More than just a gut instinct–the potential interplay between a baby's nutrition, its gut microbiome, and the epigenome

Substantial evidence links early postnatal nutrition to the development of obesity later in life. However, the molecular mechanisms of this connection must be further elucidated. Epigenetic mechanisms have been indicated to be involved in this process, referred to as metabolic programming. Therefore, we propose here that early postnatal nutrition (breast and formula feeding) epigenetically programs the developing organs via modulation of the gut microbiome and influences the body weight phenotype including the predisposition to obesity. Specifically, the early-age food patterns are known to determine the gross composition of the early gut microbiota. In turn, the microbiota produces large quantities of epigenetically active metabolites, such as folate and short chain fatty acids (butyrate and acetate). The spectrum of these produced metabolites depends on the composition of the gut microbiota. Hence, it is likely that changes in gut microbiota that result in altered metabolite composition might influence the epigenome of directly adjacent intestinal cells, as well as other major target cell populations, such as hepatocytes and adipocytes. Nuclear receptors and other transcription factors (the PPARs, LXR, RXR, and others) could be physiologically relevant targets of this metabolite-induced epigenetic regulation. Ultimately, transcriptional networks regulating energy balance could be manipulated. For these reasons, we postulate that early nutrition may influence the baby epigenome via microbial metabolites, which contributes to the observed relationship between early nutrition and adult obesity.

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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.

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

npj Parkinson s Disease ◽

10.1038/s41531-021-00156-z ◽

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.

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Adopting seasonal regimen (Ritucharya) to modulate the seasonal variation in gut microbiome

Journal of Ethnic Foods ◽

10.1186/s42779-021-00078-4 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Deepthi. R ◽

Vandana Rani M ◽

Delvin T. Robin ◽

Anusree Dileep

Keyword(s):

Public Health ◽

Gut Microbiota ◽

Gut Microbiome ◽

Health Management ◽

Disease Process ◽

The Body ◽

Leaky Gut ◽

Human Gut ◽

Extrinsic Factors ◽

Application Prospects

AbstractThe science of Ayurveda with its strong and unique fundamentals holds its domain forever amidst all scientific and medical advancements. The concept of Shadkriyakala (the different phases of disease formation) holds relevance in preventive medicine and public health management as it provides ample chance to halt the disease process at each stage by timely intervention. In this review, we would like to bring to the limelight the relevance of Ritucharya (seasonal regimen) in primary prevention by modulating the gut microbiota. The modern gut microbiome researches now help us to better explore the Ayurveda theories of Agni (digestive fire) and Ama (metabolic toxins) preached centuries back. Ayurveda firmly proclaims that no disease ever arises without the derangement of Agni (digestive fire). The whole preventive and treatment methodology in Ayurveda focuses upon the modulation and management of “Agni” (digestive fire). When the functioning of Agni is deranged, Ama (metabolic toxin) is produced and it vitiates the doshas which spread throughout the body and manifest as varied diseases. A biomedical perspective of our reviews suggests that dysbiosis of microbial flora can cause a leaky gut by which the toxins of deranged digestive metabolism enter the bloodstream. Consequently, an inflammatory response occurs within the body which expresses out as diseases opportunistically. We meticulously reviewed the influence of extrinsic factors namely diet and climate on human gut microbiota, and our analysis emphasises the application prospects of Ritucharya (seasonal regimen), in regulating the dynamic host-microbe interaction.

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

Circulation ◽

10.1161/circ.141.suppl_1.p485 ◽

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.

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Gut Microbiome: Profound Implications for Diet and Disease

Nutrients ◽

10.3390/nu11071613 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1613 ◽

Cited By ~ 83

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.

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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)

Current Developments in Nutrition ◽

10.1093/cdn/nzz030.p05-017-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 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.

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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

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Effects of theabrownin on serum metabolites and gut microbiome in rats with a high-sugar diet

Food & Function ◽

10.1039/c9fo01334b ◽

2019 ◽

Vol 10 (11) ◽

pp. 7063-7080 ◽

Cited By ~ 5

Author(s):

Suijuan Yue ◽

Dan Zhao ◽

Chunxiu Peng ◽

Chao Tan ◽

Qiuping Wang ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Gut Microbiome ◽

Strong Correlation ◽

The Body ◽

Serum Metabolites ◽

High Sugar

In a high sugar diet mode, TB reduced the body weight and TG and improved HOMA-IR mainly by targeting the gut microbiota. A strong correlation between cecal microorganisms and serum metabolites, obesity and HOMA-IR was observed.

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Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000403 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Jessica C. Ralston ◽

Kathleen A.J. Mitchelson ◽

Gina M. Lynch ◽

Tam T.T. Tran ◽

Conall R. Strain ◽

...

Keyword(s):

Glucose Tolerance ◽

Gut Microbiota ◽

Glucose Homeostasis ◽

Gut Microbiome ◽

Short Chain Fatty Acids ◽

Microbiota Composition ◽

Wild Type ◽

Low Fat ◽

Unifrac Distance ◽

Gut Microbiota Composition

AbstractReduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

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Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension

Hypertension ◽

10.1161/hypertensionaha.119.13079 ◽

2019 ◽

Vol 74 (6) ◽

pp. 1279-1293 ◽

Cited By ~ 9

Author(s):

Francine Z. Marques ◽

Hamdi A. Jama ◽

Kirill Tsyganov ◽

Paul A. Gill ◽

Dakota Rhys-Jones ◽

...

Keyword(s):

Blood Pressure ◽

Environmental Factors ◽

Gut Microbiota ◽

Environmental History ◽

Gut Microbiome ◽

Blood Pressure Measurement ◽

Short Chain Fatty Acids ◽

Experimental Models ◽

Human Studies ◽

Experimental Hypertension

Hypertension is a complex and modifiable condition in which environmental factors contribute to both onset and progression. Recent evidence has accumulated for roles of diet and the gut microbiome as environmental factors in blood pressure regulation. However, this is complex because gut microbiomes are a unique feature of each individual reflecting that individual’s developmental and environmental history creating caveats for both experimental models and human studies. Here, we describe guidelines for conducting gut microbiome studies in experimental and clinical hypertension. We provide a complete guide for authors on proper design, analyses, and reporting of gut microbiota/microbiome and metabolite studies and checklists that can be used by reviewers and editors to support robust reporting and interpretation. We discuss factors that modulate the gut microbiota in animal (eg, cohort, controls, diet, developmental age, housing, sex, and models used) and human studies (eg, blood pressure measurement and medication, body mass index, demographic characteristics including age, cultural identification, living structure, sex and socioeconomic environment, and exclusion criteria). We also provide best practice advice on sampling, storage of fecal/cecal samples, DNA extraction, sequencing methods (including metagenomics and 16S rRNA), and computational analyses. Finally, we discuss the measurement of short-chain fatty acids, metabolites produced by the gut microbiota, and interpretation of data. These guidelines should support better transparency, reproducibility, and translation of findings in the field of gut microbiota/microbiome in hypertension and cardiovascular disease.

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