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Nature Jan 2014Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and... (Clinical Trial)
Clinical Trial
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Topics: Adult; Bacteria; Bacteroides; Bile Acids and Salts; Bilophila; Carnivory; Diet; Diet, Vegetarian; Dietary Fats; Feces; Female; Fermentation; Food Microbiology; Gastrointestinal Tract; Gene Expression Regulation, Bacterial; Herbivory; Humans; Inflammatory Bowel Diseases; Male; Metagenome; Microbiota; Time Factors; Young Adult
PubMed: 24336217
DOI: 10.1038/nature12820 -
Gut Microbes Jul 2018The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in... (Review)
Review
The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in the maintenance of energy homeostasis and host immunity. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT) by allowing the passage of structural components of bacteria, such as lipopolysaccharides (LPS), which activate inflammatory pathways that may contribute to the development of insulin resistance. Furthermore, intestinal dysbiosis can alter the production of gastrointestinal peptides related to satiety, resulting in an increased food intake. In obese people, this dysbiosis seems be related to increases of the phylum Firmicutes, the genus Clostridium, and the species Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, Akkermansia muciniphila, Clostridium histolyticum, and Staphylococcus aureus.
Topics: Dysbiosis; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Obesity
PubMed: 29667480
DOI: 10.1080/19490976.2018.1465157 -
Frontiers in Immunology 2022Previous researches have implicated a vital association between gut microbiota (GM) and diabetic retinopathy (DR) based on the association of the "gut-retina" axis. But...
BACKGROUND
Previous researches have implicated a vital association between gut microbiota (GM) and diabetic retinopathy (DR) based on the association of the "gut-retina" axis. But their causal relationship has not been elucidated.
METHODS
Instrumental variables of 211 GM taxa were obtained from genome wide association study (GWAS), and Mendelian randomization study was carried out to estimate their effects on DR risk from FinnGen GWAS (14,584 DR cases and 202,082 controls). Inverse variance weighted (IVW) is the main method to analyze causality, and MR results are verified by several sensitive analyses.
RESULTS
As for 211 GM taxa, IVW results confirmed that family- ( = 1.36×10) and family- ( = 3.13×10) were protective factors for DR. Genus- ( = 4.83×10), genus- ( = 3.44×10) and genus- ( = 4.82×10) were correlated with the risk of DR. At the phylum, class and order levels, we found no GM taxa that were causally related to DR (>0.05). Heterogeneity (>0.05) and pleiotropy (>0.05) analysis confirmed the robustness of MR results.
CONCLUSION
We confirmed that there was a potential causal relationship between some GM taxa and DR, which highlights the association of the "gut-retina" axis and offered new insights into the GM-mediated mechanism of DR. Further explorations of their association are required and will lead to find new biomarkers for targeted prevention strategies of DR.
Topics: Diabetes Mellitus; Diabetic Retinopathy; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide
PubMed: 36159877
DOI: 10.3389/fimmu.2022.930318 -
Gut Microbes Nov 2020Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of... (Review)
Review
Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of potentially beneficial microbes to have been recognized are members of the genus , who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of spp. in the gut, have been linked with various human disease states. This review provides an overview of species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.
Topics: Animals; Dysbiosis; Eubacterium; Feces; Gastrointestinal Microbiome; Humans; Phylogeny
PubMed: 32835590
DOI: 10.1080/19490976.2020.1802866 -
Nature Medicine Nov 2022The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut...
The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite-a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.
Topics: Humans; Metabolome; Diet; Gastrointestinal Microbiome; Microbiota; Phenotype; Feces
PubMed: 36216932
DOI: 10.1038/s41591-022-02014-8 -
Cell Host & Microbe Aug 2022Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role...
Microbiota-induced tumorigenesis is well established in solid tumors of the gastrointestinal tract but rarely explored in hematologic malignancies. To determine the role of gut microbiota in lymphoma progression, we performed metagenomic sequencing on human primary gastrointestinal B cell lymphomas. We identified a distinct microbiota profile of intestinal lymphoma, with significantly decreased symbiotic microbes, particularly the genus Eubacterium and notably butyrate-producing Eubacterium rectale. Transfer of E. rectale-deficit microbiota of intestinal lymphoma patients to mice caused inflammation and tumor necrosis factor (TNF) production. Conversely, E. rectale treatment reduced TNF levels and the incidence of lymphoma in sensitized Eμ-Myc mice. Moreover, lipopolysaccharide from the resident microbiota of lymphoma patients and mice synergizes with TNF signaling and reinforces the NF-κB pathway via the MyD88-dependent TLR4 signaling, amalgamating in enhanced intestinal B cell survival and proliferation. These findings reveal a mechanism of inflammation-associated lymphomagenesis and a potential clinical rationale for therapeutic targeting of gut microbiota.
Topics: Animals; Butyrates; Eubacterium; Humans; Inflammation; Mice; Myeloid Differentiation Factor 88; NF-kappa B; Toll-Like Receptor 4
PubMed: 35952646
DOI: 10.1016/j.chom.2022.07.003 -
Gut Apr 2021Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the...
OBJECTIVE
Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
METHODS
In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.
RESULTS
Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as , and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
CONCLUSION
Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
Topics: Adult; Bacteria; C-Reactive Protein; COVID-19; Cytokines; DNA, Bacterial; Dysbiosis; Female; Gastrointestinal Microbiome; Gastrointestinal Tract; Hong Kong; Humans; Immunity; Male; SARS-CoV-2; Severity of Illness Index; Transferases
PubMed: 33431578
DOI: 10.1136/gutjnl-2020-323020 -
Neurobiology of Aging Jan 2017The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what...
The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.
Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Brain; Cognition Disorders; Cytokines; Female; Gastrointestinal Microbiome; Humans; Inflammation; Inflammation Mediators; Intestines; Male; Middle Aged; Plaque, Amyloid
PubMed: 27776263
DOI: 10.1016/j.neurobiolaging.2016.08.019 -
Nutrients Apr 2023The Mediterranean Diet (MD) is plant-based and consists of multiple daily portions of vegetables, fruit, cereals, and olive oil. Although there are challenges with... (Review)
Review
The Mediterranean Diet (MD) is plant-based and consists of multiple daily portions of vegetables, fruit, cereals, and olive oil. Although there are challenges with isolating the MD from the typical Mediterranean lifestyle and culture (including prolonged 'social' meals and siestas), much evidence supports the health benefits of the MD that include improved longevity, reduced metabolic risk of Diabetes Mellitus, obesity, and Metabolic Syndrome, reduced risk of malignancy and cardiovascular disease, and improved cognitive function. The MD is also associated with characteristic modifications to gut microbiota, mediated through its constituent parts (primarily dietary fibres, extra virgin olive oil, and polyunsaturated fatty acids [including ω-3]). These include enhanced growth of species that produce short-chain fatty acids (butyrate), such as and , enhanced growth of , , and species, and reduced growth of Firmicutes and species. Such changes in gut microbiota are known to be associated favourably with inflammatory and oxidative status, propensity for malignancy and overall metabolic health. A key challenge for the future is to explore the extent to which the health benefits of the MD are mediated by such changes to gut microbiota. The MD confers both health and environmental benefits. Adoption of the MD should perhaps be encouraged and facilitated more generally and not just restricted to populations from Mediterranean regions. However, there are key challenges to this approach that include limited perennial availability of the constituent parts of the MD in some non-Mediterranean regions, intolerability of a high-fibre diet for some people, and potential cultural disconnects that juxtapose some traditional (including Western) diets with the MD.
Topics: Humans; Gastrointestinal Microbiome; Diet, Mediterranean; Bacteroides; Bifidobacterium; Butyrates
PubMed: 37432307
DOI: 10.3390/nu15092150 -
Nutrients Jun 2022The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but... (Review)
Review
The involvement of the gut microbiota and the metabolites of colon-residing bacteria in brain disease pathogenesis has been covered in a growing number of studies, but comparative literature is scarce. To fill this gap, we explored the contribution of the microbiota-gut-brain axis to the pathophysiology of seven brain-related diseases (attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, major depressive disorder, and bipolar disorder). In this article, we discussed changes in bacterial abundance and the metabolic implications of these changes on disease development and progression. Our central findings indicate that, mechanistically, all seven diseases are associated with a leaky gut, neuroinflammation, and over-activated microglial cells, to which gut-residing bacteria and their metabolites are important contributors. Patients show a pro-inflammatory shift in their colon microbiota, harbouring more Gram-negative bacteria containing immune-triggering lipopolysaccharides (LPS) in their cell walls. In addition, bacteria with pro-inflammatory properties (, , ) are found in higher abundances, whereas lower abundances of anti-inflammatory bacteria (, , , , , , , , ) are reported, when compared to healthy controls. On the metabolite level, aberrant levels of short-chain fatty acids (SCFAs) are involved in disease pathogenesis and are mostly found in lower quantities. Moreover, bacterial metabolites such as neurotransmitters (acetylcholine, dopamine, noradrenaline, GABA, glutamate, serotonin) or amino acids (phenylalanine, tryptophan) also play an important role. In the future, defined aberrations in the abundance of bacteria strains and altered bacterial metabolite levels could likely be possible markers for disease diagnostics and follow-ups. Moreover, they could help to identify novel treatment options, underlining the necessity for a deeper understanding of the microbiota-gut-brain axis.
Topics: Alzheimer Disease; Autism Spectrum Disorder; Bacteria; Brain; Depressive Disorder, Major; Dysbiosis; Humans
PubMed: 35807841
DOI: 10.3390/nu14132661