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.

Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis

“…A study of monozygotic twins has revealed significant differences in overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation in older but not in younger twins [14]. A similar result has also been obtained from a longitudinal study in older Swedish monozygotic and dizygotic twins [15], indicative of the environmental effects on epigenetic alterations with age [16]. …”

Synthetic dietary inulin, Fuji FF, delays development of diet-induced obesity by improving gut microbiota profiles and increasing short-chain fatty acid production

“…Most dietary fibers, including inulin, are not digested in the small intestine, but are metabolized by the microbiota in the large intestine (Macfarlane & Macfarlane, 2012). The major SCFA products of microbial fermentation of fibers in the gut are acetic, propionic and butyric acids (Cummings et al, 1987;Matt et al, 2018). Through specific receptors, SCFAs play important roles in the maintenance of health, energy metabolism and the prevention of certain diseases (Alexander et al, 2019;Kimura et al, 2020).…”

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential

“…Butyrate also has anti-inflammatory properties; for instance, butyrate inhibited proinflammatory activities of IECs in vitro (Elce et al, 2017) and interacted with IECs to regulate host T cell responses (Lew et al, 2018;Xu et al, 2018). Butyrate may also diffuse into the systemic circulation to exert anti-inflammatory effects on various organs and tissues, including the brain (McNabney and Henagan, 2017;Matt et al, 2018). Indeed, butyrate has been shown to normalize behavior of depressed rodents through epigenetic regulations of hippocampal BDNF expression (Han et al, 2014;Wei et al, 2014;Sun et al, 2016).…”