Metabolic Host–Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD)

Dowdell, Alexander S.; Colgan, Sean P.

doi:10.3390/ph14080708

Cited by 25 publications

(12 citation statements)

References 203 publications

(210 reference statements)

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“…Taken together, IPA produced only by the gut microbiota plays a direct or indirect role in various disease models that have not been previously recognized. Strikingly, IPA is well tolerated in current mouse models with no adverse effects [ 77 , 134 ]. However, there remain many problems and challenges in the clinical application of IPA, which need to be further explored in follow-up research.…”

Section: Discussionmentioning

confidence: 99%

“…It is gratifying that the positive role of IPA in neurological diseases is becoming increasingly recognized by researchers. Indeed, IPA has been used in the clinical development of the neurological disorder, Friedrich’s ataxia [ 77 ]. Thus, IPA has become a research hotspot in the research and clinical usage of the gut–brain axis.…”

Section: The Roles Of Ipa In Host Diseases and Healthmentioning

confidence: 99%

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Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

2022

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Increasing evidence suggests that metabolites produced by the gut microbiota play a crucial role in host–microbe interactions. Dietary tryptophan ingested by the host enters the gut, where indole-like metabolites such as indole propionic acid (IPA) are produced under deamination by commensal bacteria. Here, we summarize the IPA-producing bacteria, dietary patterns on IPA content, and functional roles of IPA in various diseases. IPA can not only stimulate the expression of tight junction (TJ) proteins to enhance gut barrier function and inhibit the penetration of toxic factors, but also modulate the immune system to exert anti-inflammatory and antioxidant effects to synergistically regulate body physiology. Moreover, IPA can act on target organs through blood circulation to form the gut–organ axis, which helps maintain systemic homeostasis. IPA shows great potential for the diagnosis and treatment of various clinical diseases, such as NAFLD, Alzheimer’s disease, and breast cancer. However, the therapeutic effect of IPA depends on dose, target organ, or time. In future studies, further work should be performed to explore the effects and mechanisms of IPA on host health and disease to further improve the existing treatment program.

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Section: Discussionmentioning

confidence: 99%

Section: The Roles Of Ipa In Host Diseases and Healthmentioning

confidence: 99%

Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

2022

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“…Changes in the intestinal barrier can cause bacteria to migrate into the intestinal mucosa or portal vein circulation, which alters the host-microbe interactions that are key to intestinal inflammation[ 36 ]. In particular, gut cells can sense microbe-derived, pathogen-associated molecular patterns through pattern recognition receptors[ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

Ji¹,

Dai²,

Wen³

et al. 2022

WJCC

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BACKGROUND Inflammatory bowel disease (IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine (TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmeric-trisomes on inducing mucosal healing in IBD is not clear. AIM To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques. METHODS The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A “zedoary turmeric-trisomes-chemical composition-target-disease” network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the “Network Analysis” plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the “zedoary turmeric-trisomes-chemical composition-target-disease” network was performed using Sybyl-x 2.1.1 software. RESULTS A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity. CONCLUSION This study identified the potential m...

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“…Disturbances in the composition of the gut microbiota can impact the integrity of the gut barrier and are linked with the development of (chronic) inflammatory and metabolic diseases [5][6][7]. Furthermore, the proinflammatory state associated with aging, often referred to as inflammaging, has been associated with changes in the gut microbiome [8][9][10]. Recently, we showed that high abundance of the gut commensals Ruminococcus torques and Escherichia coli, often observed in inflammatory processes such as inflammatory bowel disease [11][12][13], were associated with a pro-inflammatory immune profile in the ageing population with influenza-like illness (ILI) [14].…”

Section: Introductionmentioning

confidence: 99%

Ecological interactions between host, commensal and pathogenic bacteria in models for the intestinal epithelium

Nanlohy,

Johannesson,

Wijnands

et al. 2023

Preprint

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Gut host physiology and the microbiome intricately interact in the complex ecosystem of the human digestive tract, playing a crucial role in maintaining overall health. In recent decades, the role of the gut microbiota in the defence against pathogens and modulating local and distal immunity has been well-established. The interactions between commensal and potential pathogenic bacteria with the intestinal epithelium can initiate immune responses in the epithelial cells, which, in turn, activate downstream immune responses in other immune cells. These intricate processes involved, especially when multiple microorganisms are present as seen in the intestinal microbiome, remain only partially understood. Previously, it was observed that in adults aged 60 years or older, the commensalRuminococcus torques(Rt) andEscherichia coliwere associated with influenza-like illness and a heightened pro-inflammatory immune profile. In this study, we used a CaCo-2 cell-based model and a human intestinal enteroid (HIE) model to explore epithelial responses to Rt and an adherent invasiveE. coli(AIEC) both individually and in co-cultures under anaerobic conditions. Additionally, CaCo-2 cells were co-cultured with peripheral blood mononuclear cells, revealing downstream activation of immune cells. While both systems showed comparable cytokine profiles, they differed in their responses to the different bacteria, with the organoid system being more representative for intestinal epithelial cells in humans. We provide mechanistic evidence of the pro-inflammatory responses associated with these bacteria in the intestinal ecosystem. These models, particularly in the context of combined infections, represent a valuable and promising avenue for future research. They contribute to a deeper understanding of the complex interactions between the gut microbiota, epithelial intestinal cells and immune cells in the gut ecosystem, thereby promoting advances in the field of gut health and host response.

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Metabolic Host–Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD)

Cited by 25 publications

References 203 publications

Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

Ecological interactions between host, commensal and pathogenic bacteria in models for the intestinal epithelium

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