Project description:Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the concept of enterotypes, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into functional, ecological and medical contexts. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.
Project description:The human gut microbiome has been linked to health and disease. Investigation of the human microbiome has largely employed 16S amplicon sequencing, with limited ability to distinguish microbes at the species level. Herein, we describe the development of Reference-based Exact Mapping (RExMap) of microbial amplicon variants that enables mapping of microbial species from standard 16S sequencing data. RExMap analysis of 16S data captures ∼75% of microbial species identified by whole-genome shotgun sequencing, despite hundreds-fold less sequencing depth. RExMap re-analysis of existing 16S data from 29,349 individuals across 16 regions from around the world reveals a detailed landscape of gut microbial species across populations and geography. Moreover, RExMap identifies a core set of fifteen gut microbes shared by humans. Core microbes are established soon after birth and closely associate with BMI across multiple independent studies. RExMap and the human microbiome dataset are presented as resources with which to explore the role of the human microbiome.
Project description:Transcriptomic analysis of PD-L1 positive and negative hot lung adenocarcinomas identifies a different molecular immunogenic landscape
Project description:Inter-individual variability in the microbial gene complement encoding for carbohydrate-active enzymes (CAZymes) can profoundly regulate how the host interacts with diverse carbohydrate sources thereby influencing host health. CAZy-typing, characterizing the microbiota-associated CAZyme-coding genes within a host individual, can be a useful tool to predict carbohydrate pools that the host can metabolize, or identify which CAZyme families are underrepresented requiring supplementation via microbiota transplantation or probiotics. CAZy-typing, moreover, provides a novel framework to search for disease biomarkers. As a proof of concept, we used publicly available metagenomes (935) representing 310 type strain bacterial genomes to establish the link between disease status and CAZymes in the oral and gut microbial ecosystem. The abundance and distribution of 220 recovered CAZyme families in saliva and stool samples from patients with colorectal cancer, rheumatoid arthritis, and type 1 diabetes were compared with healthy subjects. Based on the multivariate discriminant analysis, the disease phenotype did not alter the CAZyme profile suggesting a functional conservation in carbohydrate metabolism in a disease state. When disease and healthy CAZyme profiles were contrasted in differential analysis, CAZyme markers that were underrepresented in type 1 diabetes (15), colorectal cancer (12), and rheumatoid arthritis (5) were identified. Of interest, are the glycosyltransferase which can catalyze the synthesis of glycoconjugates including lipopolysaccharides with the potential to trigger inflammation, a common feature in many diseases. Our analysis has also confirmed the expansive carbohydrate metabolism in the gut as evidenced by the overrepresentation of CAZyme families in the gut compared to the oral site. Nevertheless, each site exhibited specific CAZyme markers. Taken together, our analysis provides an insight into the CAZyme landscape in health and disease and has demonstrated the diversity in carbohydrate metabolism in host-microbiota which can be a sound basis for optimizing the selection of pre, pro, and syn-biotic candidate products.
Project description:BackgroundTyping analysis has become a popular approach to categorize individual differences in studies of animal gut microbial communities. However, previous definitions of gut microbial types were more understood as a passive reaction process to different external interferences, as most studies involve diverse environmental variables. We wondered whether distinct gut microbial types can also occur in animals under the same external environment. Moreover, the role of host sex in shaping gut microbiota has been widely reported; thus, the current study preliminarily explores the effects of sex on potential different microbial types.MethodsHere, adult striped hamsters Cricetulus barabensis of different sexes were housed under the same controlled laboratory conditions, and their fecal samples were collected after two months to assess the gut microbiota by 16S rRNA sequencing.ResultsThe gut microbiota of captive striped hamsters naturally separated into two types at the amplicon sequence variant (ASV) level. There was a significant difference in the Shannon index among these two types. A receiver operating characteristic (ROC) curve showed that the top 30 ASVs could effectively distinguish each type. Linear discriminant analysis of effect size (LEfSe) showed enrichment of the genera Lactobacillus, Treponema and Pygmaiobacter in one gut microbial type and enrichment of the genera Turicibacter and Ruminiclostridium in the other. The former type had higher carbohydrate metabolism ability, while the latter harbored a more complex co-occurrence network and higher amino acid metabolism ability. The gut microbial types were not associated with sex; however, we did find sex differences in the relative abundances of certain bacterial taxa, including some type-specific sex variations.ConclusionsAlthough captive animals live in a unified environment, their gut bacteria can still differentiate into distinct types, but the sex of the hosts may not play an important role in the typing process of small-scale captive animal communities. The relevant driving factors as well as other potential types need to be further investigated to better understand host-microbe interactions.