The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials

Duan, Hongliang; Wang, Lijuan; Huangfu, Mingmei; Li, Hanyang

doi:10.1016/j.biopha.2023.115276

Cited by 34 publications

(8 citation statements)

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“…In detail, the differentiation of CD4+ T cells into Treg cells can be induced by both propionate and butyrate, producing anti-inflammatory cytokine IL-10 and inhibiting the Th2-skewed and Th17-skewed inflammation. Further, it has been reported that propionate can promote the proliferation of macrophages and dendritic precursor cells, hinder the differentiation of naive T cells into Th2 cells, and thus prevent inflammation (41). Various studies have suggested that Multiple Mendelian randomization (MR) results for three GM taxa causally associated with psoriasis (PSO).…”

Section: Discussionmentioning

confidence: 99%

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study

Zhong,

Wang,

Meng

et al. 2024

Front. Immunol.

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BackgroundAccumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear.ObjectivesTo study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted.MethodsSummary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively.ResultsA total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e−05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e−04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota.ConclusionsIn summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.

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Section: Discussionmentioning

confidence: 99%

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study

Zhong,

Wang,

Meng

et al. 2024

Front. Immunol.

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“…However, butyrate’s precise mechanism in HIF-1α modulation remains unclear, suspected to involve physiological hypoxia. Additionally, butyrate stabilizes HIF-1α via HDAC inhibition, enhancing antimicrobial lysozyme activity ( 211 ). Research has revealed that the butyrate-producing bacterium Faecalibacterium prausnitzii can modulate HIF-1α to enhance IEC IL-18 expression, potentially aiding in mucosal healing in IBD, offering new insights into HIF-1α-mediated SCFA regulation of intestinal mucosal repair and IEB function maintenance ( 212 ).…”

Section: Hif-1α Mediates Scfas Regulation Of Ibdmentioning

confidence: 99%

“…SCFAs reinforce IEB by activating HIF-1α in IEC, heightening tight junction proteins, and curtailing permeability and bacterial translocation ( 93 , 210 ). Their anti-inflammatory action stabilizes HIF-1α via HDAC inhibition, boosting lysozyme activity ( 211 ). SCFAs activate HIF-2α, enhancing goblet cell MUC2 secretion and mucosal defense ( 215 ).…”

Section: Hif-1α Mediates Scfas Regulation Of Ibdmentioning

confidence: 99%

Crosstalk between hypoxia-inducible factor-1α and short-chain fatty acids in inflammatory bowel disease: key clues toward unraveling the mystery

Xiao,

Guo,

Wang

2024

Front. Immunol.

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The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex “residents”, with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1α (HIF-1α), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1α and SCFAs in IBD independently, yet reviews on HIF-1α-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1α in IBD, pivotal for elucidating the disease’s pathogenesis and offering promising therapeutic strategies.

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“…The intestinal flora influences immune cell maturation and function, affecting CD4+ and CD8+ T-cell development and differentiation. Substances produced by the gut microbiota, such as SCFAs, indirectly modulate immune function [ 17 ]: in line with this, acetate, propionate, and butyrate exhibit anti-inflammatory effects by binding to G-protein-coupled receptor 43 (GPR43) in immune cells, limiting histone deacetylase (HDAC) activity, and modulating cytokine and prostaglandin E2 (PGE2) synthesis [ 31 ].…”

Section: Interplay Of Factors In Regulating Skeletal Muscle Physiolog...mentioning

confidence: 99%

Exploring the Gut Microbiota–Muscle Axis in Duchenne Muscular Dystrophy

Mostosi,

Molinaro,

Saccone

et al. 2024

IJMS

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The gut microbiota plays a pivotal role in maintaining the dynamic balance of intestinal epithelial and immune cells, crucial for overall organ homeostasis. Dysfunctions in these intricate relationships can lead to inflammation and contribute to the pathogenesis of various diseases. Recent findings uncovered the existence of a gut–muscle axis, revealing how alterations in the gut microbiota can disrupt regulatory mechanisms in muscular and adipose tissues, triggering immune-mediated inflammation. In the context of Duchenne muscular dystrophy (DMD), alterations in intestinal permeability stand as a potential origin of molecules that could trigger muscle degeneration via various pathways. Metabolites produced by gut bacteria, or fragments of bacteria themselves, may have the ability to migrate from the gut into the bloodstream and ultimately infiltrate distant muscle tissues, exacerbating localized pathologies. These insights highlight alternative pathological pathways in DMD beyond the musculoskeletal system, paving the way for nutraceutical supplementation as a potential adjuvant therapy. Understanding the complex interplay between the gut microbiota, immune system, and muscular health offers new perspectives for therapeutic interventions beyond conventional approaches to efficiently counteract the multifaceted nature of DMD.

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The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials

Cited by 34 publications

References 349 publications

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study

The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study

Crosstalk between hypoxia-inducible factor-1α and short-chain fatty acids in inflammatory bowel disease: key clues toward unraveling the mystery

Exploring the Gut Microbiota–Muscle Axis in Duchenne Muscular Dystrophy

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