Targeting Gut Microbiota Dysbiosis: Potential Intervention Strategies for Neurological Disorders

It is well known that the gut microbiota plays an extremely important role in modulating host physiological functions such as immunity and metabolic homeostasis.In recent years,accumulated evidence has revealed that the gut microbiota can regulate the functions of the central nervous system(CNS)through the gut-brain axis,which provides a novel insight into the interactions between the gut and brain.This review focuses on the molecular mechanism of the crosstalk between the gut microbiota and the brain via the gut-brain axis,and on the onset and development of neurological disorders triggered by gut microbiota dysbiosis.These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis,including the use of probiotics,prebiotics,synbiotics,and diets.While research on the microbiota-gut-brain axis is still in its relative infancy,clarifying the molecular mechanism that underlies how the gut microbiota regulates neurological functions not only holds the promise of revealing potentially novel pathogeneses of neurological disorders,but also may lead to the development of potential diagnosis biomarkers and intervention strategies targeting microbiota dysbiosis for neurological disorders.

Infant intestinal Enterococcus faecalis down-regulates inflammatory responses in human intestinal cell lines

AIM: To investigate the ability of Lactic acid bacteria (LAB) to modulate inflammatory reaction in human intestinal cell lines (Caco-2, HT-29 and HCT116). Different strains of LAB isolated from new born infants and fermented milk, together with the strains obtained from culture collections were tested.METHODS: LABs were treated with human intestinal cell lines. ELISA was used to detect IL-8 and TGF-β protein secretion. Cytokines and Toll like receptors (TLRs) gene expression were assessed using RT-PCR. Conditional medium, sonicated bacteria and UV killed bacteria were used to find the effecter molecules on the bacteria. Carbohydrate oxidation and protein digestion were applied to figure out the molecules' residues. Adhesion assays were further carried out.RESULTS: It was found that Enterococcus faecalis is the main immune modulator among the LABs by downregulation of IL-8 secretion and upregulation of TGF-β. Strikingly, the effect was only observed in four strains of E. faecalis out of the 27 isolated and tested. This implies strain dependent immunomodulation in the host. In addition, E. faecalis may regulate inflammatory responses through TLR3, TLR4, TLR9 and TRAF6. Carbohydrates on the bacterial cell surface are involved in both its adhesion to intestinal cells and regulation of inflammatory responses in the host. CONCLUSION: These data provide a case for the modulation of intestinal mucosal immunity in which specific strains of E. faecalis have uniquely evolved to maintain colonic homeostasis and regulate inflammatory responses.

What could probiotic do for us?

Gastrointestinal microbes play important roles in the health and disease of the host.There are many documented evidences which demonstrated that disturbance of intestinal microbiota is linked to the risk of developing infectious,inflammatory and allergic diseases.Human intestine is home for a complex consortium of 1013–1014 microbial cells.Interactions between the intestinal microbes,pathogens and the host lead to exclusion of toxins(mycotoxins)and pathogens(colonization resistance),interference in disease progression as demonstrated in the prevention of oral infection,dental caries,diarrhoeas(Antibiotic Associated Diarrhoea,Travellers’Diarrhoea and Rotavirus Diarrhoea),postoperative infection,respiratory infection and certain cancers.The group of beneficial intestinal microbes termed probiotics alter intestinal epithelial cell tight junction and immunological functions.Lately,laboratory and clinical studies demonstrated gut-brain axis communication and intestinal microbial(both pathogens and probiotics)modulation of host psycho-neuroimmunological functions,in relation to depression,anxiety and memory dysfunction.These open up many possibilities of probiotics supplementation for moderating intestinal microbiota as an approach in disease prevention and treatment.