The Microbiota-Gut-Brain Axis in Health and Disease and Its Implications for Translational Research

Abstract

Over the past decades, microbiome research has evolved rapidly and became a hot topic in basic, preclinical and clinical research, for the pharmaceutical industry and for the general public. With the help of new high-throughput sequencing technologies tremendous progress has been made in the characterization of host-microbiota interactions identifying the microbiome as a major factor shaping mammalian physiology. This development also led to the discovery of the gut-brain axis as the crucial connection between gut microbiota and the nervous system. Consequently, a rapidly growing body of evidence emerged suggesting that the commensal gut microbiota plays a vital role in brain physiology. Moreover, it became evident that the communication along this microbiota-gut-brain axis is bidirectional and primarily mediated by biologically active microbial molecules and metabolites. Further, intestinal dysbiosis leading to changes in the bidirectional relationship between gut microbiota and the nervous system was linked to the pathogenesis of several psychiatric and neurological disorders. Here, we discuss the impact of the gut microbiota on the brain in health and disease, specifically as regards to neuronal homeostasis, development and normal aging as well as their role in neurological diseases of the highest socioeconomic burden such as Alzheimer’s disease and stroke. Subsequently, we utilize Alzheimer’s disease and stroke to examine the translational research value of current mouse models in the spotlight of microbiome research. Finally, we propose future strategies on how we could conduct translational microbiome research in the field of neuroscience that may lead to the identification of novel treatments for human diseases.

Domestic Environment and Gut Microbiota: Lessons from Pet Dogs

“…Some functions are predicted upward such as the metabolism of tryptophan and phenylalanine and others are predicted downward such as the metabolism of arginine and proline during CKD [ 115 , 116 ]. Patients with end-stage kidney disease on peritoneal dialysis were less likely to have Bifidobacterium catenulatum, Bifidobacterium longum, Bifidobacterium bifidum, Lactobacillus plantarum, Lactobacillus paracasei and Klebsiella pneumoniae than healthy controls [ 117 ]. These populational and functional changes are suspected to be due to the exposure of intestinal bacteria to urea crossing the gut barrier leading to a selection of bacterial families containing urease, uricase or indole- and p-cresyl enzymes [ 118 ].…”

“…Understanding the microbiota–gut–brain axis, with the goal of identifying innovative therapeutic approaches for mental disorders in humans and dogs is a current challenge [ 116 ]. Laboratory animals, and especially germ-free and gnotobiotic mice, have been invaluable tools for proof-of-principle studies demonstrating the impact of the gut microbiota in the healthy development and homeostasis of the nervous system and in psychiatric diseases, autism spectrum disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease and stroke [ 117 ]. Communication between the gut microbiota and the brain takes place via endocrine, immune, humoral and nervous channels, with particular attention given to the vagus nerve [ 118 ].…”

Impacts of changes in intestinal flora on the metabolism of Sprague–Dawley rats

“…Moreover, their relative amounts depended on the presence of specific bacteria. For healthy people, increases in the bifidobacteria and lactobacilli contribute to the catabolism of proteins in the colon [ 36 , 37 ]. In this experiment, the contents of propionic acid and butyric acid in the Salmonella group were lower than those in the normal group, which decreased in the probiotics and gentamicin groups.…”

Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis

“…Innervation of the gut by a network of ENS provides a unique opportunity for gut microbiota to form a multidirectional communication axis with the local neurons, immune cells and also cells of the brain 56 . This forms the microbiota–gut–brain (MGB) axis, which drives a variety of processes including intestinal barrier function, blood–brain barrier (BBB) function and neuroimmune crosstalk to regulate not only brain health 57 but also the development and function of the host defence systems (reviewed in Bistoletti et al 18 and others) 58‐60 …”