A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2 DOI Creative Commons
Werner C. Albrich, Tarini Shankar Ghosh, Sinead Ahearn‐Ford

et al.

Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)

Published: May 15, 2022

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic immune responses that limit viral spread promote recovery of damaged systems. However, the role gut microbiota in regulating these has not been thoroughly investigated. In order to identify mechanisms underpinning interactions with host systems influence disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients compared those most outcome (i.e. death, n = 41) non-fatal (n 89), or mild/moderate 42), recovered. A distinct subset 8 cytokines (e.g. TSLP) 140 metabolites quinolinate) sera identified fatal infection. addition, elevated levels multiple pathobionts lower protective anti-inflammatory microbes were observed fecal microbiome poorest outcomes. Weighted gene correlation network (WGCNA) modules severity-associated tryptophan metabolism, coagulation-linked fibrinopeptides, bile acids pathobionts, such as Enterococcus. contrast, less outcomes are clusters Bifidobacterium Ruminococcus, short chain fatty (SCFAs) IL-17A. Our study uncovered mechanistic link processes SARS-CoV-2 These features may be useful at risk individuals, but also highlight for modifying hyperinflammatory other infectious agents.

Language: Английский

Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis DOI Creative Commons
Juanjuan Wang, Ningning Zhu, Lei Su

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 793 - 793

Published: March 2, 2023

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to regulation of host immune response homeostasis. Alterations have been found in many immune-related diseases. metabolites generated by specific microorganisms such as short-chain fatty acids (SCFAs), tryptophan (Trp) bile acid (BA) metabolites, not only affect genetic epigenetic but also impact metabolism cells, immunosuppressive inflammatory cells. cells (such tolerogenic macrophages (tMacs), dendritic (tDCs), myeloid-derived suppressive (MDSCs), regulatory T (Tregs), B (Breg) innate lymphocytes (ILCs)) Macs (iMacs), DCs, CD4 helper (Th)1, CD4Th2, Th17, natural killer (NK) NK neutrophils) express different receptors for SCFAs, Trp BA from microorganisms. Activation these promotes differentiation function inhibits causing reprogramming local systemic system maintain homeostasis individuals. We here will summarize recent advances understanding effects on homeostasis, especially functions

Language: Английский

Citations

199
Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis DOI Creative Commons
Lei Su,

Yunhuan Gao,

Rongcun Yang

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2296 - 2296

Published: July 25, 2022

Tryptophan is an essential amino acid from dietary proteins. It can be metabolized into different metabolites in both the gut microbiota and tissue cells. such as indole-3-lactate (ILA), indole-3-acrylate (IAC), indole-3-propionate (IPA), indole-3-aldehyde (IAID), indoleacetic (IAA), indole-3-acetaldehyde Kyn produced by intestinal microorganisms through direct Trp transformation also, partly, kynurenine (Kyn) pathway. These play a critical role maintaining homeostasis of systematic immunity also potentially affect occurrence development diseases inflammatory bowel diseases, tumors, obesity metabolic syndrome, nervous system, infectious vascular inflammation cardiovascular hepatic fibrosis. They not only promote differentiation function anti-inflammatory macrophages, Treg cells, CD4

Language: Английский

Citations

193
New Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases DOI

Xiaojing Li,

Binbin Zhang, Yiyang Hu

et al.

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 13, 2021

The interaction between host and microorganism widely affects the immune metabolic status. Indole its derivatives are metabolites produced by metabolism of tryptophan catalyzed intestinal microorganisms. By activating nuclear receptors, regulating hormones, affecting biological effects bacteria as signaling molecules, indole maintain homeostasis impact liver response, which shows good therapeutic prospects. We reviewed recent studies on derivatives, including related metabolism, influence diets commensal bacteria, targets mechanisms in pathological conditions, especially progress strategies. New research insights into indoles will facilitate a better understanding their druggability application diseases.

Language: Английский

Citations

141
Dual Role of Indoles Derived From Intestinal Microbiota on Human Health DOI Creative Commons
Xuewei Ye, Haiyi Li, Komal Anjum

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 17, 2022

Endogenous indole and its derivatives (indoles), considered as promising N-substituted heterocyclic compounds, are tryptophan metabolites derived from intestinal microbiota exhibit a range of biological activities. Recent studies indicate that indoles contribute to maintaining the barrier human intestine, which exert anti-inflammatory activities mainly through activating AhR PXR receptors affect immune system’s function, significantly improving health (inflammatory bowel disease, hemorrhagic colitis, colorectal cancer) further promote (diabetes mellitus, central system inflammation, vascular regulation). However, revealed toxic influences cannot be ignored. Indoxyl sulfate, an derivative, performs nephrotoxicity cardiovascular toxicity. We addressed interaction between indoles’ effects on double-edged swords. This review provides scientific bases for correlation with diseases moreover highlights several directions subsequent indoles-related studies.

Language: Английский

Citations

125
Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid DOI Creative Commons
Wenchao Wei, Chi Chun Wong, Zhongjun Jia

et al.

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(8), P. 1534 - 1548

Published: June 29, 2023

Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and characterized by inflammation fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via gut microbiota. Here, we investigated mechanistic role microbiota ameliorating NASH dietary fibre mice. Soluble inulin was found be more effective than insoluble cellulose suppress progression mice, reduced hepatic steatosis, necro-inflammation, ballooning fibrosis. We employed stable isotope probing trace incorporation 13C-inulin into bacterial genomes metabolites during progression. Shotgun metagenome sequencing revealed that commensal Parabacteroides distasonis enriched 13C-inulin. Integration metagenomes metabolomes suggested P. used produce pentadecanoic acid, an odd-chain which confirmed vitro germ-free or acid protective against Mechanistically, inulin, restored barrier function models, serum lipopolysaccharide pro-inflammatory cytokine expression. Overall shows members can use generate beneficial disease.

Language: Английский

Citations

101
Small Intestinal Bacterial Overgrowth—Pathophysiology and Its Implications for Definition and Management DOI Open Access
Daniel Bushyhead, Eamonn M.M. Quigley

Gastroenterology, Journal Year: 2022, Volume and Issue: 163(3), P. 593 - 607

Published: April 7, 2022

Language: Английский

Citations

80
IBD disease-modifying therapies: insights from emerging therapeutics DOI
Niranjan G. Kotla, Yury Rochev

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 241 - 253

Published: Jan. 30, 2023

Language: Английский

Citations

64
Immunomodulatory effects of inulin and its intestinal metabolites DOI Creative Commons

Wei Sheng,

Guang Ji, Li Zhang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 10, 2023

“Dietary fiber” (DF) refers to a type of carbohydrate that cannot be digested fully. DF is not an essential nutrient, but it plays important part in enhancing digestive capacity and maintaining intestinal health. Therefore, supplementation the daily diet highly recommended. Inulin soluble DF, commonly added foods. Recently, several studies have found dietary inulin can improve metabolic function regulate immunity. fermented colon by gut microbiota series metabolites generated. Among these metabolites, short-chain fatty acids provide energy epithelial cells participate regulating differentiation immune cells. its contribute host This review summarizes effect on immunity, underlying mechanisms preventing diseases such as 2 diabetes mellitus, inflammatory bowel disease, chronic kidney certain cancer types.

Language: Английский

Citations

54
Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating AHR/NRF2/NLRP3 Inflammasome Pathways through Indole-3-lactic Acid Production DOI

Qingyu Cui,

Zhe Zhang, Xiaoying Tian

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(4), P. 1970 - 1981

Published: Jan. 12, 2023

In this study, the effectors and mechanisms of Bifidobacterium bifidum FL-276.1 B. FL-228.1 in alleviating dextran sulfate sodium (DSS)-induced colitis were investigated. Both significantly alleviated DSS-induced colitis, whether they supplemented from beginning experiment (whole course intervention) or after DSS induction started (partial intervention). Aryl hydrocarbon receptor (AHR) nuclear factor erythroid 2-related 2 (NRF2) pathways activated mice colons, while NLR family pyrin domain containing 3 (NLRP3) was downregulated under whole intervention modes. Indole-3-lactic acid, an AHR ligand produced by FL-228.1, could regulate AHR/NRF2/NLRP3 pathway Caco-2 monolayers, thus upregulating tight junction proteins protecting integrity epithelial barrier. These results are conducive to promoting clinical trials product development probiotics for colitis.

Language: Английский

Citations

48
The diagnostic and prognostic potential of gut bacteria in inflammatory bowel disease DOI Creative Commons
Dickson Kofi Wiredu Ocansey,

Sanhua Hang,

Xinyi Yuan

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: Feb. 16, 2023

The gut microbiome serves as a signaling hub that integrates environmental inputs with genetic and immune signals to influence the host's metabolism immunity. Gut bacteria are intricately connected human health disease state, specific species driving characteristic dysbiosis found in gastrointestinal conditions such inflammatory bowel (IBD); thus, changes could be harnessed improve IBD diagnosis, prognosis, treatment. advancement next-generation sequencing techniques 16S rRNA whole-genome shotgun has allowed exploration of complexity microbial ecosystem high resolution. Current data is promising appears perform better some studies than currently used fecal inflammation biomarker, calprotectin, predicting from healthy controls irritable syndrome (IBS). This study reviews current on differential potential within cohorts, between other diseases.

Language: Английский

Citations

43