatment of mice with LCT could affect gut microbial community with accompanying changes in bile acid homeostasis.

The global prevalence of atopic diseases, including food allergy, is increasing and correlates with shifts in the commensal microbiota triggered by modern lifestyle factors. Current research focuses on the immunological mechanisms and microbial cues that regulate mucosal immunity and prevent allergic responses to food. We review the identification and characterization of novel antigen-presenting cell subsets that may be critical for the establishment and maintenance of tolerance to both food and intestinal bacteria. Microbially derived products, particularly from the Lachnospiraceae family of Clostridia, regulate intestinal homeostasis through a variety of mechanisms. Here, we highlight recent work on Clostridial metabolites and products that mediate protection against allergic responses to food.

The human gut microbiome is a dynamic and intricate ecosystem, composed of trillions of microorganisms that play a pivotal role in maintaining overall health and well-being. However, the gut microbiome is constantly exposed to various environmental factors, including the bile produced by the liver, which can significantly impact its composition and function. Bile acids, secreted by the liver and stored in the gallbladder, modulate the gut microbiome, influencing its composition and function. This altered microbiome profile can, in turn, impact the tumor microenvironment (TME), promoting an immunosuppressive environment that favors tumor growth and metastasis. Furthermore, changes in the gut microbiome can also influence the production of bile acids and other metabolites that directly affect cancer cells and their behavior. Moreover, bile acids have been shown to shape the microbiome and increase antibiotic resistance, underscoring the need for targeted interventions. This review provides a comprehensive overview of the intricate relationships between bile, the gut microbiome, and the TME, highlighting the mechanisms by which this interplay drives cancer progression and resistance to therapy. Understanding these complex interactions is crucial for developing novel therapeutic strategies that target the gut-bile-TME axis and improve patient outcomes.

Obesity is a complex disease that increases the risk of other pathologies. Its prevention and long-term weight loss maintenance are problematic. Gut microbiome is considered a potential obesity modulator. The objective of the present study was to summarize recent findings regarding the relationships between obesity, gut microbiota, and diet (vegetable/animal proteins, high-fat diets, restriction of carbohydrates), with an emphasis on dietary fiber and resistant starch. The composition of the human gut microbiome and the methods of its quantification are described. Products of the gut microbiome metabolism, such as short-chain fatty acids and secondary bile acids, and their effects on the gut microbiota, intestinal barrier function and immune homeostasis are discussed in the context of obesity. The importance of dietary fiber and resistant starch is emphasized as far as effects of the host diet on the composition and function of the gut microbiome are concerned. The complex relationships between human gut microbiome and obesity are finally summarized.

The intestinal microbiota comprises approximately 1013-1014 species of bacteria and plays a crucial role in host metabolism by facilitating various chemical reactions. Secondary bile acids (BAs) are key metabolites produced by gut microbiota.Initially synthesized by the liver, BA undergoes structural modifications through the activity of various intestinal microbiota enzymes, including eukaryotic, bacterial, and archaeal enzymes. These modified BA then activate specific receptors that regulate multiple metabolic pathways in the host, such as lipid and glucose metabolism, energy balance, inflammatory response, and cell proliferation and death. Recent attention has been given to intestinal flora disorders in diabetic kidney disease (DKD), where activation of BA receptors has shown promise in alleviating diabetic kidney damage by modulating renal lipid metabolism and mitochondrial production. Imbalances in the intestinal flora can influence the progression of DKD through the regulation of bile acid and its receptor pathways. This review aims to propose a mechanism involving the gut-BA-diabetes and nephropathy axes with the goal of optimizing new strategies for treating DKD.

An imbalance between primary and secondary bile acids contributes to the development of metabolic dysfunction-associated steatohepatitis (MASH). The precise mechanisms underlying changes in the bile acid pool in MASH remain to be identified. As gut bacteria convert primary bile acids to secondary bile acids, we investigated the contribution of the gut microbiota and its metabolizing activities to bile acid alterations in MASH.

To disentangle the influence of MASH from environmental and dietary factors, high-fat diet fed foz/foz mice were compared with their high-fat diet fed wildtype littermates. We developed functional assays (stable isotope labeling and in vitro experiments) to extend the analyses beyond a mere study of gut microbiota composition (16S rRNA gene sequencing). Key findings were confirmed in C57BL/6J mice were fed a Western and high-fructose diet, as an independent mouse model of MASH.

Although mice with MASH exhibited lower levels of secondary 7α-dehydroxylated bile acids (3.5-fold lower, p = 0.0008), the gut microbial composition was similar in mice with and without MASH. Similar gut microbial bile salt hydrolase and 7α-dehydroxylating activities could not explain the low levels of secondary 7α-dehydroxylated bile acids. Furthermore, the 7α-dehydroxylating activity was unaffected by Clostridium scindens administration in mice with a non-standardized gut microbiota. By exploring alternative mechanisms, we identified an increased bile acid 7α-rehydroxylation mediated by liver CYP2A12 and CYP2A22 enzymes (4.0-fold higher, p <0.0001), that reduces secondary 7α-dehydroxylated bile acid levels in MASH.

This study reveals a gut microbiota-independent mechanism that alters the level of secondary bile acids and contributes to the development of MASH in mice.

Although changes in bile acid levels are implicated in the development of metabolic dysfunction-associated steatohepatitis (MASH), the precise mechanisms underpinning these alterations remain elusive. In this study, we investigated the mechanisms responsible for the changes in bile acid levels in mouse models of MASH. Our results support that neither the composition nor the metabolic activity of the gut microbiota can account for the alterations in the bile acid pool. Instead, we identified hepatic 7α-rehydroxylation of secondary bile acids as a gut microbiota-independent factor contributing to the reduced levels of secondary bile acids in mice with MASH. Further investigation is warranted to understand bile acid metabolism and its physiological implications in clinical MASH. Nonetheless, our findings hold promise for exploring novel therapeutic interventions for MASH.

The gut microbiota refers to the diverse bacterial community residing in the gastrointestinal tract. Recent data indicate a strong correlation between alterations in the gut microbiota composition and the onset of various diseases, notably cardiovascular disorders. Evidence suggests the gut-cardiovascular axis signaling molecules released by the gut microbiota play a pivotal role in regulation. This review systematically delineates the association between dysbiosis of the gut microbiota and prevalent cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction and heart failure. Furthermore, it provides an overview of the putative pathogenic mechanisms by which dysbiosis in the gut microbiota contributes to the progression of cardiovascular ailments. The potential modulation of gut microbiota as a preventive strategy against cardiovascular diseases through dietary interventions, antibiotic therapies and probiotic supplementation is also explored and discussed within the present study.

Polysaccharides can benefit the liver via modulation of the gut microbiota, but the exact mechanism is still unclear. This study demonstrated that the effect of Scytosiphon lomentaria fucoidan (SLF) on alcohol-induced liver injury can be closely related to the level of Parabacteroides distasonis (Pd) via in vivo and in vitro models. Further mice experiment showed that Pd alleviated liver injury and inflammation by suppressing the NF-κB/MAPK pathways and activating Nrf2 pathway. The underlying mechanism can be closely associated with modulation of the gut microbiota, particularly an increase in microbiota diversity and beneficial bacteria and a reduction in Proteobacteria. Targeted metabolomics indicated that Pd ameliorated alcohol-induced dysbiosis of microbiota metabolites profile, primarily affecting amino acid metabolism. Moreover, Pd reduced the level of total bile acids (BAs) and improved BAs profile, affecting the expression levels of BA-associated genes in the liver and ileum involved in BA synthesis, transport, and reabsorption. This study suggests that SLF can benefit alcohol-induced liver injury via P. distasonis-mediated regulation of the gut-liver axis.

Bile acids are increasingly appearing in the spotlight owing to their novel impacts on various host processes. Similarly, there is growing attention on members of the microbiota that are responsible for bile acid modifications. With recent advances in technology enabling the discovery and continued identification of microbially conjugated bile acids, the chemical complexity of the bile acid landscape in the body is increasing at a rapid pace. In this Review, we summarize our current understanding of how bile acids and the gut microbiota interact to modulate immune responses during homeostasis and disease, with a particular focus on the gut.

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), other than being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA gene sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentrations of BHB and nonesterified fatty acids (NEFA) but decreased concentrations of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine-conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHB). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period.