Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as Akkermansia muciniphila, Lactobacillus, and Bifidobacterium. In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. Akkermansia muciniphila is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.

Rex rabbit is an important small herbivore for fur and meat production. However, little is known about the gut microbiota in rex rabbit, especially regarding their relationship with different fecal types and growth of the hosts. We characterized the microbiota of both hard and soft feces from rex rabbits with high and low body weight by using the Illumina MiSeq platform targeting the V4 region of the 16S rDNA. High weight rex rabbits possess distinctive microbiota in hard feces, but not in soft feces, from the low weight group. We detected the overrepresentation of several genera such as YS2/Cyanobacteria and Bacteroidales and underrepresentation of genera such as Anaeroplasma spp. and Clostridiaceae in high weight hard feces. Between fecal types, several bacterial taxa such as Ruminococcaceae, and Akkermansia spp. were enriched in soft feces. PICRUSt analysis revealed that metabolic pathways such as “stilbenoid, diarylheptanoid, gingerol biosynthesis” were enriched in high weight rabbits and pathways related to “xenobiotics biodegradation” and “various types of N-glycan biosynthesis” were overrepresented in rabbit soft feces. Our study provides foundation to generate hypothesis aiming to test the roles that different bacterial taxa play in the growth and caecotrophy of rex rabbits.

Captive breeding has been used as an effective approach to protecting endangered animals but its effect on the gut microbiome and the conservation status of these species is largely unknown. The giant panda is a flagship species for the conservation of wildlife. With integrated efforts including captive breeding, this species has been recently upgraded from “endangered” to “vulnerable” (IUCN 2016). Since a large proportion (21.8%) of their global population is still captive, it is critical to understand how captivity changes the gut microbiome of these pandas and how such alterations to the microbiome might affect their future fitness and potential impact on the ecosystem after release into the wild. Here, we use 16S rRNA (ribosomal RNA) marker gene sequencing and shotgun metagenomics sequencing to demonstrate that the fecal microbiomes differ substantially between wild and captive giant pandas. Fecal microbiome diversity was significantly lower in captive pandas, as was the diversity of functional genes. Additionally, captive pandas have reduced functional potential for cellulose degradation but enriched metabolic pathways for starch metabolism, indicating that they may not adapt to a wild diet after being released into the wild since a major component of their diet in the wild will be bamboo. Most significantly, we observed a significantly higher level of amylase activity but a lower level of cellulase activity in captive giant panda feces than those of wild giant pandas, shown by an in vitro experimental assay. Furthermore, antibiotic resistance genes and virulence factors, as well as heavy metal tolerance genes were enriched in the microbiomes of captive pandas, which raises a great concern of spreading these genes to other wild animals and ecosystems when they are released into a wild environment. Our results clearly show that captivity has altered the giant panda microbiome, which could have unintended negative consequences on their adaptability and the ecosystem during the reintroduction of giant pandas into the wild.

Microbial communities of human gut directly influence health and bear adaptive potential to different geography environment and lifestyles. However, knowledge about the influences of altitude and geography on the gut microbiota of Tibetans is currently limited. In this study, fecal microbiota from 208 Tibetans across six different locations were analyzed by MiSeq sequencing; these locations included Gannan, Gangcha, Tianzhu, Hongyuan, Lhasa and Nagqu, with altitudes above sea level ranging from 2800 m to 4500 m across the Tibetan plateau. Significant differences were observed in microbial diversity and richness in different locations. At the phylum level, gut populations of Tibetans comprised Bacteroidetes (60.00%), Firmicutes (29.04%), Proteobacteria (5.40%), and Actinobacteria (3.85%) and were marked by a low ratio (0.48) of Firmicutes to Bacteroidetes. Analysis based on operational taxonomic unit level revealed that core microbiotas included Prevotella, Faecalibacterium, and Blautia, whereas Prevotella predominated all locations, except Gangcha. Four community state types were detected in all samples, and they mainly belong to Prevotella, Bacteroides, and Ruminococcaceae. Principal component analysis and related correspondence analysis results revealed that bacterial profiles in Tibetan guts varied significantly with increasing altitude, BMI, and age, and facultative anaerobes were rich in Tibetan guts. Gut microbiota may play important roles in regulating high-altitude and geographical adaptations.

This study set out to investigate the relationship between gut microbiota composition and host adaptation to high altitude conditions. Fecal samples from both high and low altitude humans and pigs were studied using multi-omics methods. 16S ribosomal meta-analysis results showed significant differences in bacterial diversity and composition between high and low altitude members of the same species, as well as between different species. Acinetobacter, Pseudomonas, and Sphingobacterium were the three most abundant bacterial genera found in high altitude fecal samples of both humans and pigs. The alpha diversities of microbiota from Chinese people were found to be relatively lower than those of people in other countries. We found significant convergent trends in microbial metagenome compositions between Tibetans and Tibetan pigs living at high altitudes, and significant differences between these and their low-altitude counterparts. Metabolic pathways related to energy metabolism, amino-acid metabolism, and carbohydrate metabolism were consistently enriched at high altitudes, in both Tibetans and Tibetan pigs. Propanoic acid and octadecanoic acid were significantly elevated in high-altitude Tibetan pigs, and genes related to these two metabolites were also up-regulated. Thus, this study revealed that unique gut bacteriomes and their functions may be closely related to environmental host adaptation in high altitude conditions, such as those in the Tibetan plateau.