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Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.

ABSTRACT: Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4?weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.

SUBMITTER: Matt SM

PROVIDER: S-EPMC6102557 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.

Matt Stephanie M SM Allen Jacob M JM Lawson Marcus A MA Mailing Lucy J LJ Woods Jeffrey A JA Johnson Rodney W RW

Frontiers in immunology 20180814

Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharma ...[more]

PMID: 30154787

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Project description:IntroductionDietary fiber and flavonoids are promising drugs reported in the treatment of inflammatory bowel disease (IBD). However, it is unclear the interaction between dietary fiber and flavonoids in gut health.ObjectiveThe therapeutic effect of celery, kale, and red chicory powders on colitis mice using non-group feeding cages was investigated. Further, the efficacy of whole celery, celery soluble dietary fiber (CSDF), celery insoluble dietary fiber (CIDF), celery flavonoids (CF), CSDF + CF and CIDF + CF in IBD mice model was assessed to dissect protective effect to attribute to which component(s) in such complex matrix.Methods3% Dextran sulfate sodium salt (DSS) was used to induce mice colitis model. Multiple molecular biological methods were employed to evaluate the severity of mice colitis and the gut microbial composition of mice.ResultsAdministration of kale and red chicory significantly restored body weight, DAI score, and colon length in colonic mice, and celery showed the weakest effects. Administration of either CSDF or CF markedly improved the histological damage, increased colonic mucus expression, and reduced colonic MPO/iNOS activities, and IL-6/IL-1β levels. However, CSDF + CF showed weaker improvement than CF or SDF in most physical and biochemical signs. Furthermore, CSDF and CF decreased intestinal g_Escherichia-Shihella and g_Clostridium_sensu_stricto_1 induced by DSS administration. Interestingly, celery flavonoid promoted g_Akkermansia proliferation both in vivo and in vitro, and which can be inhibited by CSDF.ConclusionsThis study revealed for the first time that CSDF can suppress the protective effect of CF on intestinal health by inhibiting g_Akkermansia, and clarified that the decreased efficacy of celery whole food on colitis was mediated by an antagonism between CSDF and CF. Moreover, this study presents for the first time that interaction between soluble dietary fiber and flavonoids in vivo can ameliorate the efficacy of dietary fiber or flavonoids when administered alone suggestive for an antagonistic effect.

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Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.

Publications

Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice.

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