The signaling pathway of hypoxia inducible factor in regulating gut homeostasis.

Hypoxia represent a condition in which an adequate amount of oxygen supply is missing in the body, and it could be caused by a variety of diseases, including gastrointestinal disorders. This review is focused on the role of hypoxia in the maintenance of the gut homeostasis and related treatment of gastrointestinal disorders. The effects of hypoxia on the gut microbiome and its role on the intestinal barrier functionality are also covered, together with the potential role of hypoxia in the development of gastrointestinal disorders, including inflammatory bowel disease and irritable bowel syndrome. Finally, we discussed the potential of hypoxia-targeted interventions as a novel therapeutic approach for gastrointestinal disorders. In this review, we highlighted the importance of hypoxia in the maintenance of the gut homeostasis and the potential implications for the treatment of gastrointestinal disorders.

Beyond cellulose: pharmaceutical potential for bioactive plant polysaccharides in treating disease and gut dysbiosis.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

High Antioxidant Capacity of Lacticaseibacillus paracasei TDM-2 and Pediococcus pentosaceus TCM-3 from Qinghai Tibetan Plateau and Their Function towards Gut Modulation.

Probiotic supplementation is a key therapeutic strategy for promoting gut health and maintaining gut homeostasis by modulating functional microbiota. In this study, we isolated two lactic acid bacteria (LAB) strains, Pediococcus pentosaceus TCM-3 and Lacticaseibacillus paracasei TDM-2, from Qinghai-Tibetan plateau, and evaluated their probiotic properties and antioxidant bioactivity. In which, TDM-2 had higher T-AOC activity than either TCM-3 or LGG (4.10 µmol/mL vs. 3.68 and 3.53 µmol/mL, respectively, p < 0.05). These strains have shown high antioxidant activity compared to the LAB strains and were found to be acid and bile salt tolerant, confronting the safety issues of antibiotic resistance and the capability of surviving in simulated gastric and intestinal juices. In vitro fermentation experiments with human gut microbiota revealed significant differences in microbial community composition between samples supplemented with TCM-3 and TDM-2 and those without. The addition of these two strains resulted in an enrichment of beneficial taxa, such as the Pediococcus, Lactobacillus, and Clostridium_sensu_strictos at the genus level, and Firmicutes and Proteobacteria at the phylum level. Notably, the TCM-3 group exhibited higher short-chain fatty acid production than the TDM-2 group and untreated controls (acetic acid at 12 h: 4.54 mmol L-1 vs. 4.06 mmol L-1 and 4.00 mmol L-1; acetic acid at 24 h: 4.99 mmol L-1 vs. 4.90 mmol L-1 and 4.82 mmol L-1, p < 0.05). These findings demonstrate that LAB supplementation with high antioxidant capacity and probiotic properties can promote gut health by modulating functional microbiota and is enriching for beneficial taxa. Our study provides guidance for therapeutic strategies that use novel LAB strains to maintain gut homeostasis and functional microbiota modulation.

Simulated seasonal diets alter yak rumen microbiota structure and metabolic function.

Yak is the only ruminant on the Qinghai-Tibetan Plateau that grazes year-round. Although previous research has shown that yak rumen microbiota fluctuates in robust patterns with seasonal foraging, it remains unclear whether these dynamic shifts are driven by changes in environment or nutrient availability. The study examines the response of yak rumen microbiota (bacteria, fungi, and archaea) to simulated seasonal diets, excluding the contribution of environmental factors. A total of 18 adult male yaks were randomly divided into three groups, including a nutrition stress group (NSG, simulating winter pasture), a grazing simulation group (GSG, simulating warm season pasture), and a supplementation group (SG, simulating winter pasture supplemented with feed concentrates). Volatile fatty acids (VFAs) profiling showed that ruminal acetate, propionate and total VFA contents were significantly higher (p < 0.05) in GSG rumen. Metagenomic analysis showed that Bacteroidetes (53.9%) and Firmicutes (37.1%) were the dominant bacterial phyla in yak rumen across dietary treatments. In GSG samples, Actinobacteriota, Succinivibrionaceae_UCG-002, and Ruminococcus albus were the most abundant, while Bacteroides was significantly more abundant in NSG samples (p < 0.05) than that in GSG. The known fiber-degrading fungus, Neocallimastix, was significantly more abundant in NSG and SG samples, while Cyllamyces were more prevalent in NSG rumen than in the SG rumen. These findings imply that a diverse consortium of microbes may cooperate in response to fluctuating nutrient availability, with depletion of known rumen taxa under nutrient deficiency. Archaeal community composition showed less variation between treatments than bacterial and fungal communities. Additionally, Orpinomyces was significantly positively correlated with acetate levels, both of which are prevalent in GSG compared with other groups. Correlation analysis between microbial taxa and VFA production or between specific rumen microbes further illustrated a collective response to nutrient availability by gut microbiota and rumen VFA metabolism. PICRUSt and FUNGuild functional prediction analysis indicated fluctuation response of the function of microbial communities among groups. These results provide a framework for understanding how microbiota participate in seasonal adaptations to forage availability in high-altitude ruminants, and form a basis for future development of probiotic supplements to enhance nutrient utilization in livestock.