Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment

Cell, Год журнала: 2023, Номер 186(9), С. 1846 - 1862.e26

Опубликована: Апрель 1, 2023

Язык: Английский

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Gut microbiota and its metabolites in depression: from pathogenesis to treatment

EBioMedicine, Год журнала: 2023, Номер 90, С. 104527 - 104527

Опубликована: Март 22, 2023

Язык: Английский

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Pathogenesis of autoimmune disease

Nature Reviews Nephrology, Год журнала: 2023, Номер 19(8), С. 509 - 524

Опубликована: Май 10, 2023

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T reactivity to normal constituents the host. These occur widely affect individuals all ages, especially women. Among these diseases, most prominent immunological manifestation is production autoantibodies, which provide valuable biomarkers for diagnosis, classification disease activity. Although cells have key role in pathogenesis, they technically more difficult assay. In general, autoimmune results from an interplay between genetic predisposition environmental factors. Genetic autoimmunity complex can involve multiple genes that regulate function immune populations. Less frequently, result single-gene mutations regulatory pathways. Infection seems be common trigger disease, although microbiota also influence pathogenesis. As shown seminal studies, patients may express autoantibodies many years before appearance clinical or laboratory signs — period called pre-clinical autoimmunity. Monitoring autoantibody expression at-risk populations therefore enable early detection initiation therapy prevent attenuate tissue damage. Autoimmunity not static, however, remission achieved some treated with current agents. host constituents. This Review provides overview basis focus on given their as markers

Язык: Английский

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The gut–liver axis and gut microbiota in health and liver disease

Nature Reviews Microbiology, Год журнала: 2023, Номер 21(11), С. 719 - 733

Опубликована: Июнь 14, 2023

Язык: Английский

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Gut–liver axis: barriers and functional circuits

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2023, Номер 20(7), С. 447 - 461

Опубликована: Апрель 21, 2023

Язык: Английский

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

Mucosal Immunology, Год журнала: 2022, Номер 15(6), С. 1095 - 1113

Опубликована: Сен. 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.

Язык: Английский

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

Gastroenterology, Год журнала: 2023, Номер 166(1), С. 44 - 58

Опубликована: Сен. 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

Язык: Английский

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Emerging roles of intratumor microbiota in cancer metastasis

Trends in Cell Biology, Год журнала: 2022, Номер 33(7), С. 583 - 593

Опубликована: Дек. 14, 2022

Язык: Английский

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Horizontal gene transfer among host-associated microbes

Cell Host & Microbe, Год журнала: 2023, Номер 31(4), С. 513 - 527

Опубликована: Апрель 1, 2023

Язык: Английский

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Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 5, 2023

Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers both pathogens exhibit high disease activity poor clinical outcomes. Colonization PSC-derived Kp specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets sustained suppressive effect vitro. Oral administration the lowers levels Kp-colonized germ-free SPF mice, without off-target dysbiosis. Furthermore, demonstrate oral intravenous successfully suppresses attenuates severity mice. These results collectively suggest using shows promise for targeting PSC.

Язык: Английский

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