Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons

Abstract

Symbionts or probiotics are known to affect the nervous system. To understand the mechanisms involved, it is important to measure sensory neuron responses and identify molecules responsible for this interaction. Here we test the effects of adding Lactobacillus rhamnosus (JB-1) and Bacteroides fragilis to the epithelium while making voltage recordings from intestinal primary afferent neurons. Sensory responses are recorded within 8 s of applying JB-1 and excitability facilitated within 15 min. Bacteroides fragilis produces similar results, as does its isolated, capsular exopolysaccharide, polysaccharide A. Lipopolysaccharide-free polysaccharide A completely mimics the neuronal effects of the parent organism. Experiments with a mutant Bacteroides fragilis devoid of polysaccharide A shows that polysaccharide A is necessary and sufficient for the neuronal effects. Complex carbohydrates have not been reported before as candidates for such signalling between symbionts and the host. These observations indicate new neuronal targets and invite further study of bacterial carbohydrates as inter-kingdom signalling molecules between beneficial bacteria and sensory neurons.

Converging effects of a Bifidobacterium and Lactobacillus probiotic strain on mouse intestinal physiology

“…The enteric nervous system also appears, although to a lesser degree, to contribute to the effects of B. infantis 35624 on the I sc response elicited after short-term exposure in vitro. It is known, however, that different microbes have the capacity to differentially influence enteric nerve activity (2,14,15,20). For example, Lactobacillus reuteri (15) and Bacteroides fragilis (20) enhance the activity of, or activate, enteric neurons whereas Bifidobacterium longum exerts an inhibitory effect (2,14).…”

“…It is known, however, that different microbes have the capacity to differentially influence enteric nerve activity (2,14,15,20). For example, Lactobacillus reuteri (15) and Bacteroides fragilis (20) enhance the activity of, or activate, enteric neurons whereas Bifidobacterium longum exerts an inhibitory effect (2,14). The inhibitory effect of L. salivarius UCC118, in particular, on enteric nerve activity may be of therapeutic importance in pathogen-mediated diarrheal diseases, particularly those caused by Salmonella spp., Clostridium difficile (13), and rotavirus (19), in which neural pathways have been implicated.…”

The Gut Microbiome and the Brain

“…134 Intrinsic primary afferent neurons (IPANs) are cellular targets of neuroactive bacteria and transmit microbial messages to the brain via the vagus nerve. 135,136 Live bacteria may not be needed for these effects; in the case of B. fragilis, a lipid-free polysaccharide is both necessary and sufficient for IPAN activation. 137 Although the vagus nerve is a critical route for communication between gut microbes and the CNS in some experimental systems, it is not the only route.…”

The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis

“…The experimental evidence gathered using animal model studies indicate the effects of the microbiota in the regulation of EAE in animals (24,(26)(27)(28)(32)(33)(34)(35)(36). Furthermore, gut microbes, such as B. fragilis and Lactobacillus rhamnosus have been shown to interact with neurons in the enteric nervous system (ENS) directly and affect their function (37). The gut microbiota can directly influence hormonal levels, thus modulating the effects of the endocrine system in the autonomous nervous system (38).…”