scholarly journals Contribution of Gut Microbiome to Human Health and the Metabolism or Toxicity of Drugs and Natural Products

2021 ◽  
Author(s):  
Prasat Kittakoop
Keyword(s):  
Natural Products ◽  
Gut Microbiota ◽  
Human Health ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Therapeutic Efficiency ◽  
Drug Candidates ◽  
Disease States ◽  
Metabolic Activities ◽  
Toxicity Of Drugs

Trillions of microorganisms with a complex and diverse community are in the human gastrointestinal tract. Gut microbial genomes have much more genes than human genome, thus having a variety of enzymes for many metabolic activities; therefore, gut microbiota is recognized as an “organ” that has essential functions to human health. There are interactions between host and gut microbiome, and there are correlations between gut microbiome in the healthy state and in certain disease states, such as cancer, liver diseases, diabetes, and obesity. Gut microbiota can produce metabolites from nutrients of dietary sources and from drug metabolisms; these metabolites, for example, short-chain fatty acids (SCFAs), have substantial effects on human health. Drug-microbiome interactions play a crucial role in therapeutic efficiency. Some drugs are able to change compositions of gut microbiota, which can lead to either enhance or reduce therapeutic efficiency. This chapter provides an overview of roles of gut microbiota in human health and diseases and recent research studies on the metabolism or toxicity of drugs and natural products. Since gut bacteria considerably contribute to drug metabolism, research on the influence of gut microbiome on drug candidates (or natural products) should be part of the drug development processes.

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

2019 ◽  
Vol 26 (19) ◽  
pp. 3567-3583 ◽  
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.

scholarly journals Guild-based analysis for understanding gut microbiome in human health and diseases

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guojun Wu ◽  
Naisi Zhao ◽  
Chenhong Zhang ◽  
Yan Y. Lam ◽  
Liping Zhao
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Gut Microbiome ◽  
Association Studies ◽  
Causative Role ◽  
Disease Phenotypes ◽  
Genetic Complexity ◽  
Causative Agents ◽  
Specific Health

AbstractTo demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.

scholarly journals Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stefano Romano ◽  
George M. Savva ◽  
Janis R. Bedarf ◽  
Ian G. Charles ◽  
Falk Hildebrand ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
Meta Analysis ◽  
Gastrointestinal Symptoms ◽  
Short Chain Fatty Acids ◽  
Inflammatory Status

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

scholarly journals Probiotic: An Uprising Human Health Concept

2021 ◽  
Author(s):  
Amishi Bhatt ◽  
Dhyey Kothari ◽  
Charmy Kothari ◽  
Ramesh Kothari
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Scientific Evidence ◽  
Vital Role ◽  
Health Food ◽  
Food Industries ◽  
Health Concept ◽  
Agricultural Applications ◽  
Potential Applications ◽  
Metabolic Activities

Most of our gut microbiota live with us in a mutually beneficial life-long relationship. The gut microbiota plays a vital role in the host’s overall health through its metabolic activities. Human microbiota might be supported by consuming friendly bacteria (probiotics) and consuming foods to improve the microbiota (prebiotics). During the last two decades, probiotics’ interest has increased with rising scientific shreds of evidence of benefits on human health. Hence, they have been exploited as various food products, mainly fermented foods. Probiotics as a treatment modality may restore normal microbiota and functioning of the gastrointestinal (GI) tract. Strong scientific evidence is associating these bacteria with the prevention and therapy of various GI disorders. (In light of the ongoing trend of probiotics, further research is needed to obtain the perspective of potential applications for better health. Probiotic applications have been extended from health applications to food and agricultural applications. The benefits of probiotics led to its applications in probiotic ‘health food’ industries and agricultural sectors.

scholarly journals Metabolic activity of gut microbiota and xenobiotics

2015 ◽  
pp. 47-55 ◽  
Author(s):  
Gordana Bojic ◽  
Svetlana Golocorbin-Kohn ◽  
Maja Stojancevic ◽  
Momir Mikov ◽  
Ljiljana Suvajdzic
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Metabolic Activity ◽  
Bacterial Population ◽  
Great Benefit ◽  
Host Organism ◽  
Symbiotic Microorganisms ◽  
Metabolic Activities ◽  
Bacterial Genes

The intestine habitat is the natural collection of symbiotic microorganisms. The bacterial population enables many permanent metabolic activities in this environment. Inside the intestine of mammals there are an extended genome of millions of bacterial genes named microbiome. In recent years, there has been an increased interest of scientists to discover the place and the role of bio-ecological content and modulation of gut microbiota in a host organism using prebiotics, probiotics and synbiotics, which may have a great benefit for human health.

Abstract P485: Association of Hypertension With the Gut Microbiome and Serum Short-chain Fatty Acids

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Moira K Differding ◽  
Lawrence J Appel ◽  
Nisa Maruthur ◽  
Stephen Juraschek ◽  
Edgar R Miller ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Self Report ◽  
Short Chain ◽  
Inverse Association ◽  
Negatively Associated ◽  
Adult Cancer Survivors ◽  
Chain Fatty Acids

Background: Murine models indicate that gut microbiota, and the short chain fatty acids (SCFAs) they produce from fermentation of fiber, play a role in blood pressure (BP) regulation. However, few human studies have examined how gut microbiota and serum SCFAs are associated with hypertension. Objective: We examined associations of gut microbiota composition and serum SCFAs with hypertension and BP, hypothesizing an inverse association with serum SCFAs. Methods: We performed a cross-sectional analysis of baseline data from a trial of overweight and obese adult cancer survivors. We measured 1 ) the gut microbiome by extracting microbial DNA from stool and sequencing the 16S rRNA V4 region and 2 ) serum SCFA using liquid chromatography mass spectrometry. Hypertension was defined as systolic BP ≥ 130, diastolic BP ≥ 80 mmHg, self-report, or use of hypertension medications. We used beta-binomial models to test differential abundance of microbial amplicon sequence variants by hypertension , and linear regression to examine log-transformed SCFAs with BP. We adjusted models for age, sex, race, fiber, BMI and medications (in BP models). Results: Of 111 participants with complete data, 73 had hypertension. Hypertensive participants differed by age (mean 62 vs. 56y) and sex (73% vs. 90% female), but not race (46% black) or BMI (mean 35 kg/m 2 ). Alpha and beta diversity were not associated with hypertension (Ps>0.05). Hypertensive participants had higher abundance of Bacteroides, Parabacteroides, Bifidobacterium and Escherichia , and lower Lachnospiraceae, Haemophilus and Faecalibacterium ( Figure) . Serum acetate was negatively associated with systolic BP (β=-3.3 mmHg difference per 1 SD increment acetate, 95% CI: -6.1, -0.6); other SCFAs were not associated (Ps>0.05). Conclusion: A Bacteroides dominated microbiota was positively associated with hypertension. Acetate, the most abundant circulating SCFA, was negatively associated with BP. Determining whether the associations are causal or not warrants further investigation.

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

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
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.

scholarly journals Gut Microbiome: Profound Implications for Diet and Disease

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1613 ◽  
Author(s):  
Ronald Hills ◽  
Benjamin Pontefract ◽  
Hillary Mishcon ◽  
Cody Black ◽  
Steven Sutton ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Intestinal Bacteria ◽  
Short Chain Fatty Acids ◽  
E Coli ◽  
Beneficial Effects ◽  
Microbial Profile ◽  
Irritable Bowel ◽  
Prebiotic Fiber

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

scholarly journals Muscadine Grape Extract Reduces Lung and Liver Metastasis in Mice with Triple Negative Breast Cancer in Association with Changes in the Gut Microbiome (P05-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh Austin ◽  
Ann Tallant ◽  
Patricia Gallagher
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Triple Negative Breast Cancer ◽  
Gut Microbiome ◽  
Triple Negative ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Muscadine Grape ◽  
Chain Fatty Acids

Abstract Objectives The goal of this study was to determine if a proprietary muscadine grape seed and skin extract (MGE) inhibits triple negative breast cancer (TNBC) metastasis and alters the gut microbiota. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control group (n = 8) or a treatment group that received 0.1 mg/mL total phenolics MGE (Piedmont R&D) in the drinking water (n = 8). Mice were sacrificed after 4 weeks; tissues and fecal samples were collected for analysis. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases using the inForm© 2.2 software. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids were detected by gas chromatography (Microbiome Insights). Data are expressed as means ± SEM using student's t-test. Results MGE reduced Ki67 cell positivity in the lungs and livers of mice, indicating reduced metastatic proliferation (9.3 ± 0.9% vs 6.2 ± 0.7% and 5.0 ± 1.5% vs 0.77 ± 0.2% cells, respectively; P < 0.01), and decreased cancer associated fibroblasts in the lungs (5.3 ± 1.0% vs 3.0 ± 0.5% cells; P < 0.05), which are associated with metastasis. MGE significantly reduced the number (4.7 ± 0.7 vs 2.2 ± 0.4 tumors/field; P < 0.01) and size (1358 ± 48 vs 1121 ± 47 pixels; P < 0.01) of liver metastases, resulting in decreased metastatic tumor burden (6656 ± 1220 vs 3096 ± 644 total area in pixels; P < 0.01). Attenuated TNBC metastasis correlated with MGE-induced changes in gut microbiota. Alpha diversity (4.15 ± 0.10 vs 4.51 ± 0.13 Shannon index; P < 0.05) and the Firmicutes to Bacteroidetes ratio (0.37 ± 0.07 vs 0.76 ± 0.12; P < 0.05) were significantly increased in MGE-treated mice, indicating enhanced microbial richness and increased energy harvest by the gut microbiome. Butyrate-producing bacteria, such as Ruminococcus, Butyricicoccus and Lachnospiraceae, were increased with MGE (P < 0.05) as well as the anti-inflammatory compound butyrate relative to other short-chain fatty acids (25.0 ± 2.7% vs 75.3 ± 15.5%; P < 0.01). Conclusions These data show that MGE attenuates TNBC metastasis in association with alterations in the gut microbiome, suggesting that MGE may be an effective treatment against TNBC metastatic progression. Funding Sources Chronic Disease Research Fund.

scholarly journals The Prebiotic Inulin Beneficially Alters the Gut Microbiome and Associated Metabolites in an APOE4 Mouse Model (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

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