According to a new study performed by University of Illinois researchers and published in Frontiers in Immunology, a diet rich in fiber reduces inflammation in aged mice, both in the guts and the brain. This beneficial reduction is due to high levels of butyrate, which result from the fermentation of fiber during digestion [1].

Study 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 hyper-activation 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 (HDAC) 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 the present 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. Further, 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.

Age-related inflammation and butyrate

Aging is known to worsen virtually every pre-existing medical condition; one of the contributing factors is a state of chronic, systemic, low-grade inflammation, which is known as inflammaging. This constant state of inflammation affects the brain as well, where microglia—the front line of the brain’s immune surveillance system—find themselves in a state of hyperactivity; this, in turn, makes them produce chemicals that end up affecting multiple brain functions in the long run, causing cognitive and motor dysfunction along with other disorders.

Butyrate is a short-chain fatty acid (SCFA) already known to attenuate inflammation and improve cognitive functions in other animal models when administered as sodium butyrate. The authors of this study wanted to see whether the beneficial effects of butyrate could be reproduced in mice, both when directly administered as a drug and when naturally produced through the gut fermentation of fiber.

A fiber-rich diet helps useful, butyrate-producing gut bacteria thrive, unlike diets more rich in fat or protein, which may affect the gut microbiome negatively; while it may seem only reasonable that butyrate produced by a fiber-rich diet should bring the same benefits as butyrate administered as a drug, this was never tested before.







The study

The researchers set up two experiments. First, they administered sodium butyrate through injection to two cohorts of mice, aged 3-6 (adult) and 22-25 (elderly) months, respectively. They found out that this downregulated the expression of pro-inflammatory cytokines in microglia, thereby reducing brain inflammation. Then, they tested the effects of a high-fiber diet versus a low-fiber one on other, similarly aged, mouse cohorts for four weeks.

In both older and younger mice, the high-fiber diet produced elevated levels of butyrate as well as of other SCFAs; the low-fiber diet led to greater inflammation in old mice but, interestingly, not in young mice. Old mice fed the high-fiber diet showed vastly decreased intestinal inflammation levels to the point that there was no appreciable difference in inflammation between the age cohorts.

The beneficial effects of a high-fiber diet were also observed in the brain microglia of aged mice. While this study did not look into whether these changes were also associated with improved cognition, the researchers plan to investigate that in the future.

Conclusion







While the usual rule applies—mice are not people—it’s no mystery that a high-fiber diet is beneficial for humans; it does produce SCFAs, and it may help protect from gastrointestinal disorders, cancer, and heart disease, for example [2]. While more human studies are needed, eating more fiber certainly won’t hurt and, in fact, will probably be good for you.

Literature

[1] Matt, S. M., Allen, J. M., Lawson, M. A., Mailing, L. J., Woods, J. A., & Johnson, R. W. (2018). Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice. Frontiers in Immunology, 9.

[2] Wong, J. M. W., de Souza, R., Kendall, C. W. C., Emam, A., & Jenkins, D. J. A. (2006). Colonic Health: Fermentation and Short Chain Fatty Acids. Journal of Clinical Gastroenterology, 40(3), 235–243.