Abstract
In the last decade, emerging evidence has reported correlations between the gut microbiome and human health and disease, including those affecting the brain. We performed a systematic assessment of the available literature focusing on gut bacterial metabolites and their associations with diseases of the central nervous system (CNS). The bacterial metabolites short-chain fatty acids (SCFAs) as well as non-SCFAs like amino acid metabolites (AAMs) and bacterial amyloids are described in particular. We found significantly altered SCFA levels in patients with autism spectrum disorder (ASD), affective disorders, multiple sclerosis (MS) and Parkinson’s disease (PD). Non-SCFAs yielded less significantly distinct changes in faecal levels of patients and healthy controls, with the majority of findings were derived from urinary and blood samples. Preclinical studies have implicated different bacterial metabolites with potentially beneficial as well as detrimental mechanisms in brain diseases. Examples include immunomodulation and changes in catecholamine production by histone deacetylase inhibition, anti-inflammatory effects through activity on the aryl hydrocarbon receptor and involvement in protein misfolding. Overall, our findings highlight the existence of altered bacterial metabolites in patients across various brain diseases, as well as potential neuroactive effects by which gut-derived SCFAs, p-cresol, indole derivatives and bacterial amyloids could impact disease development and progression. The findings summarized in this review could lead to further insights into the gut–brain–axis and thus into potential diagnostic, therapeutic or preventive strategies in brain diseases.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Direct impacts on brain cells by short-chain fatty acids (SCFAs) seem to be complex as well as dosedependent, which supports a hypothesis that anti-inflammatory processes in the brain, neuroplasticity and neurogenesis could be positively modulated through the manipulation of gut bacterial production and/or external supplementation of SCFAs
It was suggested that SCFAs could amend the faulty colonic NLRP6 inflammasome responsible for epithelial impairment to alleviate hippocampal neuroinflammation, possibly reducing the likelihood of neurodegenerative processes associated with a typically high-fructose Western-style diet [88]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. We are exposed to bacterial organisms from the beginning of our existence to the end of it. Bacteria have been detected in the meconium of newborns, discrediting the pre-existing idea of a sterile foetal stage [1]. The early postnatal exposure to either the mother’s vaginal flora or microbes from the environment, depending on delivery, impacts microbial colonization patterns, overall health and the neurodevelopment of the individual [2]. The microbial residents in our gastrointestinal tract (GIT) have already been known to impact the state of human health, the theory of a bidirectional gut–brain–axis (GBA) has taken the spotlight of global researchers mostly after the turn of the millennium
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