Biomarkers of human gut microbiota diversity and dysbiosis

The association of gut microbiota dysbiosis with various human diseases is being substantiated with increasing evidence. Metabolites derived from both, microbiota and the human host play a central role in disease susceptibility and disease progression by extensively modulating host physiology and metabolism. Several of these metabolites have the potential to serve as diagnostic biomarkers for monitoring disease states in conjunction with intestinal microbiota dysbiosis. In this narrative review we evaluate the potential of trimethylamine-N-oxide, short-chain fatty acids, 3-indoxyl sulfate, p-cresyl sulfate, secondary bile acids, hippurate, human β-defensin-2, chromogranin A, secreted immunoglobulins and zonulin to serve as biomarkers for metabolite profiling and diagnostic suitability for dysbiosis and disease.

Download Full-text

Gut microbiota: The emerging link to lung homeostasis and disease

Journal of Bacteriology ◽

10.1128/jb.00454-20 ◽

2020 ◽

Cited By ~ 1

Author(s):

An Zhou ◽

Yuanyuan Lei ◽

Li Tang ◽

Shiping Hu ◽

Min Yang ◽

...

Keyword(s):

Gut Microbiota ◽

Cross Talk ◽

Lung Diseases ◽

Disease Susceptibility ◽

Short Chain Fatty Acids ◽

Therapeutic Strategies ◽

Point Of View ◽

Health And Disease ◽

Gut Microbiota Dysbiosis ◽

Underlying Pathogenesis

The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated that the gut microbiota could affect pulmonary health and disease through cross-talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also vary by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs as well as elucidate the underlying pathogenesis or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.

Download Full-text

Nitric Oxide Impacts Human Gut Microbiota Diversity and Functionalities

mSystems ◽

10.1128/msystems.00558-21 ◽

2021 ◽

Author(s):

Marion Leclerc ◽

Cassandre Bedu-Ferrari ◽

Lucie Etienne-Mesmin ◽

Mahendra Mariadassou ◽

Lucie Lebreuilly ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Response ◽

Gut Microbiota ◽

Inflammatory Diseases ◽

Human Gut ◽

Human Gut Microbiota ◽

Microbiota Diversity ◽

Gut Microbiota Dysbiosis

Gut microbiota dysbiosis has been associated with inflammatory diseases. The human inflammatory response leads to an overproduction of nitric oxide (NO) in the gut.

Download Full-text

The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyz061 ◽

2019 ◽

Vol 23 (1) ◽

pp. 26-41 ◽

Cited By ~ 3

Author(s):

Shan Li ◽

Dongyu Hua ◽

Qiaoyan Wang ◽

Ling Yang ◽

Xinlei Wang ◽

...

Keyword(s):

Fatty Acids ◽

Chronic Pain ◽

Gut Microbiota ◽

Reference Lists ◽

Short Chain Fatty Acids ◽

Research Progress ◽

Abnormal Behaviors ◽

Gut Microbiota Dysbiosis ◽

Secondary Bile Acids

Abstract Background Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the “microbiota–gut–brain” axis. Methods PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included “pain OR chronic pain” AND “gut microbiota OR metabolites”; “depression OR depressive disorder” AND “gut microbiota OR metabolites”. We also searched the reference lists of key articles manually. Results This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. Conclusion Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.

Download Full-text

Structural Change of Gut Microbiota in Patients with Post-Stroke Comorbid Cognitive Impairment and Depression and Its Correlation with Clinical Features

Journal of Alzheimer s Disease ◽

10.3233/jad-200315 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1595-1608

Author(s):

Yi Ling ◽

Qilu Gu ◽

Junmei Zhang ◽

Tianyu Gong ◽

Xiongpeng Weng ◽

...

Keyword(s):

Cognitive Impairment ◽

Gut Microbiota ◽

Critical Role ◽

Area Under The Curve ◽

Short Chain Fatty Acids ◽

Diagnostic Biomarkers ◽

Linear Discriminant ◽

Post Stroke ◽

Non Invasive ◽

Gut Microbiota Dysbiosis

Background: Post-stroke comorbid cognitive impairment and depression (PSCCID) is a severe neuropsychiatric complication after acute stroke. Gut microbiota dysbiosis is associated with many psychiatric disorders. Alterations in the composition of gut microbiota may serve as a critical role in patients with PSCCID. Objective: We aimed to characterize the microbial profiles of patients with PSCCID. Method: A total of 175 stroke patients were recruited in the study. The composition of gut bacterial communities of patients was determined by 16S ribosomal RNA Miseq sequencing, and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used to demonstrate the functional alterations of gut microbiota. We further identified the characteristic gut microbiota of PSCCID using linear discriminant analysis effect size. Results: Patients with PSCCID exhibited an increased abundance of Proteobacteria, including Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae, and a decreased abundance of several short-chain fatty acids-producing bacteria compared with non-PSCCID patients. The abundance of Gammaproteobacteria and Enterobacteriaceae showed negative correlations with the MoCA score. Moreover, the Kyoto Encyclopedia of Genes and Genomes results demonstrated the enriched orthologs of glycan biosynthesis and metabolism and decreased orthologs of amino acid metabolism in PSCCID patients. Importantly, the characteristic gut microbiota was identified and achieved an area under the curve of 0.847 between the two groups. Conclusion: In this study, we characterized the gut microbiota of PSCCID patients, and revealed the correlations of the altered gut microbiota with clinical parameters, which took a further step towards non-invasive diagnostic biomarkers for PSCCID from fecal samples.

Download Full-text

Microbiota-Associated Metabolites and Related Immunoregulation in Colorectal Cancer

Cancers ◽

10.3390/cancers13164054 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4054

Author(s):

Yan Chen ◽

Ying-Xuan Chen

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Gut Microbiota ◽

Immune Responses ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Indole Derivatives ◽

Human Gut ◽

Growing Body ◽

Specific Influence

A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.

Download Full-text

Gut Microbiota Dysbiosis Associated With Altered Production of Short Chain Fatty Acids in Children With Neurodevelopmental Disorders

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.00223 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 2

Author(s):

Katarina Bojović ◽

Ður -d ica Ignjatović ◽

Svetlana Soković Bajić ◽

Danijela Vojnović Milutinović ◽

Mirko Tomić ◽

...

Keyword(s):

Fatty Acids ◽

Gut Microbiota ◽

Neurodevelopmental Disorders ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Gut Microbiota Dysbiosis ◽

Chain Fatty Acids

Download Full-text

Dietary Fatty Acids Sustain the Growth of the Human Gut Microbiota

Applied and Environmental Microbiology ◽

10.1128/aem.01525-18 ◽

2018 ◽

Vol 84 (21) ◽

Cited By ~ 21

Author(s):

Richard Agans ◽

Alex Gordon ◽

Denise Lynette Kramer ◽

Sergio Perez-Burillo ◽

José A. Rufián-Henares ◽

...

Keyword(s):

Fatty Acids ◽

Small Intestine ◽

Fatty Acid ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Dietary Fatty Acids ◽

Dietary Fats ◽

High Fat ◽

Human Gut ◽

Content Type

ABSTRACTWhile a substantial amount of dietary fats escape absorption in the human small intestine and reach the colon, the ability of resident microbiota to utilize these dietary fats for growth has not been investigated in detail. In this study, we used anin vitromultivessel simulator system of the human colon to reveal that the human gut microbiota is able to utilize typically consumed dietary fatty acids to sustain growth. Gut microbiota adapted quickly to a macronutrient switch from a balanced Western diet-type medium to its variant lacking carbohydrates and proteins. We defined specific genera that increased in their abundances on the fats-only medium, includingAlistipes,Bilophila, and several genera of the classGammaproteobacteria. In contrast, the abundances of well-known glycan and protein degraders, includingBacteroides,Clostridium, andRoseburiaspp., were reduced under such conditions. The predicted prevalences of microbial genes coding for fatty acid degradation enzymes and anaerobic respiratory reductases were significantly increased in the fats-only environment, whereas the abundance of glycan degradation genes was diminished. These changes also resulted in lower microbial production of short-chain fatty acids and antioxidants. Our findings provide justification for the previously observed alterations in gut microbiota observed in human and animal studies of high-fat diets.IMPORTANCEIncreased intake of fats in many developed countries has raised awareness of potentially harmful and beneficial effects of high fat consumption on human health. Some dietary fats escape digestion in the small intestine and reach the colon where they can be metabolized by gut microbiota. We show that human gut microbes are able to maintain a complex community when supplied with dietary fatty acids as the only nutrient and carbon sources. Such fatty acid-based growth leads to lower production of short-chain fatty acids and antioxidants by community members, which potentially have negative health consequences on the host.

Download Full-text

The Prebiotic Inulin Beneficially Alters the Gut Microbiome and Associated Metabolites in an APOE4 Mouse Model (P08-133-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-133-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Lucille Yanckello ◽

Jared Hoffman ◽

Ishita Parikh ◽

Jessie Hoffman ◽

Stefan Green ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Dietary Intervention ◽

Disease Risk ◽

Short Chain Fatty Acids ◽

Apoe4 Allele ◽

Funding Sources ◽

Tryptophan Metabolites ◽

Host Metabolism ◽

Microbiota Diversity

Abstract Objectives The APOE4 allele is a genetic risk factor for certain diseases, due in part to alterations in lipid and glucose metabolism. The gut microbiota is also known to impact metabolic and can be beneficially modulated by prebiotics. Prebiotics are fermented into metabolites by the gut microbiota. These metabolites act as gut-brain axis components. However, the interaction of the APOE4 allele, gut microbiota, and prebiotics are unknown. The goal of the study was to use prebiotic diet to restore the gut microbiome of mice with human APOE4 (E4FAD) genes. We hypothesized that the microbial compositions of E4 mice fed inulin, compared to control fed, will correlate to metabolites being produced by the microbiome that confer benefit to host metabolism. Methods At 3 months of age the E4FAD mice were fed for 4 months with either control or inulin diet. We used 16S rRNA sequencing to determine gut microbiota diversity and species variations; non-targeted UPLC-MS/MS and GC-MS analysis was used to determine metabolic profiles of blood. Results The inulin fed mice showed a more beneficial microbial taxa profile than those mice that were control fed. Control mice showed higher levels of dimethylglycine, choline, creatine and the polyamine spermine. Higher levels of spermine, specifically, correlate to higher levels of the Proteobacteria which has been implicated in GI disorders. E4 inulin fed mice showed higher levels of bile acids, short chain fatty acids and metabolites involved in energy, increased levels of tryptophan metabolites and robust increases in sphingomyelins. Specifically in E4 inulin fed mice we saw increases in certain genera of bacteria, all of which have been implicated in being beneficial to the composition of the microbiome and producing one or more of the above mentioned metabolites. Conclusions We believe the disparities of microbial metabolite production between E4 inulin fed mice and E4 control fed mice can be attributed to differences in certain taxa that produce these metabolites, and that higher levels of these taxa are due to the dietary intervention of inulin. Despite the APOE4 allele increasing one's risk for certain diseases, we believe that beneficially modulating the gut microbiota may be one way to enhance host metabolism and decrease disease risk over time. Funding Sources NIH/NIDDK T323048107792, NIH/NIA R01AG054459, NIEHS/NIH P42ES007380. Supporting Tables, Images and/or Graphs

Download Full-text

Prebiotics and Community Composition Influence Gas Production of the Human Gut Microbiota

mBio ◽

10.1128/mbio.00217-20 ◽

2020 ◽

Vol 11 (5) ◽

Author(s):

Xiaoqian Yu ◽

Thomas Gurry ◽

Le Thanh Tu Nguyen ◽

Hunter S. Richardson ◽

Eric J. Alm

Keyword(s):

Fatty Acids ◽

Chemical Composition ◽

Gut Microbiota ◽

Community Composition ◽

Human Body ◽

Ex Vivo ◽

Short Chain Fatty Acids ◽

Gas Production ◽

Human Gut ◽

Human Gut Microbiota

ABSTRACT Prebiotics confer benefits to human health, often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short-chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a by-product of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota are affected by the chemical composition of the prebiotic and the community composition of the microbiota. We first constructed a linear system model based on mass and electron balance and compared the theoretical product ranges of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while interindividual differences in H2 production during inulin degradation were driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production, will depend more on substrate, while rare metabolisms such as methanogenesis depend more strongly on microbiome composition. IMPORTANCE Prebiotic fermentation in the gut often leads to the coproduction of short-chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely considered during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production were strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production were less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

Download Full-text

Dietary Components, Microbial Metabolites and Human Health: Reading between the Lines

Foods ◽

10.3390/foods9081045 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1045

Author(s):

Yao Guo ◽

Xiaohan Bian ◽

Jiali Liu ◽

Ming Zhu ◽

Lin Li ◽

...

Keyword(s):

Linoleic Acid ◽

Gut Microbiota ◽

Human Health ◽

Kynurenic Acid ◽

Molecular Mechanisms ◽

Eating Habits ◽

Short Chain Fatty Acids ◽

Human Gut ◽

Dietary Components ◽

Host Metabolism

Trillions of bacteria reside in the human gut and they metabolize dietary substances to obtain nutrients and energy while producing metabolites. Therefore, different dietary components could affect human health in various ways through microbial metabolism. Many such metabolites have been shown to affect human physiological activities, including short-chain fatty acids metabolized from carbohydrates; indole, kynurenic acid and para-cresol, metabolized from amino acids; conjugated linoleic acid and linoleic acid, metabolized from lipids. Here, we review the features of these metabolites and summarize the possible molecular mechanisms of their metabolisms by gut microbiota. We discuss the potential roles of these metabolites in health and diseases, and the interactions between host metabolism and the gut microbiota. We also show some of the major dietary patterns around the world and hope this review can provide insights into our eating habits and improve consumers’ health conditions.

Download Full-text