Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, had no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, was demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA in NAFLD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) confirmed the critical role of gut microbiota in OCA treatment for NAFLD by effectively alleviating histopathological lesions and restoring liver function impaired by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia muciniphila, Bifidobacterium spp., Bacteroides spp., Alistipes spp., Lactobacillus spp., Streptococcus thermophilus, and Parasutterella excrementihominis. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing levels of serum hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of serum-conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the HFD-fed mice. Strong correlations were observed between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched by OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) mainly responsible for primary bile acid deconjugation. In conclusion, this study demonstrated that OCA intervention altered gut microbiota composition with specially enriched gut microbes modulating host bile acids, thus effectively alleviating NAFLD in the mice.

Tibetan pigs (TPs) can adapt to the extreme environments in the Tibetan plateau implicated by their self-genome signals, but little is known about roles of the gut microbiota in the host adaption. Here, we reconstructed 8210 metagenome-assembled genomes from TPs (n = 65) living in high-altitude and low-altitude captive pigs (87 from China—CPs and 200 from Europe—EPs) that were clustered into 1050 species-level genome bins (SGBs) at the threshold of 95% average nucleotide identity. 73.47% of SGBs represented new species. The gut microbial community structure analysis based on 1,048 SGBs showed that TPs was significantly different from low-altitude captive pigs. TP-associated SGBs enabled to digest multiple complex polysaccharides, including cellulose, hemicellulose, chitin and pectin. Especially, we found TPs showed the most common enrichment of phyla Fibrobacterota and Elusimicrobia, which were involved in the productions of short- and medium-chain fatty acids (acetic acid, butanoate and propanoate; octanomic, decanoic and dodecanoic acids), as well as in the biosynthesis of lactate, 20 essential amino acids, multiple B vitamins (B1, B2, B3, B5, B7 and B9) and cofactors. Unexpectedly, Fibrobacterota solely showed powerful metabolic capacity, including the synthesis of acetic acid, alanine, histidine, arginine, tryptophan, serine, threonine, valine, B2, B5, B9, heme and tetrahydrofolate. These metabolites might contribute to host adaptation to high-altitude, such as energy harvesting and resistance against hypoxia and ultraviolet radiation. This study provides insights into understanding the role of gut microbiome played in mammalian high-altitude adaptation and discovers some potential microbes as probiotics for improving animal health.

This study aimed to evaluate the effects of Saccharomyces cerevisiae, and their combination on rumen fermentation and growth performance of heat-stressed goats. Twelve heat-stressed goats (20.21 ± 2.30 kg) were divided equally into four groups: control group (CG, fed the basal diet, Saccharomyces cerevisiae supplemented group (SC, 0.60% Saccharomyces cerevisiae added to the basal diet), Clostridium butyricum supplemented group (CB, 0.05% Clostridium butyricum added to the basal diet), and their combination supplemented group (COM 0.60% Saccharomyces cerevisiae and 0.05% Clostridium butyricum added to the basal diet) and were assigned to a 4 × 3 incomplete Latin square design. The rumen fluid and feces were collected for fermentation parameters and feed digestibility analysis, and animal growth performance was also assessed during all the experiment periods. The results showed that rumen pH, rumen cellulolytic enzymes (avicelase, CMCaes, cellobiase, and xylanase) activities, and the concentrations of rumen total volatile fatty acid (TVFA), acetic acid, and propionic acid were significantly increased with Saccharomyces cerevisiae, Clostridium butyricum, and their combination supplementation (p < 0.05). Besides, the dry matter intake (DMI), average daily gain (ADG), and the digestibility of dry matter (DM), neutral detergent fiber (NDF), and acidic detergent fiber (ADF) were significantly increased (p < 0.05) with supplemented these probiotics. However, the ammonia nitrogen (NH₃-N) concentration only significantly increased in CB and A/P ratio (acetic acid to propionic acid ratio) only significantly increased in SC and CB. These results indicated that the supplementation with these probiotics could ameliorate rumen fermentation and growth performance of heat-stressed goats.

This study was performed to explore the predominant responses of rumen microbiota with thymol supplementation as well as effective dose of thymol on rumen fermentation. Thymol at different concentrations, i.e., 0, 100 mg/L, 200 mg/L, and 400 mg/L (four groups × five replications) was applied for 24 h of fermentation in a rumen fluid incubation system. Illumina MiSeq sequencing was applied to investigate the ruminal microbes in addition to the examination of rumen fermentation. Thymol doses reached 200 mg/L and significantly decreased (p < 0.05) total gas production (TGP) and methane production; the production of total volatile fatty acids (VFA), propionate, and ammonia nitrogen, and the digestibility of dry matter and organic matter were apparently decreased (p < 0.05) when the thymol dose reached 400 mg/L. A thymol dose of 200 mg/L significantly affected (p < 0.05) the relative abundance of 14 genera of bacteria, three species of archaea, and two genera of protozoa. Network analysis showed that bacteria, archaea, and protozoa significantly correlated with methane production and VFA production. This study indicates an optimal dose of thymol at 200 mg/L to facilitate rumen fermentation, the critical roles of bacteria in rumen fermentation, and their interactions with the archaea and protozoa.

Objective: Colorectal adenomas (CRA) are the primary precancerous lesions leading to colorectal cancer (CRC). Early detection and intervention of CRA can significantly reduce the incidence of CRC. We investigated the relationships between the gut microbiome and the expression levels of PD-L1, IL-6, and IFN-γ at different CRA stages.Methods: Participants were divided into normal, non-advanced adenoma (NAA), and advanced adenoma (AA) groups. PD-L1 expression in collected tissues was analyzed via immunohistochemistry (IHC) and Western blotting. Serum IL-6 and IFN-γ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). 16S rRNA gene sequencing was used to examine gut microbiota changes, with correlation analysis to assess microbial influences on CRA progression.Results: The main differences in bacterial composition among the three groups were found within the Firmicutes and Bacteroidetes phyla. In the normal vs. NAA comparison, Clostridium sensu stricto, Faecalimonas, Gemmiger, and Ruminococcus were more abundant in the normal group, while Solobacterium was enriched in the NAA group. For the normal vs. AA comparison, the normal group was enriched with Anaerostipes, Blautia, Clostridium sensu stricto, Intestinibacter, Phocaeicola, and Turicibacter, whereas Solobacterium was more abundant in the AA group. In the NAA vs. AA comparison, the NAA group exhibited higher levels of Blautia, Faecalimonas, and Turicibacter relative to the AA group. Anaerostipes and Blautia are positively correlated with taurine and hypotaurine metabolism, propanoate metabolism, and zeatin biosynthesis. PD-L1 protein levels progressively increase with CRA advancement. Additionally, Faecalimonas, and Solobacterium were negatively associated with IFN-γ, while Gemmiger, and Anaerostipes were positively associated with IL-6.Conclusion: This study highlights the dynamic alterations in gut microbiota composition and their potential influence on the regulation of inflammatory cytokines and PD-L1 expression during CRA progression. The enrichment of protective taxa, such as Anaerostipes and Blautia, in the normal group emphasizes their potential role in mitigating adenoma progression. Dietary modulation to promote the proliferation of these beneficial bacteria could serve as a promising strategy to improve colorectal health. Future research should further explore the specific relationships between dietary components, gut microbiota, and metabolic pathways, and assess the effects of dietary interventions on gut health.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease with no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, has been demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA to NALFD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) confirmed the critical role of gut microbiota in OCA treatment to NALFD which could effectively alleviate histopathological traits and damaged liver function induced by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia miciniphila, Bacteroides massiliensis, Streptococcus thermophilus, and Bifidobacterium spp. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing the levels of hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of hydrophilic conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the serum of HFD-fed mice. Strong correlations were found between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched in OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) responsible for primary bile acids synthesis. In conclusion, the current study demonstrated that OCA intervention altered gut microbiota composition, thus enriching special gut microbes modulating dynamic homeostasis of bile acids which ultimately influenced therapeutic effects on NAFLD.