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

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

The Food-gut Human Axis: The Effects of Diet on Gut Microbiota and Metabolome

Current Medicinal Chemistry ◽

10.2174/0929867324666170428103848 ◽

2019 ◽

Vol 26 (19) ◽

pp. 3567-3583 ◽

Cited By ~ 18

Author(s):

Maria De Angelis ◽

Gabriella Garruti ◽

Fabio Minervini ◽

Leonilde Bonfrate ◽

Piero Portincasa ◽

...

Keyword(s):

Gut Microbiota ◽

Human Health ◽

Dietary Habits ◽

Short Chain Fatty Acids ◽

Human Organism ◽

Immune Functions ◽

Intestinal Microbes ◽

Dietary Components ◽

Dietary Treatments ◽

The Relationship

Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influence the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota.

Download Full-text

Mutually Beneficial Symbiosis Between Human and Gut-Dominant Bacteroides Species Through Bacterial Assimilation of Host Mucosubstances

10.1101/2020.08.21.262261 ◽

2020 ◽

Author(s):

Masahiro Sato ◽

Kanta Kajikawa ◽

Tomoya Kumon ◽

Daisuke Watanabe ◽

Ryuichi Takase ◽

...

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Health Promotion ◽

Gut Microbiota ◽

Human Health ◽

Short Chain Fatty Acids ◽

Essential Amino Acids ◽

Fasting State ◽

Human Gut ◽

Human Host

AbstractThe composition of gut microbiota is influenced by the quantity and type of nutrients in host. Even with some Bacteroides species being categorized as pathogens, Bacteroides is one of the most dominant gut bacteria. Here we indicate the physiological determinants of the species of Bacteroides for being dominant in human gut microbiota. Each of the host extracellular mucosubstances including glycosaminoglycans (GAGs) and mucin has grown human gut microbiota. In spite of the differences among initial microbiota profiles, Bacteroides species dominated the community when GAG (e.g., chondroitin sulfate or hyaluronan) was used as a sole carbon source. In fact, GAGs and the Bacteroides genes which are vital for the degradation of GAGs were commonly detected in human feces. Mucin has encouraged the growth of Bacteroides and several other genera. A comprehensive analysis on the degradation and assimilation of mucosubstances by the genus Bacteroides using around 30 species has shown that most species degrade and assimilate GAGs and mucin, showing that Bacteroides species can survive even in the undernutrition condition including the fasting state. In the assimilation of GAG or mucin, Bacteroides species significantly secreted essential amino acids, γ-amino butyrate (GABA), and/or short-chain fatty acids which are needed for human health. This is the first report as regards mutually beneficial interaction between human and Bacteroides species via bacterial assimilation of host mucosubstances and secretion of metabolites for host health promotion.SignificanceThe genus Bacteroides is one of the most dominant gut bacteria, although its beneficial effects on human health have not been well understood. Here, we show modes of action in human-Bacteroides interrelationship. Mucosubstances including GAGs and mucin secreted by human host are abundant in gut for microbiota to grow well. Bacteroides species are dominant in the community in the presence of GAGs, and provide human host with a considerable amount of essential amino acids, γ-amino butyrate, and short-chain fatty acids produced from mucosubstances. These results postulate mutually beneficial symbiosis system between human and Bacteroides through bacterial assimilation of host mucosubstances and secretion of metabolites for human body and mental health promotion even in the undernutrition condition including the fasting state.

Download Full-text

Relationship between Nutrient Intake and Human Gut Microbiota in Monozygotic Twins

Medicina ◽

10.3390/medicina57030275 ◽

2021 ◽

Vol 57 (3) ◽

pp. 275

Author(s):

Natsuko Matsumoto ◽

Jonguk Park ◽

Rie Tomizawa ◽

Hitoshi Kawashima ◽

Koji Hosomi ◽

...

Keyword(s):

Individual Differences ◽

Environmental Factors ◽

Gut Microbiota ◽

Human Health ◽

Negative Correlation ◽

Nutrient Intake ◽

Monozygotic Twins ◽

Human Gut ◽

Positive Correlation ◽

Human Gut Microbiota

Background and Objectives: The gut microbiota is associated with human health and dietary nutrition. Various studies have been reported in this regard, but it is difficult to clearly analyze human gut microbiota as individual differences are significant. The causes of these individual differences in intestinal microflora are genetic and/or environmental. In this study, we focused on differences between identical twins in Japan to clarify the effects of nutrients consumed on the entire gut microbiome, while excluding genetic differences. Materials and Methods: We selected healthy Japanese monozygotic twins for the study and confirmed their zygosity by matching 15 short tandem repeat loci. Their fecal samples were subjected to 16S rRNA sequencing and bioinformatics analyses to identify and compare the fluctuations in intestinal bacteria. Results: We identified 12 genera sensitive to environmental factors, and found that Lactobacillus was relatively unaffected by environmental factors. Moreover, we identified protein, fat, and some nutrient intake that can affect 12 genera, which have been identified to be more sensitive to environmental factors. Among the 12 genera, Bacteroides had a positive correlation with retinol equivalent intake (rs = 0.38), Lachnospira had a significantly negative correlation with protein, sodium, iron, vitamin D, vitamin B6, and vitamin B12 intake (rs = −0.38, −0.41, −0.39, −0.63, −0.42, −0.49, respectively), Lachnospiraceae ND3007 group had a positive correlation with fat intake (rs = 0.39), and Lachnospiraceae UCG-008 group had a negative correlation with the saturated fatty acid intake (rs = −0.45). Conclusions: Our study is the first to focus on the relationship between human gut microbiota and nutrient intake using samples from Japanese twins to exclude the effects of genetic factors. These findings will broaden our understanding of the more intuitive relationship between nutrient intake and the gut microbiota and can be a useful basis for finding useful biomarkers that contribute to human health.

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

Does Consumption of Fermented Foods Modify the Human Gut Microbiota?

Journal of Nutrition ◽

10.1093/jn/nxaa077 ◽

2020 ◽

Vol 150 (7) ◽

pp. 1680-1692 ◽

Cited By ~ 3

Author(s):

Leah T Stiemsma ◽

Reine E Nakamura ◽

Jennifer G Nguyen ◽

Karin B Michels

Keyword(s):

Gut Microbiota ◽

Human Health ◽

Food Consumption ◽

Intervention Studies ◽

Fermented Food ◽

Fermented Foods ◽

Human Intervention ◽

Human Gut ◽

Gut Dysbiosis ◽

Human Gut Microbiota

ABSTRACT The human microbiota is a key contributor to many aspects of human health and its composition is largely influenced by diet. There is a growing body of scientific evidence to suggest that gut dysbiosis (microbial imbalance of the intestine) is associated with inflammatory and immune-mediated diseases (e.g., inflammatory bowel disease and asthma). Regular consumption of fermented foods (e.g., kimchi, kefir, etc.) may represent a potential avenue to counter the proinflammatory effects of gut dysbiosis. However, an assessment of the available literature in this research area is lacking. Here we provide a critical review of current human intervention studies that analyzed the effect of fermented foods on the composition and/or function of the human gut microbiota. A total of 19 human intervention studies were identified that met this search criteria. In this review, we discuss evidence that consumption of fermented foods may modify the gut microbiota in humans. Further, there is cursory evidence to suggest that gut microbiota compositional changes mediate associations between fermented food consumption and human health outcomes. Although promising, there remains considerable heterogeneity in the human populations targeted in the intervention studies we identified. Larger longitudinal feeding studies with longer follow-up are necessary to confirm and enhance the current data. Further, future studies should consider analyzing microbiota function as a means to elucidate the mechanism linking fermented food consumption with human health. This review highlights methodologic considerations for intervention trials, emphasizing an expanse of research opportunities related to fermented food consumption in humans.

Download Full-text

Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

Microorganisms ◽

10.3390/microorganisms7100456 ◽

2019 ◽

Vol 7 (10) ◽

pp. 456 ◽

Cited By ~ 9

Author(s):

Kaliyan Barathikannan ◽

Ramachandran Chelliah ◽

Momna Rubab ◽

Eric Banan-Mwine Daliri ◽

Fazle Elahi ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Molecular Mechanisms ◽

Short Chain Fatty Acids ◽

Genetic Profile ◽

Fecal Transplantation ◽

Intestinal Microbes ◽

Prevalence Of Obesity ◽

Future Direction ◽

The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

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

Rett Syndrome and Other Neurodevelopmental Disorders Share Common Changes in Gut Microbial Community: A Descriptive Review

International Journal of Molecular Sciences ◽

10.3390/ijms20174160 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4160 ◽

Cited By ~ 6

Author(s):

Elisa Borghi ◽

Aglaia Vignoli

Keyword(s):

Microbial Community ◽

Gut Microbiota ◽

Rett Syndrome ◽

Neurodevelopmental Disorders ◽

Short Chain Fatty Acids ◽

Dynamic Effects ◽

Common Pathway ◽

Gut Microbial Community ◽

Host Metabolism

In this narrative review, we summarize recent pieces of evidence of the role of microbiota alterations in Rett syndrome (RTT). Neurological problems are prominent features of the syndrome, but the pathogenic mechanisms modulating its severity are still poorly understood. Gut microbiota was recently demonstrated to be altered both in animal models and humans with different neurodevelopmental disorders and/or epilepsy. By investigating gut microbiota in RTT cohorts, a less rich microbial community was identified which was associated with alterations of fecal microbial short-chain fatty acids. These changes were positively correlated with severe clinical outcomes. Indeed, microbial metabolites can play a crucial role both locally and systemically, having dynamic effects on host metabolism and gene expression in many organs. Similar alterations were found in patients with autism and down syndrome as well, suggesting a potential common pathway of gut microbiota involvement in neurodevelopmental disorders.

Download Full-text