Impact of Gut Microbiota on the Peripheral Nervous System in Physiological, Regenerative and Pathological Conditions

Abstract

It has been widely demonstrated that the gut microbiota is responsible for essential functions in human health and that its perturbation is implicated in the development and progression of a growing list of diseases. The number of studies evaluating how the gut microbiota interacts with and influences other organs and systems in the body and vice versa is constantly increasing and several ‘gut–organ axes’ have already been defined. Recently, the view on the link between the gut microbiota (GM) and the peripheral nervous system (PNS) has become broader by exceeding the fact that the PNS can serve as a systemic carrier of GM-derived metabolites and products to other organs. The PNS as the communication network between the central nervous system and the periphery of the body and internal organs can rather be affected itself by GM perturbation. In this review, we summarize the current knowledge about the impact of gut microbiota on the PNS, with regard to its somatic and autonomic divisions, in physiological, regenerative and pathological conditions.

Gut microbiota depletion delays somatic peripheral nerve development and impairs neuromuscular junction maturation

“…Our results are in accordance with studies on the enteric nervous system (ENS), a branch of the PNS that provides intrinsic innervation of the bowel. 16 , 31 Early exposure to intestinal bacteria is essential for ENS postnatal development. GF mice show reduced nerve fiber density and fewer neuronal cells in their myenteric plexus compared to specific pathogen-free mice.…”

“…Acetate, propionate, and butyrate are the main short-chain fatty acids produced by bacterial fermentation of dietary fibers and resistant starch, and growing evidence supports the idea that they exert crucial physiological effects on several organs, including the central and enteric nervous system. 16 , 56 Recently, the impact of neonatal antibiotics-induced dysbiosis on the gut-brain axis, including myelination, has been studied, showing that neonatal antibiotics administration led to increased myelination in the prefrontal cortex in adulthood. Interestingly, these alterations were restored by butyrate administration, 36 suggesting a critical role of butyrate in the process of CNS myelination.…”

“…Microbiota-derived metabolites and other products, such as peptides and neuroactive substances, affect CNS development and function 1 and are expected to similarly impact on the peripheral nervous system (PNS). 16 Peripheral nerves originate from the neuroectoderm and elongate with the growth and development of mesodermal somites, which further develop into bone and muscle tissue. Schwann cells, glial cells of the PNS, and dorsal root ganglion neurons, develop from the ectodermal neural crests; peripheral nerves and skeletal muscle or sensory target tissue build an interdependent unit.…”

“…To the best of our knowledge, no studies have reported whether gut microbiota regulates the development or function of somatic PNS in healthy/physiological conditions. While the impact of gut microbiota on the development of the enteric nervous system (a branch of the PNS located within the walls of the gastrointestinal tract) and its functional target tissues appears to be clear, 16–18 the impact of gut microbiota on the communication and functional dependence of somatic nerves and their target tissues remains to be revealed. Based on the presented results, we contribute new knowledge to fill this gap.…”

Latest Review Papers in Molecular Microbiology

“…The influence of intestinal microbiota on the peripheral nervous system is summarized by Calabrò et al [ 2 ]. As described in this paper, the gut microbiota influences the regeneration of nerve injuries as well as the function of the autonomic nervous system and the skeletal muscle.…”