肠道微生物调控宿主食欲的研究进展

肠道微生物与宿主代谢相互作用,可调节机体的生理功能。宿主机体中存在"微生物-肠道-大脑轴",肠道菌群可通过多种途径影响中枢神经系统,进而对宿主摄食等行为产生影响。食物中不易被宿主消化吸收的膳食纤维等营养物质,被肠道微生物发酵可产生多种代谢产物,这些代谢产物作为信号分子可通过不同途径介导中枢神经系统,进而调控宿主食欲。本文主要综述了肠道微生物及其代谢产物对中枢神经系统与宿主食欲的影响及其可能的调控途径与机制,以加深肠道微生物在调控宿主食欲方面的新认识。     

The effect of captivity on the primate gut microbiome varies with host dietary niche

Despite careful attention to animal nutrition and wellbeing, gastrointestinal distress remains relatively common in captive non‐human primates (NHPs), particularly dietary specialists such as folivores. These patterns may be a result of marked dietary differences between captive and wild settings and associated impacts on the gut microbiome. However, given that most existing studies target NHP dietary specialists, it is unclear if captive environments have distinct impacts on the gut microbiome of NHPs with different dietary niches. To begin to examine this question, we used 16S ribosomal RNA gene amplicon sequences to compare the gut microbiomes of five NHP genera categorized either as folivores (Alouatta, Colobus) or non‐folivores (Cercopithecus, Gorilla, Pan) sampled both in captivity and in the wild. Though captivity affected the gut microbiomes of all NHPs in this study, the effects were largest in folivorous NHPs. Shifts in gut microbial diversity and in the relative abundances of fiber‐degrading microbial taxa suggest that these findings are driven by marked dietary shifts for folivorous NHPs in captive settings. We propose that zoos and other captive care institutions consider including more natural browse in folivorous NHP diets and regularly bank fecal samples to further explore the relationship between NHP diet, the gut microbiome, and health outcomes.     

肠道微生物组与宿主的表观遗传修饰

高通量测序技术已经增加了人们对肠道微生物组和表观遗传学修饰的理解,将肠道微生物组和宿主表观遗传学修饰紧密联系起来,阐明了很多疾病的发生过程如免疫、代谢、心血管疾病甚至是癌症。肠道微生物组与宿主具有相互作用,与人体密不可分,相辅相成。肠道微生物组的生态失调可能诱导疾病的发生并能调控宿主表观遗传学修饰。宿主表观遗传学调控和肠道微生物组(或其代谢产物)变化的相互关系在很多疾病中都有报道。因此,肠道微生物组可作为某些疾病的诊断标记,健康肠道微生物组的移植会逆转这种微生态失调,可作为一种有效的治疗策略。本文主要探讨了肠道微生物组直接调控宿主表观修饰和通过小分子生物活性物质和其他酶辅因子间接影响表观修饰,以及基于肠道微生物组调控宿主表观修饰的诊断和治疗应用等。     

Unravelling the effects of the environment and host genotype on the gut microbiome

To what extent do host genetics control the composition of the gut microbiome? Studies comparing the gut microbiota in human twins and across inbred mouse lines have yielded inconsistent answers to this question. However, candidate gene approaches, in which one gene is deleted or added to a model host organism, show that a single host gene can have a tremendous effect on the diversity and population structure of the gut microbiota. Now, quantitative genetics is emerging as a highly promising approach that can be used to better understand the overall architecture of host genetic influence on the microbiota, and to discover additional host genes controlling microbial diversity in the gut. In this Review, we describe how host genetics and the environment shape the microbiota, and how these three factors may interact in the context of chronic disease.     

NAD precursors cycle between host tissues and the gut microbiome

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Mammalian gut metabolomes mirror microbiome composition and host phylogeny

In the past decade, studies on the mammalian gut microbiome have revealed that different animal species have distinct gut microbial compositions. The functional ramifications of this variation in microbial composition remain unclear: do these taxonomic differences indicate microbial adaptations to host-specific functionality, or are these diverse microbial communities essentially functionally redundant, as has been indicated by previous metagenomics studies? Here, we examine the metabolic content of mammalian gut microbiomes as a direct window into ecosystem function, using an untargeted metabolomics platform to analyze 101 fecal samples from a range of 25 exotic mammalian species in collaboration with a zoological center. We find that mammalian metabolomes are chemically diverse and strongly linked to microbiome composition, and that metabolome composition is further correlated to the phylogeny of the mammalian host. Specific metabolites enriched in different animal species included modified and degraded host and dietary compounds such as bile acids and triterpenoids, as well as fermentation products such as lactate and short-chain fatty acids. Our results suggest that differences in microbial taxonomic composition are indeed translated to host-specific metabolism, indicating that taxonomically distant microbiomes are more functionally diverse than redundant.Subject terms: Metabolomics, Microbiome, Microbial ecology     

A single genus in the gut microbiome reflects host preference and specificity

Delineating differences in gut microbiomes of human and animal hosts contributes towards understanding human health and enables new strategies for detecting reservoirs of waterborne human pathogens. We focused upon Blautia, a single microbial genus that is important for nutrient assimilation as preliminary work suggested host-related patterns within members of this genus. In our dataset of 57 M sequence reads of the V6 region of the 16S ribosomal RNA gene in samples collected from seven host species, we identified 200 high-resolution taxonomic units within Blautia using oligotyping. Our analysis revealed 13 host-specific oligotypes that occurred exclusively in fecal samples of humans (three oligotypes), swine (six oligotypes), cows (one oligotype), deer (one oligotype), or chickens (two oligotypes). We identified an additional 171 oligotypes that exhibited differential abundance patterns among all the host species. Blautia oligotypes in the human population obtained from sewage and fecal samples displayed remarkable continuity. Oligotypes from only 10 Brazilian human fecal samples collected from individuals in a rural village encompassed 97% of all Blautia oligotypes found in a Brazilian sewage sample from a city of three million people. Further, 75% of the oligotypes in Brazilian human fecal samples matched those in US sewage samples, implying that a universal set of Blautia strains may be shared among culturally and geographically distinct human populations. Such strains can serve as universal markers to assess human fecal contamination in environmental samples. Our results indicate that host-specificity and host-preference patterns of organisms within this genus are driven by host physiology more than dietary habits.     

Micro-coevolution of host genetics with gut microbiome in three Chinese ethnic groups

Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies. To gain insight into the interactions between host genetic variation and the gut microbiome, we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups, Uyghur, Kazakh, and Han Chinese. We found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition, functional composition, enterotype stratification, and microbiome genetic differentiation. We also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial species. Notably, interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human phenotypes. Bacteroides ovatus, previously reported to modulate intestinal immunity, is significantly correlated with the host genetic variant rs12899811 (meta-P = 5.55 × 10⁻⁵), which regulates the VPS33B expression in the colon, acting as a tumor suppressor of colorectal cancer. These results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity.     

Evaluating supervised and unsupervised background noise correction in human gut microbiome data

The ability to predict human phenotypes and identify biomarkers of disease from metagenomic data is crucial for the development of therapeutics for microbiome-associated diseases. However, metagenomic data is commonly affected by technical variables unrelated to the phenotype of interest, such as sequencing protocol, which can make it difficult to predict phenotype and find biomarkers of disease. Supervised methods to correct for background noise, originally designed for gene expression and RNA-seq data, are commonly applied to microbiome data but may be limited because they cannot account for unmeasured sources of variation. Unsupervised approaches address this issue, but current methods are limited because they are ill-equipped to deal with the unique aspects of microbiome data, which is compositional, highly skewed, and sparse. We perform a comparative analysis of the ability of different denoising transformations in combination with supervised correction methods as well as an unsupervised principal component correction approach that is presently used in other domains but has not been applied to microbiome data to date. We find that the unsupervised principal component correction approach has comparable ability in reducing false discovery of biomarkers as the supervised approaches, with the added benefit of not needing to know the sources of variation apriori. However, in prediction tasks, it appears to only improve prediction when technical variables contribute to the majority of variance in the data. As new and larger metagenomic datasets become increasingly available, background noise correction will become essential for generating reproducible microbiome analyses.     

膳食脂肪、肠道微生物与宿主健康的研究进展

作为三大主要营养物质之一,膳食脂肪为人体提供能量和营养。膳食脂肪摄入不当会破坏肠道微生物的稳态,影响宿主的代谢状况,增加慢性疾病发生的风险。建立疾病动物模型是研究肠道微生物与宿主健康的重要手段。文中综述了膳食脂质的数量和种类、肠道微生物和宿主代谢之间的相互作用及其可能的作用机制,阐述了基于不同的疾病动物模型,膳食脂质影响肠道微生物的结构和功能,以及对宿主代谢的调节,为深入了解膳食脂质、肠道微生态和宿主健康三者之间的关系提供了依据。     

Adaptation of gut microbiome and host metabolic systems to lignocellulosic degradation in bamboo rats

Bamboo rats (Rhizomys pruinosus) are among the few mammals that lives on a bamboo-based diet which is mainly composed of lignocellulose. However, the mechanisms of adaptation of their gut microbiome and metabolic systems in the degradation of lignocellulose are largely unknown. Here, we conducted a multi-omics analysis on bamboo rats to investigate the interaction between their gut microbiomes and metabolic systems in the pre- and post-weaning periods, and observed significant relationships between dietary types, gut microbiome, serum metabolome and host gene expression. For comparison, published gut microbial data from the famous bamboo-eating giant panda (Ailuropoda melanoleuca) were also used for analysis. We found that the adaptation of the gut microbiome of the bamboo rat to a lignocellulose diet is related to a member switch in the order Bacteroidales from family Bacteroidaceae to family Muribaculaceae, while for the famous bamboo-eating giant panda, several aerobes and facultative anaerobes increase after weaning. The conversion of bacteria with an increased relative abundance in bamboo rats after weaning enriched diverse carbohydrate-active enzymes (CAZymes) associated with lignocellulose degradation and functionally enhanced the biosynthesis of amino acids and B vitamins. Meanwhile, the circulating concentration of short-chain fatty acids (SCFAs) derived metabolites and the metabolic capacity of linoleic acid in the host were significantly elevated. Our findings suggest that fatty acid metabolism, including linoleic acid and SCFAs, are the main energy sources for bamboo rats in response to the low-nutrient bamboo diet.Subject terms: Metagenomics, Bacterial evolution     

蝗虫肠道微生物研究进展

蝗虫自古以来是我国农林牧业的一大害虫,蝗虫聚集成灾对农业造成了巨大的损失,国内外学者也因此对其进行了深入的研究。随着科研工作者对昆虫肠道微生态学理论的逐渐重视,蝗虫的肠道微生物也成为了研究的重点,同时测序技术的迅速发展促进了蝗虫肠道微生物的研究。本文从蝗虫肠道菌群的多样性、功能及研究方法入手,对近年来蝗虫肠道微生物的研究进展进行总结,并对今后的研究进行展望。     

Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet

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Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice

Background

Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way.

Results

We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites. A high-fat diet (HFD) intervention resulted in a rapid and significant increase in the intestinal BA pool within 12 h, followed by an alteration in microbial composition at 24 h, providing supporting evidence that BAs are major dietary factors regulating gut microbiota. Feeding mice with BAs along with a normal diet induced an obese phenotype and obesity-associated gut microbial composition, similar to HFD-fed mice. Inhibition of hepatic BA biosynthesis under HFD conditions attenuated the HFD-induced gut microbiome alterations. Both inhibition of BAs and direct suppression of microbiota improved obese phenotypes.

Conclusions

Our study highlights a liver–BA–gut microbiome metabolic axis that drives significant modifications of BA and microbiota compositions capable of triggering metabolic disorders, suggesting new therapeutic strategies targeting BA metabolism for metabolic diseases.