Function Of Human Gut Microbiota Research Articles

Role of Simulated Nannochloropsis gaditana Digests in Shaping Gut Microbiota and Short-Chain Fatty Acid Levels.

The connection between gut microbiota and factors like diet is crucial for maintaining intestinal balance, which in turn impacts the host's overall health. Nannochloropsis gaditana microalgae is a sustainable source of bioactive compounds, mainly known for its used in aquaculture and extraction of bioactive lipids, with potential health benefits whose effects on human gut microbiota are still unknown. Therefore, the goal of this work was to assess the impact of N. gaditana on human gut microbiota composition and derived metabolites by combining the INFOGEST protocol and in vitro colonic fermentation process to evaluate potential effects on human gut microbiota conformation through 16S rRNA gene sequencing and its metabolic functionality. The results have demonstrated the ability of the digests from N. gaditana to significantly modify gut microbiota composition, promoting an increase in beneficial bacterial genera such as Akkermansia, Butyricicoccus, Eisenbergiella, Lachnoclostridium, and Marvinbryantia, in contrast to inulin, after 48 h of colonic fermentation. Additionally, the digests increased the levels of both major and minor short-chain fatty acids (SCFAs), particularly butyric and valeric acids, considered as intestinal biomarkers, and increased ammonium production. This research has demonstrated, for the first time, the potential of N. gaditana microalgae as a sustainable agent for influencing the composition and functionality of human gut microbiota.

Data-independent acquisition boosts quantitative metaproteomics for deep characterization of gut microbiota

Metaproteomics can provide valuable insights into the functions of human gut microbiota (GM), but is challenging due to the extreme complexity and heterogeneity of GM. Data-independent acquisition (DIA) mass spectrometry (MS) has been an emerging quantitative technique in conventional proteomics, but is still at the early stage of development in the field of metaproteomics. Herein, we applied library-free DIA (directDIA)-based metaproteomics and compared the directDIA with other MS-based quantification techniques for metaproteomics on simulated microbial communities and feces samples spiked with bacteria with known ratios, demonstrating the superior performance of directDIA by a comprehensive consideration of proteome coverage in identification as well as accuracy and precision in quantification. We characterized human GM in two cohorts of clinical fecal samples of pancreatic cancer (PC) and mild cognitive impairment (MCI). About 70,000 microbial proteins were quantified in each cohort and annotated to profile the taxonomic and functional characteristics of GM in different diseases. Our work demonstrated the utility of directDIA in quantitative metaproteomics for investigating intestinal microbiota and its related disease pathogenesis.

Distinct composition and metabolic functions of human gut microbiota are associated with cachexia in lung cancer patients

Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

An in vitro evaluation of the effects of different statins on the structure and function of human gut bacterial community.

Statins, a class of drugs that can effectively remove cholesterol from serum, are used to regulate plasma total cholesterol and reduce the risk of cardiovascular diseases, but it is still unclear whether the drug are modulated by gut microbiota or the structures of gut microbiota are shaped by statins. We investigated the interactions between statins and the human gut microbiota during the in vitro fermentation process by 16S rRNA gene sequencing, gas chromatography (GC), and high-performance liquid chromatography (HPLC) analyses. The presence of fluvastatin (FLU2) specifically promoted the growth of Escherichia/Shigella, Ruminococcaceae UCG 014, and Sutterella. However, the composition of the gut bacterial microbiota remained relatively static in samples treated with rosuvastatin (ROS), simvastatin (SIM), and atorvastatin (ATO). The PICRUSt program predicted moderate differences in the functional categories related to the biosynthesis of other secondary metabolites, cellular processes and signaling, and signal transduction in the FLU2 fermentation samples. Our study revealed substantial variation in the structure and function of microbiomes from the FLU2-treated samples. In addition, short-chain fatty acids (SCFAs) were also significantly decreased in FLU2-treated samples compared with the samples treated with other stains. Statins can be degraded by the human gut microbiota in vitro, and the degradation rate was approximately 7%–30% and 19%–48% after fermentation was allowed to proceed for 24 h and 48 h, respectively. Generally, FLU2 could largely shape the composition and function of human gut microbiota, which resulted in changes in the production of SCFAs. In turn, all statins could be degraded or modified by the gut microbiota. Our study paves the way for elucidating statin-gut microbiota interactions in vitro towards the improvement of the host health and personalized medicine.

Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life

BackgroundEstablishment of the human gut microbiota begins at birth. This early-life microbiota development can impact host physiology during infancy and even across an entire life span. However, the functional stability and population structure of the gut microbiota during initial colonization remain poorly understood. Metaproteomics is an emerging technology for the large-scale characterization of metabolic functions in complex microbial communities (gut microbiota).ResultsWe applied a metagenome-informed metaproteomic approach to study the temporal and inter-individual differences of metabolic functions during microbial colonization of preterm human infants’ gut. By analyzing 30 individual fecal samples, we identified up to 12,568 protein groups for each of four infants, including both human and microbial proteins. With genome-resolved matched metagenomics, proteins were confidently identified at the species/strain level. The maximum percentage of the proteome detected for the abundant organisms was ~45%. A time-dependent increase in the relative abundance of microbial versus human proteins suggested increasing microbial colonization during the first few weeks of early life. We observed remarkable variations and temporal shifts in the relative protein abundances of each organism in these preterm gut communities. Given the dissimilarity of the communities, only 81 microbial EggNOG orthologous groups and 57 human proteins were observed across all samples. These conserved microbial proteins were involved in carbohydrate, energy, amino acid and nucleotide metabolism while conserved human proteins were related to immune response and mucosal maturation. We identified seven proteome clusters for the communities and showed infant gut proteome profiles were unstable across time and not individual-specific. Applying a gut-specific metabolic module (GMM) analysis, we found that gut communities varied primarily in the contribution of nutrient (carbohydrates, lipids, and amino acids) utilization and short-chain fatty acid production.ConclusionsOverall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.

Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

Gut microbiota and gastrointestinal health: current concepts and future directions

The microbial community of the human gut - the enteric microbiota - plays a critical role in functions that sustain health and is a positive asset in host defenses. In recent years, our understanding of this so-called human 'super organism' has advanced, following characterization of fecal metagenomes which identified three core bacterial enterotypes, and based on basic and clinical research into the impact and consequences of microbiota biodiversity and change on gastrointestinal disorders and diseases. This article considers current knowledge and future perspectives on the make-up and function of human gut microbiota, with a particular focus on altered microbiota and gastrointestinal disorders, nutritional influences on the gut microbiota, and the consequences for gastrointestinal health, as well as improved understanding of gut-microbiota-brain communication.

Storage conditions of intestinal microbiota matter in metagenomic analysis

BackgroundThe structure and function of human gut microbiota is currently inferred from metagenomic and metatranscriptomic analyses. Recovery of intact DNA and RNA is therefore a critical step in these studies. Here, we evaluated how different storage conditions of fecal samples affect the quality of extracted nucleic acids and the stability of their microbial communities.ResultsWe assessed the quality of genomic DNA and total RNA by microcapillary electrophoresis and analyzed the bacterial community structure by pyrosequencing the 16S rRNA gene. DNA and RNA started to fragment when samples were kept at room temperature for more than 24 h. The use of RNAse inhibitors diminished RNA degradation but this protection was not consistent among individuals. DNA and RNA degradation also occurred when frozen samples were defrosted for a short period (1 h) before nucleic acid extraction. The same conditions that affected DNA and RNA integrity also altered the relative abundance of most taxa in the bacterial community analysis. In this case, intra-individual variability of microbial diversity was larger than inter-individual one.ConclusionsThough this preliminary work explored a very limited number of parameters, the results suggest that storage conditions of fecal samples affect the integrity of DNA and RNA and the composition of their microbial community. For optimal preservation, stool samples should be kept at room temperature and brought at the laboratory within 24 h after collection or be stored immediately at −20°C in a home freezer and transported afterwards in a freezer pack to ensure that they do not defrost at any time. Mixing the samples with RNAse inhibitors outside the laboratory is not recommended since proper homogenization of the stool is difficult to monitor.

Review: Tools for the tract: understanding the functionality of the gastrointestinal tract

The human gastrointestinal tract comprises a series of complex and dynamic organs ranging from the stomach to the distal colon, which harbor immense microbial assemblages that are known to be vital for human health. Until recently, most of the details concerning our gut microbiota remained obscure. Over the past several years, however, a number of crucial technological and conceptual innovations have been introduced to shed more light on the composition and functionality of human gut microbiota. Recently developed high throughput approaches, including next-generation sequencing technologies and phylogenetic microarrays targeting ribosomal RNA gene sequences, allow for comprehensive analysis of the diversity and dynamics of the gut microbiota composition. Nevertheless, most of the microbes especially in the human large intestine still remain uncultured, and the in situ functions of distinct groups of the gut microbiota are therefore largely unknown, but pivotal to the understanding of their role in human physiology. Apart from functional and metagenomics approaches, stable isotope probing is a promising tool to link the metabolic activity and diversity of microbial communities, including yet uncultured microbes, in a complex environment. Advancements in current stable isotope probing approaches integrated with the application of high-throughput diagnostic microarray-based phylogenetic profiling and metabolic flux analysis should facilitate the understanding of human microbial ecology and will enable the development of innovative strategies to treat or prevent intestinal diseases of as yet unknown etiology.