The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication.

A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.

Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

Gut microbiome production of short-chain fatty acids and obesity in children.

Obesity has been a worldwide multifactorial epidemic malady for the last 2 decades. Changes in gut microbiota composition and its metabolites - short-chain fatty acids (SCFAs) - have been associated with obesity. Recent evidence suggests that SCFAs made by the gut microbiota may regulate directly or indirectly physiological and pathological processes in relation to obesity. We review the influence of gut microbiota in energy, glucose, and lipid homeostasis control via their metabolites. Gut microbial disturbances in obese children may have a role in their metabolism. At first glance, excessive short-chain fatty acids produced by a particular gut microbiota represent an additional energy source, and should cause an imbalance in energy regulation, contributing to obesity. However, simultaneously, SCFA participates in glucose-stimulated insulin secretion from the pancreatic ß-cells through interaction with the FFA2 and FFA3 receptors, and release of peptide hormones which control appetite. This apparent contradictory situation may indicate the involvement of additional particular bacteria or bacterial components or metabolites that may trigger regulatory cascades by interaction with some G-protein-coupled membrane receptors.

Acidos graxos de cadeia curta e doenças colorretais / Short-chain fatty acids and colorectal diseases

O cólon humano contribui de maneira importante para a fermentaçäo de polissacárides näo absorvidos, produzindo ácidos graxos de cadeia curta (AGCC). Este artigo analisa a importância fisiológica dos AGCC para os colonócitos e as perspectivas de sua utilizaçäo clínica no tratamento das doenças colorretais. Diversos efeitos benéficos säo atribuídos ao processo de fermentaçäo e à subsequente produçäo de AGCC, como a contribuiçäo às necessidades energéticas, à manutençäo da integridade e funçäo da mucosa colônica e implicaçöes no metabolismo nitrogenado, de lipídes e glicídios. Além disso, diversas afecçöes colorretais tem sido relacionadas a deficiência de AGCC, como a colite por desuso, colite ulcerativa, bolsite pós-proctocolectomia com anastomose íleo-anal e câncer colorretal. Por este motivo, o fornecimento de AGCC diretamente à mucosa intestinal ou por via intravenosa tem sido preconizado em diversas condiçöes clínicas

Modulación neuroendocrina de los efectos enterotróficos de los ácidos grasos de cadena corta colónicos

Los efectos enterotróficos de los ácidos grasos de cadena corta son cadena complejos y problabemente multifatoriales. La adición directa de energía a la mucosa intestinal es una contribución moderada, mientras que el incremento en el flujo sanguíneo puede aportar una contribución ligeramente mayor al enterotrofismo. Los mecanismos mediados localmente solos, como se describe, no pueden explicar por completo los efectos tróficos de los ácidos grasos de cadena corta, debido a que el trofismo intestinal se presenta tanto local como distalmente al sitio de infusión. Los ácidos grasos de cadena corta estimulan el crecimiento del intestino delgado, lo mismo que del intestino grueso cuando se infunden al colon de ratas. El incremento de las secreciones endocrinas pancreáticas, la estimulación de las hormonas gastrointestinales enterotróficas y el incremento en el sistema nervioso autónomo pueden ser mediadores adicionales, tanto de los efectos enterotróficos locales, como de los efectos enterotróficos sistémicos de los ácidos grasos de cadena corta. Definir los mensajeros hormonales específicos y los procesos celulares mediante los cuales son liberados, es una área muy activa de la investigación actualmente en marcha.