Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies

Chemical Reviews, Journal Year: 2022, Volume and Issue: 123(1), P. 31 - 72

Published: Nov. 1, 2022

The human microbiome is composed of a collection dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, coevolution with host has resulted these playing profound role promoting health. Consequently, perturbations can cause or exacerbate several diseases. In this Review, we present our current understanding relationship between health and disease development, focusing on microbiomes found across digestive, respiratory, urinary, reproductive systems as well skin. We further discuss strategies by which composition function be modulated to exert therapeutic effect host. Finally, examine technologies such multiomics approaches cellular reprogramming microbes enable significant advancements research engineering.

Language: Английский

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Rethinking healthy eating in light of the gut microbiome

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(6), P. 764 - 785

Published: June 1, 2022

Language: Английский

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Butyrate’s role in human health and the current progress towards its clinical application to treat gastrointestinal disease

Clinical Nutrition, Journal Year: 2022, Volume and Issue: 42(2), P. 61 - 75

Published: Nov. 2, 2022

Butyrate is a key energy source for colonocytes and produced by the gut microbiota through fermentation of dietary fiber. histone deacetylase inhibitor also signals three G-protein coupled receptors. It clear that butyrate has an important role in gastrointestinal health levels can impact both host microbial functions are intimately with each other. Maintaining optimal improves animal models supporting colonocyte function, decreasing inflammation, maintaining barrier, promoting healthy microbiome. shown protective actions context intestinal diseases such as inflammatory bowel disease, graft-versus-host disease tract, colon cancer, whereas lower and/or microbes which responsible producing this metabolite associated poorer outcomes. However, clinical efforts to increase humans reverse these negative outcomes have generated mixed results. This article discusses our current understanding molecular mechanisms action focus on system, links between factors, currently underway apply knowledge gained from bench bedside.

Language: Английский

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Probiotic‐Inspired Nanomedicine Restores Intestinal Homeostasis in Colitis by Regulating Redox Balance, Immune Responses, and the Gut Microbiome

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(3)

Published: Nov. 7, 2022

Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs). However, the poor clinical outcome so far and limited flexibility of bacterial approach call for improvement. Inspired by health benefits probiotics in alleviating symptoms diseases, bioartificial are designed restore intestinal microenvironment colitis regulating redox balance, immune responses, gut microbiome. The probiotic comprises two components: an E. coli Nissle 1917-derived membrane (EM) as surface biodegradable diselenide-bridged mesoporous silica nanoparticles (SeM) core. When orally administered, probiotic-inspired nanomedicine (SeM@EM) adheres strongly mucus layer restored balance regulation homeostasis a murine model acute induced dextran sodium sulfate. In addition, respective properties EM SeM synergistically alter microbiome favorable state increasing diversity shifting profile anti-inflammatory phenotype. This work suggests safe effective that can IBDs therapy.

Language: Английский

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Microbiome-based interventions to modulate gut ecology and the immune system

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(6), P. 1095 - 1113

Published: Sept. 30, 2022

The gut microbiome lies at the intersection between environment and host, with ability to modify host responses disease-relevant exposures stimuli. This is evident in how enteric microbes interact immune system, e.g., supporting maturation early life, affecting drug efficacy via modulation of responses, or influencing development cell populations their mediators. Many factors modulate ecosystem dynamics during daily life we are just beginning realise therapeutic prophylactic potential microbiome-based interventions. These approaches vary application, goal, mechanisms action. Some entire community, such as nutritional faecal microbiota transplantation, while others, phage therapy, probiotics, prebiotics, target specific taxa strains. In this review, assessed experimental evidence for interventions, a particular focus on clinical relevance, ecological effects, system.

Language: Английский

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Versatility of bacterial outer membrane vesicles in regulating intestinal homeostasis

Science Advances, Journal Year: 2023, Volume and Issue: 9(11)

Published: March 15, 2023

Outer membrane vesicles (OMVs) play vital roles in bacterial communication both intraspecifically and interspecifically. However, extracellular mechanisms of gut microbiota-derived OMVs the intestine remain poorly understood. Here, we report that released from Akkermansia muciniphila are able to (i) restore disturbed balance microbiota by selectively promoting proliferation beneficial bacteria through fusion, (ii) elicit mucosal immunoglobulin A response translocating into Peyer's patches subsequently activating B cells dendritic cells, (iii) maintain integrity intestinal barrier entering epithelial stimulate expressions tight junctions mucus. We demonstrate transplantation microbiota-associated can alleviate colitis enhance anti-programmed cell death protein 1 therapy against colorectal cancer regulating homeostasis. This work discloses importance ecology, providing an alternative target for disease intervention treatment.

Language: Английский

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Reverse metabolomics for the discovery of chemical structures from humans

Nature, Journal Year: 2023, Volume and Issue: 626(7998), P. 419 - 426

Published: Dec. 5, 2023

Abstract Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for public datasets to uncover associations. To demonstrate concept, broadly explored multiple classes metabolites humans, including N -acyl amides, fatty acid esters hydroxy acids, bile conjugated acids. Using repository-scale analysis 1,2 , discovered that some acids associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed cholic Glu, Ile/Leu, Phe, Thr, Trp or Tyr increased Crohn’s disease. Several these related structures affected pathways IBD, such interferon-γ production CD4 + T cells 3 agonism pregnane X receptor 4 . Culture bacteria belonging Bifidobacterium Clostridium Enterococcus genera produced amidates. Because searching repositories has only recently become possible, this approach can now be used general strategy discover other animal ecosystems.

Language: Английский

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Pathobionts in Inflammatory Bowel Disease: Origins, Underlying Mechanisms, and Implications for Clinical Care

Gastroenterology, Journal Year: 2023, Volume and Issue: 166(1), P. 44 - 58

Published: Sept. 20, 2023

The gut microbiota plays a significant role in the pathogenesis of both forms inflammatory bowel disease (IBD), namely, Crohn's (CD) and ulcerative colitis (UC). Although evidence suggests dysbiosis loss beneficial microbial species can exacerbate IBD, many new studies have identified microbes with pathogenic qualities, termed "pathobionts," within intestines patients IBD. concept pathobionts initiating or driving chronicity IBD has largely focused on putative aggravating that adherent invasive Escherichia coli may play CD. However, recent additional bacterial fungal CD UC. This review will highlight characteristics these their implications for treatment. Beyond exploring origins pathobionts, we discuss those associated specific clinical features potential mechanisms involved, such as creeping fat (Clostridium innocuum) impaired wound healing (Debaryomyces hansenii) well increased fecal proteolytic activity (Bacteroides vulgatus) seen biomarker UC severity. Finally, examine impact current therapies, several approaches to target currently early stages development. Despite recognizing likely contribute more work is needed define modes action. Determining whether causal relationships exist between could pave way improved care patients, particularly not responding therapies. incidence diseases (IBD; [CD] [UC]), increasing most industrialized countries.1Ng S.C. Shi H.Y. Hamidi N. et al.Worldwide prevalence 21st century: systematic population-based studies.Lancet. 2017; 390: 2769-2778Abstract Full Text PDF PubMed Scopus (3342) Google Scholar etiology complex, it thought reflect dysregulated immunity develops genetically susceptible individuals after exposure noxious environmental stimuli, including microbes. Genome-wide association than 200 genes2Ye B.D. McGovern D.P.B. Genetic variation IBD: progress, clues possible utility.Expert Rev Clin Microbiol. 12: 1091-1107Google Scholar,3Peters L.A. Perrigoue J. Mortha A. al.A functional genomics predictive network model identifies regulators disease.Nat Genet. 49: 1437-1449Crossref (151) (eg, NOD2, ATG16L1), encoding key proteins underlying host processes aimed at controlling eliminating invading microbes, autophagy, oxidative stress, epithelial barrier integrity, Paneth immune cell functions.4Hampe Franke Rosenstiel P. genome-wide scan nonsynonymous SNPs susceptibility variant Crohn ATG16L1.Nat 2007; 39: 207-211Crossref (1596) Scholar,5Hugot Chamaillard M. Zouali H. al.Association NOD2 leucine-rich repeat variants disease.Nature. 2001; 411: 599-603Crossref (4813) Only 19%–26% heritability explained by genetics,3Peters suggesting factors, bacteria, promote even without genetic susceptibility. Interestingly, prior acute infection enteric pathogens related antibiotic exposures been repeatedly shown be risk factors IBD.6Faye A.S. Allin K.H. Iversen A.T. al.Antibiotic use factor across ages: cohort study.Gut. 2023; 72: 663-670Crossref (16) they are unlikely directly because typically precede development years. Intestinal well-established feature IBD.7Gevers D. Kugathasan S. Knights Microbiome Foundation Study Disease.Cell Host Microbe. 21: 301-304Abstract (37) Scholar,8Michail Durbin Turner al.Alterations microbiome children severe colitis.Inflamm Bowel Dis. 2013; 18: 1799-1808Google Previously defined "compositional alterations [driven by] host-related factors,"9Levy Kolodziejczyk A.A. Thaiss C.A. al.Dysbiosis system.Nat Immunol. 17: 219-232Crossref (947) caused inflammation, infection, genetics, dietary habits characterized one following: blooms potentially an overall diversity.9Levy Scholar,10Tiffany C.R. Bäumler A.J. Dysbiosis: from fiction function.Am J Physiol - Gastrointest Liver Physiol. 2019; 317: G602-G608Crossref (0) often found bidirectional nature intestinal inflammation concurrent only recently investigated. Historically, recruited analysis relative healthy controls, displaying reduced diversity temporal compositional variability.11Matsuoka K. Kanai T. disease.Semin Immunopathol. 2015; 37: 47-55Crossref (532) Scholar, 12Kostic A.D. Xavier R.J. Gevers disease: status future ahead.Gastroenterology. 2014; 146: 1489-1499Abstract (1235) 13Ryan F.J. Ahern A.M. Fitzgerald R.S. al.Colonic epigenomic Commun. 2020; 11: 1-12Crossref (147) 14Clooney A.G. Eckenberger Laserna-Mendieta E. al.Ranking variance large longitudinal intercontinental 2021; 70: 499-510Crossref (109) To further clarify dysbiotic compared present paired inflamed noninflamed tissues Most differences taxa sites Enterobacteriaceae Bacteroides decreased Firmicutes), however, varied same study.13Ryan Scholar,15Hirano Umeno Okamoto Y. al.Comparison community structure non-inflamed colitis.J Gastroenterol Hepatol. 2018; 33: 1590-1597Crossref (77) 16Moen A.E.F. Lindstrøm J.C. Tannæs T.M. al.The transcriptional mucosal patients.Sci Rep. 8: 1-12Google 17Walker A.W. Sanderson J.D. Churcher C. al.High-throughput clone library mucosa-associated reveals regions intestine disease.BMC 2011; (561) limitations past include relatively shallow sequencing depth rarely surpasses genus level, small sizes, notwithstanding inherent complexity studying microbiota,9Levy consideration composition, functionality, member interactions, factors. limitations, noted findings indicate composition patient specific, no single suspect UC, supporting notion diverse members progression. evident co-occur merely byproduct difficult investigate. Prospective notoriously challenging conduct. study used samples first-degree relatives collected Colitis Canada's Environmental Microbial project identify CD.18Raygoza Garay J.A. Turpin W. Lee S.-H. al.Gut onset Disease relatives.Gastroenterology. 165: 670-681Abstract (12) Using machine learning, Risk Score was generated 70 who developed (of 3483 total participants), which Ruminococcus torques Blautia (both mucin-degraders), Colidextribacter, Oscillospiraceae, Roseburia predictors onset.18Raygoza In addition, changes, activity, were previously later UC.19Galipeau H.J. Caminero al.Novel biomarkers diagnosis colitis.Gastroenterology. 160: 1532-1545Abstract (86) These pioneering provide stepping stone trace changes before at-risk groups throughout natural progression disease. Such information help transition Many animal demonstrated drive dysbiosis, also inflammation.20Singh V.P. Proctor S.D. Willing B.P. Koch's postulates, disease.Clin Microbiol Infect. 2016; 22: 594-599Abstract (33) 21Glymenaki Singh G. Brass al.Compositional mucus colitis-induced inflammation.Inflamm 23: 912-922Crossref (41) 22Ni Wu G.D. Albenberg L. causation correlation?.Nat 14: 573-584Crossref (971) should exercise caution when extrapolating rodent models applying human disease,23Walter Armet Finlay B.B. al.Establishing exaggerating causality microbiome: lessons microbiota-associated rodents.Cell. 180: 221-232Abstract (271) this positive feedback loop unfortunate "recipe" Even so, reflects array intertwined bacterial-host differs based status, baseline microbiota. One popular hypothesis progression, facilitated concomitant commensals24Cococcioni Panelli Varotto-boccazzi I. al.IBDs pediatric age: peculiarities involvement microbiota.Dig 53: 17-25Scopus (7) metabolites, short-chain fatty acid butyrate.25Byndloss M.X. Olsan E.E. Rivera-Chávez F. al.Microbiota-activated PPAR-g signaling inhibits expansion.Science. 575: 570-575Google Reduced butyrate levels shift colonocyte metabolism phosphorylation glycolysis, elevating luminal oxygen accelerating strict anaerobes.25Byndloss Correspondingly, know facultative anaerobic commensals, coli, survive oxygen-rich environment, assume vacated niches, acquire nutrients, expand numbers.25Byndloss Scholar,26Baldelli V. Scaldaferri Putignani enterobacteriaceae diseases.Microorganisms. 9: 1-15Google Along commensal E there other possessing known "pathobionts" hypothesized either initiation, aggravation IBD.27Chow Tang Mazmanian S.K. Pathobionts gastrointestinal disease.Curr Opin 473-480Crossref (309) term "pathobiont" first introduced 2008 Helicobacter hepaticus, where bacterium potential.28Mazmanian Round J.L. Kasper D.L. A symbiosis prevents 2008; 453: 620-625Crossref (1814) initial definition describe function,29Stecher B. Maier Hardt W.D. "Blooming" gut: how might pathogen evolution.Nat 277-284Crossref (262) 30Ha C.W.Y. Martin Sepich-Poore al.Translocation viable mesenteric adipose drives formation humans.Cell. 183: 666-683Abstract (174) 31Mottawea Chiang C.K. Mühlbauer al.Altered microbiota-host mitochondria crosstalk 713419Google 32Yang Nguyen Khetrapal al.Within-host evolution pathobiont facilitates liver translocation.Nature. 2022; 607: 563-570Crossref (45) "IBD pathobionts" micro-organisms able cause via niche-seeking tendencies. best-characterized adherent-invasive (AIEC). First isolated 1998,33Darfeuille-Michaud Neut Barnich al.Presence strains ileal mucosa disease.Gastroenterology. 1998; 115: 1405-1413Abstract (687) CD, bacteria functions (such invasion) rather markers, meaning express toxins virulence AIEC strain LF82 uses its adhesin FimH adhere cells (IEC) expressing carcinoembryonic antigen-related adhesion molecule 6 receptor.34Dreux Denizot Martinez-Medina al.Point mutations disease-associated enhance response.PLoS Pathog. e1003141Crossref (123) Scholar,35Barnich Carvalho F.A. Glasser A.L. al.CEACAM6 acts receptor colonization disease.J Invest. 117: 1566-1574Crossref (449) Because expression up-regulated explain AIEC's preferential adherence inflammation. Moreover, inside cells, macrophages, triggering release proinflammatory cytokines.36Glasser Boudeau al.Adherent replicate macrophages inducing death.Infect Immun. 69: 5529-5537Crossref (346) Recently invasion, strains, correlate potentiation mice, indeed inflammation.37Kittana Gomes-neto Heck al.Evidence (AIEC) inflammation.mSphere. 8 (e00478-22)Google Recent success blocking identifying targeting prove effective treating symptoms future.38Chevalier Laveissière Desachy al.Blockage disease.Microbiome. 1-16Google instrumental advancing our understanding already described previous articles.39Darfeuille-Michaud Adherent-invasive coli: s pathotype disease.Int Med 2002; 292: 185-193Crossref 40Rolhion Darfeuille-Michaud disease.Inflamm 13: 1277-1283Crossref (210) 41Martinez-Medina Garcia-Gil L.J. chronic diseases: update pathogenicity.World Pathophysiol. 5: 213Crossref 42Palmela Chevarin Xu Z. al.Adherent-invasive disease.Gut. 67: 574-587Crossref (316) 43Mansour Asrar Elhenawy multifaceted coli.Gut Microbes. 152172669Google Instead, focus pathogenesis. Under states perturbation, alter host's state seeking out producing surface structures thus exacerbating By addressing pathologies, underscore playing active development, severity, actions underlie cases failed treatment response frequent relapse. prominent source pathobionts. They individuals44Bücker R. Schulz Günzel al.α-Haemolysin potentiator colon.Gut. 63: 1893-1901Crossref (52) 45Bhattacharjee Flores Woelfel-Monsivais al.Diversity Clostridium innocuum microbiota.mSphere. 46Nadalian Yadegar Houri al.Prevalence meta-analysis.J 36: 852-863Crossref (35) reside causing detectable disease, environment largest determining When becomes perturbed,9Levy disrupted balance commensals support expansion production harmful metabolic byproducts, Inflammation perturbation underlies emergence expansion, similar blooms.9Levy precedes during onset,18Raygoza effects requires investigation. With being arguably important contributing must heritable,47Turpin Goethel Bedrani al.Determinants heritability: genes, bugs, more.Inflamm 24: 1133-1148Crossref (103) factors48Turpin Espin-Garcia O. genome cohort.Nat 48: 1413-1417Crossref (311) through vertical transmission.49Torres Hu Seki al.Infants born mothers altered transfers abnormalities adaptive system germ-free mice.Gut. 42-51Crossref (111) Scholar,50Kim E.S. Tarassishin Eisele al.Longitudinal calprotectin among pregnant women babies.Gastroenterology. 1118-1130.e3Abstract (38) infant strongly influenced maternal microbiome49Torres Scholar,51Wang Ryan Boyaval al.Maternal transmission affecting early-life development.Trends 28: 28-45Abstract (97) diagnosed younger ages, while suffering ever before,24Cococcioni Scholar,52Day Lemberg D.A. Identification colitisin children.J Paediatr Child Health. 56: 1731-1734Google acquisition familial peri-natal 2019 had lower detected infant's stool.49Torres assessing consequences, sourced stool, imbalance systems recipient mice. Cells colonic lamina propria showed reduction class-switched memory B immunoglobulin (Ig) A+ regulatory T (mother's stool only).49Torres Also transmission, elevated infants low experienced life correlation composition.50Kim Extending concepts mouse dam neonate resulted adult mice colonized AIEC.53Brand M.W. Hostetter J.M. al.Vertical attaching . neonatal predisposes following colitic insult life.PLoS One. 17e0266005Google Currently, ongoing trial investigating utero mother newborn determine subsequent (ClinicalTrials.gov Identifier: NCT03116568). heritable, large, carefully controlled humans required if acquired infants, promoting Parental transfer families; therefore, discussions approached until validated interventions available. Another oral microbiome, increasingly recognized contributor pathogenesis, patients.54Schirmer Denson Vlamakis linked course.Cell 2

Language: Английский

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Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 141, P. 103062 - 103062

Published: May 27, 2023

Language: Английский

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Scientific novelty beyond the experiment

Microbial Biotechnology, Journal Year: 2023, Volume and Issue: 16(6), P. 1131 - 1173

Published: Feb. 14, 2023

Practical experiments drive important scientific discoveries in biology, but theory-based research studies also contribute novel-sometimes paradigm-changing-findings. Here, we appraise the roles of approaches focusing on experiment-dominated wet-biology areas microbial growth and survival, cell physiology, host-pathogen interactions, competitive or symbiotic interactions. Additional examples relate to analyses genome-sequence data, climate change planetary health, habitability, astrobiology. We assess importance thought at each step process; natural philosophy, inconsistencies logic language, as drivers progress; value experiments; use limitations artificial intelligence technologies, including their potential for interdisciplinary transdisciplinary research; other instances when theory is most-direct most-scientifically robust route novelty development techniques practical experimentation fieldwork. highlight intrinsic need human engagement innovation, an issue pertinent ongoing controversy over papers authored using/authored by (such large language model/chatbot ChatGPT). Other issues discussed are way which aspects can bias thinking towards spatial rather than temporal (and how this biased lead skewed terminology); receptivity that non-mainstream; science education epistemology. Whereas briefly classic works (those Oakes Ames, Francis H.C. Crick James D. Watson, Charles R. Darwin, Albert Einstein, E. Lovelock, Lynn Margulis, Gilbert Ryle, Erwin R.J.A. Schrödinger, Alan M. Turing, others), focus microbiology more-recent, discussing these context process types they represent. These include several carried out during 2020 2022 lockdowns COVID-19 pandemic access laboratories was disallowed (or limited). interviewed authors some featured microbiology-related and-although ourselves involved laboratory fieldwork-also drew from our own experiences showing such not only produce new findings transcend barriers between disciplines, act counter reductionism, integrate biological data across different timescales levels complexity, circumvent constraints imposed techniques. In relation urgent needs, believe global challenges may require beyond experiment.

Language: Английский

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