Short‐chain fatty acids: microbial metabolites that alleviate stress‐induced brain–gut axis alterations

Abstract

There is a growing recognition of the involvement of the gastrointestinal microbiota in the regulation of physiology and behaviour. Microbiota-derived metabolites play a central role in the communication between microbes and their host, with short-chain fatty acids (SCFAs) being perhaps the most studied. SCFAs are primarily derived from fermentation of dietary fibres and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress. Therefore, we sought to assess whether SCFA supplementation could counteract the enduring effects of chronic psychosocial stress. C57BL/6J male mice received oral supplementation of a mixture of the three principle SCFAs (acetate, propionate and butyrate). One week later, mice underwent 3 weeks of repeated psychosocial stress, followed by a comprehensive behavioural analysis. Finally, plasma corticosterone, faecal SCFAs and caecal microbiota composition were assessed. SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress. Stress-induced increases in body weight gain, faecal SCFAs and the colonic gene expression of the SCFA receptors free fatty acid receptors 2 and 3 remained unaffected by SCFA supplementation. Moreover, there were no collateral effects on caecal microbiota composition. Taken together, these data show that SCFA supplementation alleviates selective and enduring alterations induced by repeated psychosocial stress and these data may inform future research into microbiota-targeted therapies for stress-related disorders.

Supplementation of dietary non-digestible oligosaccharides from birth onwards improve social and reduce anxiety-like behaviour in male BALB/c mice

“…Changes in intestinal microbiota can affect brain and behaviour through the gut-brain axis through several mechanisms, including microbe-derived molecules like SCFAs, and tryptophan metabolites neuroactive molecules like neurotransmitters and neuronal signalling by stimulation of the vagus nerve [57]. As SCFAs are fermentation products from scGOS:lcFOS and SCFAs have been shown to reduce anxiety-like and depressive-like behaviour in mice [58], these mediators might play a role in the behavioural changes observed in our study. How this communication between the SCFAs and the brain occurs is unknown, however, signalling through the vagus nerve [10] or improved integrity of the blood brain barrier could play a role [59].…”

The therapeutic efficacy of Bifidobacterium animalis subsp. lactis BB‐12® in infant colic: A randomised, double blind, placebo‐controlled trial

“…34 Butyrate modulates intestinal transit time, visceral and central pain perception and gut-brain axis, and exerts a potent anti-inflammatory action. [35][36][37][38][39][40][41][42][43][44][45][46] The faecal calprotectin features have been explored by only few authors with conflicting results. 47,48 We found a different modulation of calprotectin in responder infants to BB-12…”

Microbiota-derived short chain fatty acids promote Aβ plaque deposition

“…In a Parkinson's disease mouse model, SCFA were sufficient to induce neuroinflammation and disease progression in absence of the gut microbiome (Sampson et al, 2016). Moreover, SCFA have been implicated in a wide range of brain disorders or physiological functions under cerebral control such as mood disorders, autism spectrum disease or energy metabolism (Cryan et al, 2019;Li et al, 2018;van de Wouw et al, 2018).…”