Microbiota and other detrimental metabolites in colorectal cancer.

Increasing scientific evidence demonstrates that gut microbiota plays an essential role in the onset and development of Colorectal cancer (CRC). However, the mechanisms by which these microorganisms contribute to cancer development are complex and far from completely clarified. Specifically, the impact of gut microbiota-derived metabolites on CRC is undeniable, exerting both protective and detrimental effects. This paper examines the effects and mechanisms by which important bacterial metabolites exert detrimental effects associated with increased risk of CRC. Metabolites considered include heterocyclic amines and polycyclic aromatic hydrocarbons, heme iron, secondary bile acids, ethanol, and aromatic amines. It is necessary to delve deeper into the mechanisms of action of these metabolites in CRC and identify the microbiota members involved in their production. Furthermore, since diet is the main factor capable of modifying the intestinal microbiota, conducting studies that include detailed descriptions of dietary interventions is crucial. All this knowledge is essential for developing precision nutrition strategies to optimise a protective intestinal microbiota against CRC.

UDCA ameliorates inflammation driven EMT by inducing TGR5 dependent SOCS1 expression in mouse macrophages.

Long-standing chronic inflammation of the digestive tract leads to Inflammatory Bowel Diseases (IBD), comprising Crohn's Disease (CD) and Ulcerative colitis (UC). The persistent prevalence of these conditions in the gut is a predisposing factor for Colitis-Associated Cancer (CAC), one of the most common sub-types of Colorectal Cancer (CRC), emphasizing the role of inflammation in tumorigenesis. Therefore, targeted intervention of chronic intestinal inflammation is a potential strategy for preclusion and treatment of inflammation-driven malignancies. The association between bile acids (BA) and gut immune homeostasis has been explored in the recent past. However, the exact downstream mechanism by which secondary BA successfully regulating intestinal inflammation and inflammation-dependent CAC is unclear. Our study demonstrated that Ursodeoxycholic acid (UDCA), a secondary bile acid of host gut microbial origin, finetunes the dialogue between activated macrophages and intestinal epithelial cells, modulating inflammation-driven epithelial-mesenchymal transition (EMT), a hallmark of cancer. UDCA treatment and dependency on the TGR5/GPBAR1 receptor significantly upregulated the Suppressor of Cytokine Signaling 1 (SOCS1) expression, contributing to the regulation of pro-inflammatory cytokines in activated macrophages. In this study, we also noticed heightened expression of SOCS1 in UDCA-mitigated CAC in the AOM-DSS mouse model with reduced inflammatory gene expression. Overall, our observations highlight the possible utility of UDCA for inflammation-driven intestinal cancer.

Unraveling the gut microbiota of Tibetan chickens: insights into highland adaptation and ecological advantages.

Tibetan animals have several unique advantages owing to the harsh ecological conditions under which they live. However, compared to Tibetan mammals, understanding of the advantages and underlying mechanisms of the representative high-latitude bird, the Tibetan chicken (Gallus gallus, TC), remains limited. The gut microbiota of animals has been conclusively shown to be closely related to both host health and host environmental adaptation. This study aimed to explore the relationships between the cecal microbiome and the advantages of TCs based on comparisons among three populations: native TCs residing on the plateau, domestic TCs living in the plain, and one native plain species. Metatranscriptomic sequencing revealed a significant enrichment of active Bacteroidetes but a loss of active Firmicutes in native TCs. Additionally, the upregulated expression of genes in the cecal microbiome of native TCs showed enriched pathways related to energy metabolism, glycan metabolism, and the immune response. Furthermore, the expression of genes involved in the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) was upregulated in the cecal microbiome of native TCs. Data from targeted metabolomics further confirmed elevated levels of certain SCFAs and SBAs in the cecum of native TCs. Based on the multi-omics association analysis, we proposed that the higher ratio of active Bacteroidetes/Firmicutes may be attributed to the efficient energy metabolism and stronger immunological activity of native TCs. Our findings provide a better understanding of the interactions between gut microbiota and highland adaptation, and novel insights into the mechanisms by which Tibetan chickens adapt to the plateau hypoxic environment. IMPORTANCE: The composition and function of the active cecal microbiome were significantly different between the plateau Tibetan chicken population and the plain chicken population. Higher expression genes related to energy metabolism and immune response were found in the cecal microbiome of the plateau Tibetan chicken population. The cecal microbiome in the plateau Tibetan chicken population exhibited higher biosynthesis of short-chain fatty and secondary bile acids, resulting in higher cecal content of these metabolites. The active Bacteroidetes/Firmicutes ratio in the cecal microbiome may contribute to the high-altitude adaptive advantage of the plateau Tibetan chicken population.

Gut microbial changes associated with obesity in youth with type 1 diabetes: a Pilot Study.

CONTEXT: Obesity is prevalent in type 1 diabetes (T1D) and is problematic with higher risk for diabetes complications. It is unknown to what extent gut microbiome changes are associated with obesity and T1D. OBJECTIVE: To describe the gut microbiome and microbial metabolite changes associated with obesity in T1D. We hypothesized significant gut microbial and metabolite differences in lean T1D youth (BMI: 5-<85%) vs. those with obesity (BMI: ≥95%). METHODS: We analyzed stool samples for gut microbial (using metagenomic shotgun sequencing) and short-chain fatty acid (SCFA) differences in lean (n=27) and obese (n=21) T1D youth in a pilot study. The mean±SD age was 15.3±2.2yrs, A1c 7.8±1.3%, diabetes duration 5.1±4.4yrs, 42.0% females, and 94.0% were White. RESULTS: Bacterial community composition showed between sample diversity differences (ß-diversity) by BMI group (p=0.013). There was a higher ratio of Prevotella to Bacteroides in the obese group (p=0.0058). There was a differential distribution of significantly abundant taxa in either the lean or obese groups, including increased relative abundance of Prevotella copri, among other taxa in the obese group. Functional profiling showed an upregulation of branched chain amino acid (BCAA) biosynthesis in the obese group and upregulation of BCAA degradation, tyrosine metabolism and secondary bile acid biosynthesis in the lean group. Stool SCFAs were higher in the obese versus the lean group (p<0.05 for all). CONCLUSIONS: Our findings identify a gut microbiome and microbial metabolite signature associated with obesity in T1D. These findings could help identify gut microbiome targeted therapies to manage obesity in T1D.

Gut Microbiota Metabolite Messengers in Brain Function and Pathology at a View of Cell Type-Based Receptor and Enzyme Reaction.

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

Cholecystohepatic shunt pathway reduces secondary bile acid accumulation to enhance natural killer T cell-mediated anti-hepatocellular carcinoma immunity.

BACKGROUND AND AIM: The impact of cholecystectomy, which blocks the cholecystohepatic shunt pathway (CHSP), on the prognosis of patients with hepatocellular carcinoma (HCC) is unclear. Hepatic secondary bile acids (BAs) inhibit natural killer T (NKT) cell-mediated immunity against HCC, and the regulation of homeostasis of hepatic secondary BAs is controlled by the CHSP. However, the influence of CHSP on NKT cell-mediated immunity against HCC remains unclear. METHODS: The clinical data of hospitalized patients undergoing HCC resection were collected. Meanwhile, an in situ HCC mouse model was established, and the CHSP was augmented using oleanolic acid (OA). RESULTS: After 1:1 propensity score matching, Cox regression analysis revealed that cholecystectomy was an independent risk factor for HCC recurrence after hepatectomy (P = 0.027, hazard ratio: 1.599, 95% confidence interval: 1.055-2.422). Experimentally, when OA enhanced CHSP, a significant decrease was observed in the accumulation of secondary BAs in the livers of mice. Additionally, a significant increase was observed in the levels of C-X-C ligand 16 and interferon γ in the serum and tumor tissues. Further, the percentage of C-X-C receptor 6 (+) NKT cells in the tumor tissues increased significantly, and the growth of liver tumors was inhibited. CONCLUSIONS: This clinical study revealed that cholecystectomy promoted the recurrence after radical hepatectomy in patients with HCC. Preserving the normal-functioning gallbladder as much as possible during surgery may be beneficial to the patient's prognosis. Further investigation into the mechanism revealed that CHSP enhanced NKT cell-mediated immunity against HCC by reducing the hepatic accumulation of secondary BAs.

Preservation of conjugated primary bile acids by oxygenation of the small intestinal microbiota in vitro.

Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and absorption of food. Primary bile acids delivered into the small intestine are conjugated to enhance functionality, in part, by increasing aqueous solubility and preventing passive diffusion of bile acids out of the gut lumen. Bile acid function can be disrupted by the gut microbiota via the deconjugation of primary bile acids by bile salt hydrolases (BSHs), leading to their conversion into secondary bile acids through the expression of bacterial bile acid-inducible genes, a process often observed in malabsorption due to small intestinal bacterial overgrowth. By modeling the small intestinal microbiota in vitro using human small intestinal ileostomy effluent as the inocula, we show here that the infusion of physiologically relevant levels of oxygen, normally found in the proximal small intestine, reduced deconjugation of primary bile acids, in part, through the expansion of bacterial taxa known to have a low abundance of BSHs. Further recapitulating the small intestinal bile acid composition of the small intestine, limited conversion of primary into secondary bile acids was observed. Remarkably, these effects were preserved among four separate communities, each inoculated with a different small intestinal microbiota, despite a high degree of taxonomic variability under both anoxic and aerobic conditions. In total, these results provide evidence for a previously unrecognized role that the oxygenated environment of the small intestine plays in the maintenance of normal digestive physiology. IMPORTANCE: Conjugated primary bile acids are produced by the liver and exist at high concentrations in the proximal small intestine, where they are critical for proper digestion. Deconjugation of these bile acids with subsequent transformation via dehydroxylation into secondary bile acids is regulated by the colonic gut microbiota and reduces their digestive function. Using an in vitro platform modeling the small intestinal microbiota, we analyzed the ability of this community to transform primary bile acids and studied the effect of physiological levels of oxygen normally found in the proximal small intestine (5%) on this metabolic process. We found that oxygenation of the small intestinal microbiota inhibited the deconjugation of primary bile acids in vitro. These findings suggest that luminal oxygen levels normally found in the small intestine may maintain the optimal role of bile acids in the digestive process by regulating bile acid conversion by the gut microbiota.

Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice.

Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.

Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome.

The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12-1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Postbiotics: emerging therapeutic approach in diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients that poses a serious risk as it can cause substantial visual impairment and even vision loss. Due to the prolonged onset of DR, lengthy treatment duration, and limited therapeutic effectiveness, it is extremely important to find a new strategy for the treatment of DR. Postbiotic is an emerging dietary supplement which consists of the inactivate microbiota and its metabolites. Numerous animal experiments have demonstrated that intervention with postbiotics reduces hyperglycemia, attenuates retinal peripapillary and endothelial cell damage, improves retinal microcirculatory dysfunction, and consequently delays the progression of DR. More strikingly, unlike conventional probiotics and prebiotics, postbiotics with small molecules can directly colonize the intestinal epithelial cells, and exert heat-resistant, acid-resistant, and durable for storage. Despite few clinical significance, oral administration with postbiotics might become the effective management for the prevention and treatment of DR. In this review, we summarized the basic conception, classification, molecular mechanisms, and the advances in the therapeutic implications of postbiotics in the pathogenesis of DR. Postbiotics present great potential as a viable adjunctive therapy for DR.

Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study.

BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D. CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

Collaborative Metabolism: Gut Microbes Play a Key Role in Canine and Feline Bile Acid Metabolism.

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.

Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma.

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.

Gut microbiota-derived 12-ketolithocholic acid suppresses the IL-17A secretion from colonic group 3 innate lymphoid cells to prevent the acute exacerbation of ulcerative colitis.

Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating the group 3 innate lymphoid cells (ILC3s), which are essential for intestinal health, remains unexplored during the development of disease severity. Here, our results showed that the microbiota structure of patients with severe UC (SUCs) differed from those with mild UC (MiUCs), moderate UC (MoUCs), and healthy controls (HCs). Microbes producing secondary bile acids (SBAs) and SBAs decreased with the aggravation of UC, and a strong positive correlation existed between them. Next, fecal microbiota transfer was used to reproduce the human-derived microbiota in mice and decipher the microbiota-mediated inflammatory modulation during an increase in disease severity. Mice receiving SUC-derived microbiota exhibited enhancive inflammation, a lowered percentage of ILC3s, and the down-regulated expressions of bile acid receptors, including vitamin D receptor (VDR) and pregnane X receptor (PXR), in the colon. Similar to clinical results, SBA-producing microbes, deoxycholic acids (DCA), and 12-ketolithocholic acids (12-KLCA) were diminished in the intestine of these recipients. Finally, we compared the therapeutic potential of DCA and 12-KLCA in preventing colitis and the regulatory mechanisms mediated by ILC3s. 12-KLCA but not DCA represented a strong anti-inflammatory effect associated with the higher expression of VDR and the lower secretion of IL-17A from colonic ILC3s. Collectively, these findings provide new signatures for monitoring the acute deterioration of UC by targeting gut microbiota and bile acid metabolism and demonstrate the therapeutic and preventive potential of a novel microbiota-derived metabolite, 12-KLCA.

Lactiplantibacillus plantarum GL001 alleviates jejunal oxidative damage induced by intestinal ischemia-reperfusion injury by influencing jejunal tissue metabolism through the improvement of jejunal microbial composition.

Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.

The microbial-derived bile acid lithocholate and its epimers inhibit Clostridioides difficile growth and pathogenicity while sparing members of the gut microbiota.

Clostridioides difficile is a Gram-positive, spore-forming anaerobe that causes clinical diseases ranging from diarrhea and pseudomembranous colitis to toxic megacolon and death. C. difficile infection (CDI) is associated with antibiotic usage, which disrupts the indigenous gut microbiota and causes the loss of microbial-derived secondary bile acids that normally provide protection against C. difficile colonization. Previous work has shown that the secondary bile acid lithocholate (LCA) and its epimer isolithocholate (iLCA) have potent inhibitory activity against clinically relevant C. difficile strains. To further characterize the mechanisms by which LCA and its epimers iLCA and isoallolithocholate (iaLCA) inhibit C. difficile, we tested their minimum inhibitory concentration against C. difficile R20291 and a commensal gut microbiota panel. We also performed a series of experiments to determine the mechanism of action by which LCA and its epimers inhibit C. difficile through bacterial killing and effects on toxin expression and activity. Additionally, we tested the cytotoxicity of these bile acids through Caco-2 cell apoptosis and viability assays to gauge their effects on the host. Here, we show that the epimers iLCA and iaLCA strongly inhibit C. difficile growth in vitro while sparing most commensal Gram-negative gut microbes. We also show that iLCA and iaLCA have bactericidal activity against C. difficile, and these epimers cause significant bacterial membrane damage at subinhibitory concentrations. Finally, we observe that iLCA and iaLCA decrease the expression of the large cytotoxin tcdA, while LCA significantly reduces toxin activity. Although iLCA and iaLCA are both epimers of LCA, they have distinct mechanisms for inhibiting C. difficile. LCA epimers, iLCA and iaLCA, represent promising compounds that target C. difficile with minimal effects on members of the gut microbiota that are important for colonization resistance. IMPORTANCE In the search for a novel therapeutic that targets Clostridioides difficile, bile acids have become a viable solution. Epimers of bile acids are particularly attractive as they may provide protection against C. difficile while leaving the indigenous gut microbiota largely unaltered. This study shows that LCA epimers isolithocholate (iLCA) and LCA epimers isoallolithocholate (iaLCA) specifically are potent inhibitors of C. difficile, affecting key virulence factors including growth, toxin expression, and activity. As we move toward the use of bile acids as therapeutics, further work will be required to determine how best to deliver these bile acids to a target site within the host intestinal tract.

Bile Acids and Short-Chain Fatty Acids Are Modulated after Onion and Apple Consumption in Obese Zucker Rats.

Gut microorganisms are involved in the development and severity of different cardiovascular diseases, and increasing evidence has indicated that dietary fibre and polyphenols can interact with the intestinal microbiota. The study objective was to investigate the effect of onion and apple intake on the major types of microbial-derived molecules, such as short-chain fatty acids (SCFAs) and bile acids (BAs). Obese Zucker rats were randomly assigned (n = eight rats/group) to a standard diet (OC), a standard diet/10% onion (OO), or a standard diet/10% apple (OA). Lean Zucker rats fed a standard diet served as a lean control (LC) group. Faecal samples were collected at baseline, and 8 weeks later, the composition of the microbial community was measured, and BA and SCFA levels were determined using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS), respectively. Rats fed onion- and apple-enriched diets had increased abundance of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus spp., enhanced SCFAs (acetic, propionic, isobutyric, and valeric acids), decreased excretion of some BAs, mainly of the primary (CA, α-MCA, and ß-MCA) and secondary type (ω-MCA, HDCA, NCA, DCA, and LCA), and increased amount of taurine- and glycine-conjugated BAs compared to the OC group. The contribution of specific bioactive compounds and their metabolites in the regulation of the microbiome and the pathways linked to SCFA and BA formation and their relationship with some diseases needs further research.

Effect of Chromium Nanoparticles and Switching from a High-Fat to a Low-Fat Diet on the Cecal Microenvironment in Obese Rats.

Previous studies showed that chromium nanoparticles (Cr-NPs) might be used as dietary compounds against some obesity-related disorders; however, there is little information on how these compounds influence the gut microenvironment. The aim of this study was to investigate whether the negative effects of a high-fat diet in the large intestine of rats might be mitigated by switching to a low-fat diet and supplementation with Cr-NPs. Microbiota sequencing analysis revealed that the main action of the Cr-NPs was focused on changing the gut microbiota's activity. Supplementation with nanoparticles decreased the activity of ß-glucuronidase and enzymes responsible for the hydrolysis of dietary oligosaccharides and, thus, lowered the concentration of short-chain fatty acids in the cecum. In this group, there was also an elevated level of cecal lithocholic acid. The most favorable effect on the regulation of obesity-related disorders was observed when a high-fat diet was switched to a low-fat diet. This dietary change enhanced the production of short-chain fatty acids, reduced the level of secondary bile acids, and increased the microbial taxonomic richness, microbial differences, and microbial enzymatic activity in the cecum. To conclude, supplementation of a high-fat diet with Cr-NPs primarily had an effect on intestinal microbial activity, but switching to a low-fat diet had a powerful, all-encompassing effect on the gut that improved both microbial activity and composition.

The Role of Microbiota-Derived Metabolites in Colorectal Cancer.

The impact of bacterial members of the microbiota on the development of colorectal cancer (CRC) has become clear in recent years. However, exactly how bacteria contribute to the development of cancer is often still up for debate. The impact of bacteria-derived metabolites, which can influence the development of CRC either in a promoting or inhibiting manner, is undeniable. Here, we discuss the effects of the most well-studied bacteria-derived metabolites associated with CRC, including secondary bile acids, short-chain fatty acids, trimethylamine-N-oxide and indoles. We show that the effects of individual metabolites on CRC development are often nuanced and dose- and location-dependent. In the coming years, the array of metabolites involved in CRC development will undoubtedly increase further, which will emphasize the need to focus on causation and mechanisms and the clearly defined roles of bacterial species within the microbiota.

Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease.

Atherosclerotic cardiovascular disease (ASCVD) is the primary cause of death globally, with nine million deaths directly attributable to ischemic heart diseases in 2020. Since the last few decades, great effort has been put toward primary and secondary prevention strategies through identification and treatment of major cardiovascular risk factors, including hypertension, diabetes, dyslipidemia, smoking, and a sedentary lifestyle. Once labelled "the forgotten organ", the gut microbiota has recently been rediscovered and has been found to play key functions in the incidence of ASCVD both directly by contributing to the development of atherosclerosis and indirectly by playing a part in the occurrence of fundamental cardiovascular risk factors. Essential gut metabolites, such as trimethylamine N-oxide (TMAO), secondary bile acids, lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs), have been associated with the extent of ischemic heart diseases. This paper reviews the latest data on the impact of the gut microbiome in the incidence of ASCVD.