Bacterial biogeography of the human digestive tract.
Ontology highlight
ABSTRACT:
SUBMITTER: Stearns JC
PROVIDER: S-EPMC3240969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As a long-standing biomedical model, rats have been frequently used in studies exploring the correlations between gastrointestinal (GI) bacterial biota and diseases. In the present study, luminal and mucosal samples taken along the longitudinal axis of the rat digestive tract were subjected to 16S rRNA gene sequencing-based analysis to determine the baseline microbial composition. Results showed that the community diversity increased from the upper to lower GI segments and that the stratification of microbial communities as well as shift of microbial metabolites were driven by biogeographic location. A greater proportion of lactate-producing bacteria (such as Lactobacillus, Turicibacter and Streptococcus) were found in the stomach and small intestine, while anaerobic Lachnospiraceae and Ruminococcaceae, fermenting carbohydrates and plant aromatic compounds, constituted the bulk of the large-intestinal core microbiota where topologically distinct co-occurrence networks were constructed for the adjacent luminal and mucosal compartments. When comparing the GI microbiota from different hosts, we found that the rat microbial biogeography might represent a new reference, distinct from other murine animals. Our study provides the first comprehensive characterization of the rat GI microbiota landscape for the research community, laying the foundation for better understanding and predicting the disease-related alterations in microbial communities.
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Project description:Mucins are a family of heavily glycosylated proteins that are the major organic components of the mucus layer, the protective layer covering the epithelial cells in many human and animal organs, including the entire gastro-intestinal tract. Microbes that can associate with mucins benefit from this interaction since they can get available nutrients, experience physico-chemical protection and adhere, resulting in increased residence time. Mucin-degrading microorganisms, which often are found in consortia, have not been extensively characterized as mucins are high molecular weight glycoproteins that are hard to study because of their size, complexity and heterogeneity. The purpose of this review is to discuss how advances in mucus and mucin research, and insight in the microbial ecology promoted our understanding of mucin degradation. Recent insight is presented in mucin structure and organization, the microorganisms known to use mucin as growth substrate, with a specific attention on Akkermansia muciniphila, and the molecular basis of microbial mucin degradation owing to availability of genome sequences.
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Project description:The aerodigestive tract (ADT) is the primary portal through which pathogens and other invading microbes enter the body. As the direct interface with the environment, we hypothesize that the ADT microbiota possess biosynthetic gene clusters (BGCs) for antibiotics and other specialized metabolites to compete with both endogenous and exogenous microbes. From 1,214 bacterial genomes, representing 136 genera and 387 species that colonize the ADT, we identified 3,895 BGCs. To determine the distribution of BGCs and bacteria in different ADT sites, we aligned 1,424 metagenomes, from nine different ADT sites, onto the predicted BGCs. We show that alpha diversity varies across the ADT and that each site is associated with distinct bacterial communities and BGCs. We identify specific BGC families enriched in the buccal mucosa, external naris, gingiva, and tongue dorsum despite these sites harboring closely related bacteria. We reveal BGC enrichment patterns indicative of the ecology at each site. For instance, aryl polyene and resorcinol BGCs are enriched in the gingiva and tongue, which are colonized by many anaerobes. In addition, we find that streptococci colonizing the tongue and cheek possess different ribosomally synthesized and posttranslationally modified peptide BGCs. Finally, we highlight bacterial genera with BGCs but are underexplored for specialized metabolism and demonstrate the bioactivity of Actinomyces against other bacteria, including human pathogens. Together, our results demonstrate that specialized metabolism in the ADT is extensive and that by exploring these microbiomes further, we will better understand the ecology and biogeography of this system and identify new bioactive natural products. IMPORTANCE Bacteria produce specialized metabolites to compete with other microbes. Though the biological activities of many specialized metabolites have been determined, our understanding of their ecology is limited, particularly within the human microbiome. As the aerodigestive tract (ADT) faces the external environment, bacteria colonizing this tract must compete both among themselves and with invading microbes, including human pathogens. We analyzed the genomes of ADT bacteria to identify biosynthetic gene clusters (BGCs) for specialized metabolites. We found that the majority of ADT BGCs are uncharacterized and the metabolites they encode are unknown. We mapped the distribution of BGCs across the ADT and determined that each site is associated with its own distinct bacterial community and BGCs. By further characterizing these BGCs, we will inform our understanding of ecology and biogeography across the ADT, and we may uncover new specialized metabolites, including antibiotics.
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Project description:Bacterial communities of the bovine digestive tract
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Project description:The digestive tract of triatomines (DTT) is an ecological niche favored by microbiota whose enzymatic profile is adapted to the specific substrate availability in this medium. This report describes the molecular enzymatic properties that promote bacterial prominence in the DTT. The microbiota composition was assessed previously based on 16S ribosomal DNA, and whole sequenced genomes of bacteria from the same genera were used to calculate the GC level of rare and prominent bacterial species in the DTT. The enzymatic reactions encoded by coding sequences of both rare and common bacterial species were then compared and revealed key functions explaining why some genera outcompete others in the DTT. Representativeness of DTT microbiota was investigated by shotgun sequencing of DNA extracted from bacteria grown in liquid Luria-Bertani broth (LB) medium. Results showed that GC-rich bacteria outcompete GC-poor bacteria and are the dominant components of the DTT microbiota. In addition, oxidoreductases are the main enzymatic components of these bacteria. In particular, nitrate reductases (anaerobic respiration), oxygenases (catabolism of complex substrates), acetate-CoA ligase (tricarboxylic acid cycle and energy metabolism), and kinase (signaling pathway) were the major enzymatic determinants present together with a large group of minor enzymes including hydrogenases involved in energy and amino acid metabolism. In conclusion, despite their slower growth in liquid LB medium, bacteria from GC-rich genera outcompete the GC-poor bacteria because their specific enzymatic abilities impart a selective advantage in the DTT.
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Project description:AimTo clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses.MethodsThe present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16(INK4a) expression in HPV-positive and HPV-negative cases was also made.ResultsHPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P < 0.001). There was a significant difference in the geographical distribution of HPV16-E6 variants. Multiple infections of different HPV types were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16(INK4a) proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and -negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs.ConclusionBased on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.
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Project description:Cancers of the digestive tract are among the most prevalent types of cancer. These types of cancers are often diagnosed at a late stage, which results in a poor prognosis. Currently, many biomedical studies focus on the role of ion channels, in particular transient receptor potential (TRP) channels, in cancer pathophysiology. TRP channels show mostly non-selective permeability to monovalent and divalent cations. TRP channels are often dysregulated in digestive tract cancers, which can result in alterations of cancer hallmark functions, such as enhanced proliferation, migration, invasion and the inability to induce apoptosis. Therefore, TRP channels could serve as potential diagnostic biomarkers. Moreover, TRP channels are mostly expressed on the cell surface and ion channel targeting drugs do not need to enter the cell, making them attractive candidate drug targets. In this review, we summarize the current knowledge about TRP channels in connection to digestive tract cancers (oral cancer, esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer) and give an outlook on the potential of TRP channels as cancer biomarkers or therapeutic targets.
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