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Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity.

ABSTRACT: The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging. This chronic inflammatory state, also known as inflammaging, induced by the chronic activation of the innate immune system via the macrophage, is controlled by the gut microbiota, which links nutrition, metabolism, and the innate immune response. Here, we present the functional roles of prebiotics, probiotics, synbiotics, and postbiotics as bioactive compounds by underscoring their putative contributions to (1) the reduction in gut hyperpermeability due to lipopolysaccharide (LPS) inactivation, (2) increased intestinal barrier function as a consequence of the upregulation of tight junction proteins, and (3) inhibition of proinflammatory pathways, overall leading to the alleviation of chronic inflammation in the management of obesity.

SUBMITTER: Apalowo OE

PROVIDER: S-EPMC10969769 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity.

Apalowo Oladayo Emmanuel OE Adegoye Grace Adeola GA Obuotor Tolulope Mobolaji TM

Current issues in molecular biology 20240228 3

The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive divers ...[more]

PMID: 38534735

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Project description:BackgroundThe host-microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, and microbial tryptophan metabolites are potent modulators of host physiology. However, whether and how these metabolites mediate host-microbiota interactions, particularly in terms of inter-microbial communication, remains unclear.ResultsHere, we have demonstrated that indole-3-lactic acid (ILA) is a key molecule produced by Lactobacillus in protecting against intestinal inflammation and correcting microbial dysbiosis. Specifically, Lactobacillus metabolizes tryptophan into ILA, thereby augmenting the expression of key bacterial enzymes implicated in tryptophan metabolism, leading to the synthesis of other indole derivatives including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Notably, ILA, IPA, and IAA possess the ability to mitigate intestinal inflammation and modulate the gut microbiota in both DSS-induced and IL-10-/- spontaneous colitis models. ILA increases the abundance of tryptophan-metabolizing bacteria (e.g., Clostridium), as well as the mRNA expression of acyl-CoA dehydrogenase and indolelactate dehydrogenase in vivo and in vitro, resulting in an augmented production of IPA and IAA. Furthermore, a mutant strain of Lactobacillus fails to protect against inflammation and producing other derivatives. ILA-mediated microbial cross-feeding was microbiota-dependent and specifically enhanced indole derivatives production under conditions of dysbiosis induced by Citrobacter rodentium or DSS, but not of microbiota disruption with antibiotics.ConclusionTaken together, we highlight mechanisms by which microbiome-host crosstalk cooperatively control intestinal homoeostasis through microbiota-derived indoles mediating the inter-microbial communication. These findings may contribute to the development of microbiota-derived metabolites or targeted "postbiotic" as potential interventions for the treatment or prevention of dysbiosis-driven diseases. Video Abstract.

Project description:Inflammatory Bowel Diseases (IBD) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective, and affordable, for managing symptoms. Glucosinolate compounds are highly concentrated in broccoli sprouts, especially glucoraphanin, and can be metabolized by certain mammalian gut bacteria into anti inflammatory isothiocyanates, such as sulforaphane. Gut microbiota exhibit biogeographic patterns, but it is unknown if colitis alters these or whether the location of glucoraphanin metabolizing bacteria affects anti-inflammatory benefits. We fed specific pathogen free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet, and gave a three-cycle regimen of 2.5% dextran sodium sulfate (DSS) in drinking water over a 34-day experiment to simulate chronic, relapsing ulcerative colitis. We monitored body weight, fecal characteristics, lipocalin, serum cytokines, and bacterial communities from the luminal and mucosa-associated populations in the jejunum, cecum, and colon. Mice fed the broccoli sprout diet with DSS treatment performed better than mice fed the control diet with DSS, including significantly more weight gain, lower Disease Activity Indexes, lower plasma lipocalin and proinflammatory cytokines, and higher bacterial richness in all gut locations. Bacterial communities were assorted by gut location, but were more homogenous across locations in the control diet + DSS mice. Importantly, our results showed that broccoli sprout feeding abrogated the effects of DSS on gut microbiota, as bacterial richness and biogeography were similar between mice receiving broccoli sprouts with and without DSS. Collectively, these results support the protective effect of steamed broccoli sprouts against dysbiosis and colitis induced by DSS.ImportanceEvaluating bacterial communities across different locations in the gut provides a greater insight than fecal samples alone, and provides an additional metric by which to evaluate beneficial host-microbe interactions. Here, we show that 10% steamed broccoli sprouts in the diet protects mice from the negative effects of dextran sodium sulfate induced colitis, that colitis erases biogeographical patterns of bacterial communities in the gut, and that the cecum is not likely to be a significant contributor to colonic bacteria of interest in the DSS mouse model of ulcerative colitis. Mice fed the broccoli sprout diet during colitis performed better than mice fed the control diet while receiving DSS. The identification of accessible dietary components and concentrations that help maintain and correct the gut microbiome may provide universal and equitable approaches to IBD prevention and recovery, and broccoli sprouts represent a promising strategy.

Dataset Information

Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity.

Publications

Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity.

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