Gut microbiome and health: mechanistic insights

Gut, Journal Year: 2022, Volume and Issue: 71(5), P. 1020 - 1032

Published: Feb. 1, 2022

The gut microbiota is now considered as one of the key elements contributing to regulation host health. Virtually all our body sites are colonised by microbes suggesting different types crosstalk with organs. Because development molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), complex interactions occurring between microorganisms progressively being deciphered. Nowadays, deviations linked many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel (IBDs) several cancer. Thus, that various pathways involved in immunity, energy, lipid glucose metabolism affected. In this review, specific attention given provide a critical evaluation current understanding field. Numerous mechanisms explaining how bacteria might be causally protection or onset discussed. We examine well-established metabolites short-chain fatty acids, bile trimethylamine N-oxide) extend more recently identified actors endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products enterosynes) their receptors such peroxisome proliferator-activated receptor alpha (PPARα) gamma (PPARγ), aryl hydrocarbon (AhR), G protein-coupled GPR41, GPR43, GPR119, Takeda 5). Altogether, complexity aspects linking health will help set basis for novel therapies already developed.

Language: Английский

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Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 18, 2022

Abstract The gut microbiome is an important determinant in various diseases. Here we perform a cross-sectional study of Japanese adults and identify the Blautia genus, especially B. wexlerae , as commensal bacterium that inversely correlated with obesity type 2 diabetes mellitus. Oral administration to mice induce metabolic changes anti-inflammatory effects decrease both high-fat diet–induced diabetes. beneficial are unique amino-acid metabolism produce S-adenosylmethionine, acetylcholine, l -ornithine carbohydrate resulting accumulation amylopectin production succinate, lactate, acetate, simultaneous modification bacterial composition. These findings reveal regulatory pathways host microbial may provide novel strategies preventive therapeutic approaches for disorders.

Language: Английский

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gapseq: informed prediction of bacterial metabolic pathways and reconstruction of accurate metabolic models

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: March 10, 2021

Genome-scale metabolic models of microorganisms are powerful frameworks to predict phenotypes from an organism's genotype. While manual reconstructions laborious, automated often fail recapitulate known processes. Here we present gapseq ( https://github.com/jotech/gapseq ), a new tool pathways and automatically reconstruct microbial using curated reaction database novel gap-filling algorithm. On the basis scientific literature experimental data for 14,931 bacterial phenotypes, demonstrate that outperforms state-of-the-art tools in predicting enzyme activity, carbon source utilisation, fermentation products, interactions within communities.

Language: Английский

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Microbiome in Colorectal Cancer: How to Get from Meta-omics to Mechanism?

Trends in Microbiology, Journal Year: 2020, Volume and Issue: 28(5), P. 401 - 423

Published: Feb. 13, 2020

A pathological imbalance of the gut microbiome (dysbiosis) is present in colorectal cancer (CRC) patients.Bacteria may affect CRC directly or indirectly, by secreting metabolites, invading tissues, and modulating host immune response.The underlying pro-oncogenic mechanisms many CRC-associated bacteria remain undescribed.Fusobacterium, Peptostreptococcus, Porphyromonas, Prevotella, Parvimonas, Bacteroides, Gemella are among most prominent bacteria.Many vitro vivo models currently used for studying CRC, such as gut-on-chip models, 3D intestinal organoids, gnotobiotic mouse each offering its own advantage.The microbial metabolism plays an important role CRC. Computational modeling a promising approach genotype-to-metabolic-phenotype relations microbe–microbe host–microbe metabolic interactions. Mounting evidence from metagenomic analyses suggests that state dysbiosis prevalent patients with cancer. Several bacterial taxa have been identified which representative isolate cultures interact human cells trigger disease pathways animal models. However, how complex interrelationships dysbiotic communities be involved pathogenesis remains crucial question. Here, we provide survey current knowledge Moving beyond observational studies, outline new experimental approaches gaining ecosystem-level mechanistic understanding microbiome's pathogenesis. The interplay between gastrointestinal tract (GIT) (see Glossary) has become highly topical area research. represents interface translating agent environmental factors body. Its genomic complement outnumbers unique genes at least 150-fold [1.Qin J. et al.A gene catalogue established sequencing.Nature. 2010; 464: 59-65Crossref PubMed Scopus (5028) Google Scholar]. Primarily, this vast genetic repertoire delivers molecules, support homeostasis health. It aids digestion educates host's system. Furthermore, healthy inhibits proliferation pathogenic their colonization occupying niches competing nutrients. In patients, however, present. therefore suggested interfere molecular Many effects described (Box 1); elusive. Therefore, further efforts required to resolve roles tumor initiation progression. essence, development indirectly affecting associated microenvironment different means: (i) Bacterial secreted complements [e.g., extracellular superoxide, genotoxins, short-chain fatty acids (SCFAs)]; (ii) attachment, invasion, translocation; (iii) defense modulation (e.g., bacteria–immune cell interactions; Figure 1).Box 1Theories on Involvement TumorigenesisTheories behind bacteria-driven tumorigenesis put forth since middle 20th century, when McCoy Mason first link Enterococcus carcinoma sigmoid [157.McCoy W.C. J.M. Enterococcal endocarditis sigmoid; report case.J. Med. Assoc. State Ala. 1951; 21: 162-166PubMed 2011, Sears Pardoll formulated 'alpha-bug' hypothesis, species Bacteroides fragilis exert central pro-oncogenic, enterotoxigenic role, thereby contributing onset [158.Sears C.L. D.M. Perspective: alpha-bugs, partners, colon cancer.J. Infect. Dis. 2011; 203: 306-311Crossref (105) Subsequently, Tjalsma al. proposed driver–passenger model 2012, driver B. fragilis) lead multistep including inflammation, increased cellular proliferation, and/or production genotoxins [159.Tjalsma H. driver-passenger cancer: usual suspects.Nat. Rev. Microbiol. 2012; 10: 575-582Crossref (306) An extension 'Keystone hypothesis' Hajishengallis al., key pathogens, even low abundance, facilitate accessory pathogens [160.Hajishengallis G. al.The keystone-pathogen hypothesis.Nat. 717-725Crossref (561) This followed subversion responses, resulting microbiota pathobionts overstimulate inflammatory response Another theory, applied Helicobacter pylori infections gastric cancers, hit-and-run action tumor-initiating bacteria, whereby toxin CagA leads epigenetic alterations [161.Hatakeyama M. paradigm carcinogenesis.Cell Host Microbe. 2014; 15: 306-316Abstract Full Text PDF (179) potentially transient initiation, but not maintenance, neoplastic phenotype cells. Theories article, overview aforementioned purviews provided covering three main areas identification interactions progression treatment, interaction study Over past few years, culture-based methods quantitative real-time polymerase chain reaction (qRT-PCR) DNA extracted tissue biopsies, well patients' stool, allowed us identify enrichments particular species. addition, present-day next-generation sequencing techniques enabling 16S rRNA profiling fundamental data follow-up studies. comprehensive list sequencing-based (Table 1, Key Table, Supplemental Table S1 online). Although helpful genera, it lacks resolution strain level fails intraspecies diversity, contrast metatranscriptomic approaches. Nevertheless, provides information providing starting point other sensitive approaches, qRT-PCR-based RNA/whole-genome-sequencing-based studies.Table 1Key Table. Top 20 Enriched Genera Species Colorectal Adenoma PatientsaThe ranking was based number studies (referred 'hits'), reporting elevated abundance per bacterium continued online.GenusSpeciesRefsNumber hitsFusobacterium[5.Kostic A.D. al.Genomic analysis identifies association Fusobacterium carcinoma.Genome Res. 22: 292-298Crossref (772) Scholar, 6.Marchesi J.R. al.Towards microbiome.PLoS One. 6e20447Crossref (301) 7.Castellarin al.Fusobacterium nucleatum infection 299-306Crossref (697) 8.Chen W. al.Human lumen mucosa-associated cancer.PLoS 7e39743Crossref (365) 9.Sanapareddy N. al.Increased rectal richness presence adenomas humans.ISME 6: 1858-1868Crossref (101) 10.Wang T. al.Structural segregation volunteers.ISME 320-329Crossref (455) 11.Ahn risk Natl. Cancer Inst. 2013; 105: 1907-1911Crossref (334) 12.McCoy A.N. adenomas.PLoS 8e53653Crossref (230) 13.Warren R.L. al.Co-occurrence anaerobic carcinomas.Microbiome. 1: 16Crossref (164) 14.Tahara colonic flora features carcinoma.Cancer 74: 1311-1318Crossref (181) 15.Zackular J.P. screening tool cancer.Cancer Prev. (Phila.). 7: 1112-1121Crossref (198) 16.Zeller al.Potential fecal early-stage detection cancer.Mol. Syst. Biol. 766Crossref (299) 17.Allali I. al.Gut compositional functional differences non-tumor adjacent tissues cohorts US Spain.Gut Microbes. 2015; 161-172Crossref (13) 18.Burns M.B. al.Virulence signature microenvironment.Genome 55Crossref (71) 19.Feng Q. along adenoma-carcinoma sequence.Nat. Commun. 6528Crossref (273) 20.Gao Z. al.Microbiota disbiosis cancer.Front. 20Crossref (162) 21.Mira-Pascual L. al.Microbial mucosal shifts reveal archaeal biomarkers.J. Gastroenterol. 50: 167-179Crossref 22.Nakatsu across stages carcinogenesis.Nat. 8727Crossref (257) 23.Yu Y.-N. al.Berberine rescue nucleatum-induced microenvironment.Oncotarget. 32013-32026Crossref (39) 24.Yu al.Metagenomic faecal towards targeted non-invasive biomarkers cancer.Gut. 2017; 66: 70-78Crossref (186) 25.Baxter N.T. al.Microbiota-based improves sensitivity immunochemical test detecting lesions.Genome 2016; 8: 37Crossref (76) 26.Flemer al.Tumour-associated non-tumour-associated https://doi.org/10.1136/gutjnl-2015-309595Crossref (176) 27.Vogtmann E. al.Colorectal microbiome: reproducibility whole-genome shotgun sequencing.PLoS 11e0155362Crossref (67) 28.Xu K. Jiang Analysis cancer.Med. Sci. Monit. 23: 4422-4430Crossref (10) 29.Allali Moroccan patients.Med. Immunol. 2018; 207: 211-225Crossref 30.Alomair A.O. al.Colonic single-center Saudi Arabia.Gastroenterol. Pract. 2018: 5284754Crossref (2) 31.Hannigan G.D. al.Diagnostic potential interactive dynamics virome.mBio. 9e02248-18Crossref (24) Scholar]31nucleatum[5.Kostic Scholar,7.Castellarin Scholar,13.Warren Scholar,16.Zeller Scholar,21.Mira-Pascual Scholar,27.Vogtmann Scholar,32.Drewes J.L. al.High-resolution profile meta-analysis biofilm status common consortia.NPJ Biofilms Microbiomes. 3: 34Crossref (50) 33.Dai al.Multi-cohort metagenome altered populations universal markers.Microbiome. 70Crossref (16) 34.Thomas A.M. datasets cross-cohort diagnostic signatures choline degradation.Nat. 2019; 25: 667-678Crossref (44) 35.Yachida S. metabolomic distinct stage-specific phenotypes cancer.Nat. 968-976Crossref (32) Scholar]gonidiaformans[16.Zeller Scholar]mortiferum[34.Thomas Scholar]necrophorum[34.Thomas Scholar]peridonticum[16.Zeller Scholar]Peptostreptococcus[6.Marchesi Scholar,8.Chen Scholar,10.Wang Scholar,11.Ahn Scholar,19.Feng Scholar,20.Gao Scholar,22.Nakatsu Scholar,24.Yu Scholar,28.Xu Scholar,36.Sheng al.Characteristics sites.Oncol. Lett. 18: 4834-4844PubMed Scholar]18stomatis[16.Zeller Scholar,34.Thomas Scholar,35.Yachida Scholar]anaerobius[34.Thomas Scholar]endodontalis[22.Nakatsu Scholar]Porphyromonas[8.Chen Scholar,15.Zackular Scholar,25.Baxter Scholar,37.Geng passenger cancer.Gut Pathog. 26Crossref (23) Scholar]16asaccharolytica[16.Zeller Scholar,33.Dai Scholar]uenonis[34.Thomas Scholar]somerae[34.Thomas Scholar]Bacteroides[8.Chen Scholar,31.Hannigan Scholar,38.Sobhani patients.PLoS 6e16393Crossref (430) Scholar,39.Thomas al.Tissue-associated revealed community profiling.Front. Cell. 179Crossref Scholar]14fragilis[10.Wang Scholar]ovatus[19.Feng Scholar]caccae[19.Feng Scholar]dorei[19.Feng Scholar]eggerthii[19.Feng Scholar]massiliensis[19.Feng Scholar]salyersiae[34.Thomas Scholar]splanchnicus[19.Feng Scholar]vulgatus[19.Feng

Language: Английский

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Advancing human gut microbiota research by considering gut transit time

Gut, Journal Year: 2022, Volume and Issue: 72(1), P. 180 - 191

Published: Sept. 28, 2022

Accumulating evidence indicates that gut transit time is a key factor in shaping the microbiota composition and activity, which are linked to human health. Both population-wide small-scale studies have identified as top covariate contributing large interindividual variation faecal composition. Despite this, still rarely being considered field of microbiome. Here, we review latest research describing how why whole segmental times vary substantially between within individuals, variations impact composition, diversity metabolism. Furthermore, discuss mechanisms by may causally affect motility. We argue taking into account intraindividual differences time, can advance our understanding diet–microbiota interactions disease-related microbiome signatures, since these often be confounded transient or persistent alterations time. Altogether, better complex, bidirectional required understand health disease.

Language: Английский

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Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(700)

Published: June 14, 2023

Alzheimer’s disease (AD) pathology is thought to progress from normal cognition through preclinical and ultimately symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of patients has an altered taxonomic composition compared healthy, cognitively control individuals. However, knowledge about changes in before onset limited. In this cross-sectional study accounted for clinical covariates dietary intake, we microbial function a cohort 164 individuals, 49 whom showed biomarker evidence early AD. Gut profiles individuals were distinct those without The change correlated β-amyloid (Aβ) tau pathological biomarkers but not neurodegeneration, suggesting may process. We identified specific bacterial taxa associated Inclusion these features improved accuracy, sensitivity, specificity machine learning classifiers predicting status when tested on subset (65 participants). correlates neuropathology improve our understanding etiology help identify gut-derived markers risk.

Language: Английский

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Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 238, P. 108176 - 108176

Published: March 26, 2022

Language: Английский

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Orally administered Odoribacter laneus improves glucose control and inflammatory profile in obese mice by depleting circulating succinate

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: Aug. 25, 2022

Abstract Background Succinate is produced by both human cells and gut bacteria couples metabolism to inflammation as an extracellular signaling transducer. Circulating succinate elevated in patients with obesity type 2 diabetes linked numerous complications, yet no studies have specifically addressed the contribution of microbiota systemic or explored consequences reducing intestinal levels this setting. Results Using germ-free microbiota-depleted mouse models, we show that a significant source circulating succinate, which obesity. We also vivo therapeutic treatments selected diminish obese mice. Specifically, demonstrate Odoribacter laneus promising probiotic based on its ability deplete improve glucose tolerance inflammatory profile two independent models ( db/db mice diet-induced mice). Mechanistically, partly mediated receptor 1. Supporting these preclinical findings, inverse correlation between plasma fecal cohort severe associated several components metabolic syndrome including waist circumference, triglycerides, uric acid, among others, primary determinant insulin sensitivity evaluated euglycemic-hyperinsulinemic clamp. Conclusions Overall, our work uncovers O. next-generation obesity-related inflammation.

Language: Английский

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The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases

Gastroenterology, Journal Year: 2023, Volume and Issue: 164(7), P. 1069 - 1085

Published: Feb. 24, 2023

The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have much less well characterized, in part due the expense of untargeted metabolomics and lack ability process data. In this review, we focused on rapidly expanding information about bile acid repertoire produced by microbiome, including impacts acids a wide range host physiological processes diseases, discussed role short-chain fatty other important microbiome-derived metabolites. Of particular note is action metabolites throughout body, which impact ranging from obesity aging disorders traditionally thought as diseases nervous system, that are now recognized being strongly influenced it produces. We also highlighted emerging for modifying improve health or treat disease, "engineered native bacteria'' approach takes bacterial strains patient, modifies them alter metabolism, reintroduces them. Taken together, study derived provided insights into pathophysiological processes, substantial potential new approaches diagnostics therapeutics disease of, involving, gastrointestinal tract.

Language: Английский

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Fish disease and intestinal microbiota: A close and indivisible relationship

Reviews in Aquaculture, Journal Year: 2022, Volume and Issue: 15(2), P. 820 - 839

Published: Nov. 8, 2022

Abstract The gut microbiota is currently one of the most studied ‘organs’ in animals, and fish are no exception. A complex diversity microbes, including bacteria, archaea, yeast fungus, constitute microbiota, creating a interaction with their host accomplishing multiple beneficial functions, such as food digestion, nutrient absorption, immune system, endocrine stress response. microbiota–pathogen protects by mounting colonization resistance, competing for nutrients space. Changes balance community could affect structure homeostasis, inducing dysbiosis. In addition, invading pathogens can induce dysbiosis evading host's defence barriers, acquiring from host, using metabolites produced producing toxins. this regard, understanding interactions within essential to prevent pathogen establishment host. Hence, review describes close indivisible relationships between that lead disease.

Language: Английский

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