How can the study of gut microbiota lead to future treatments for neurological disorders?
Studies have linked gut microbiota to a slew of pathological conditions ranging from autism to allergy, but can these findings help us to treat neurological disorders?
In preparation for a new semester of teaching, I picked up Alanna Collen’s recent book, 10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness.1 In this book, Dr. Collen explains the intricate connection between gut microbiota and the nervous system by telling the story of the Bolte family. Ellen Bolte, whose son Andrew developed autism shortly after being treated with antibiotics for an ear infection, has persuaded the medical community to consider the possibility that the two events are connected. Since then, many medical researchers have explored this connection. Along the way, new associations have emerged, for example, the association of multiple sclerosis (MS) with certain components of gut microbiota.
As research of the connection of gut microbiota and MS advanced, the role of the immune system, specifically, CD4+ T regulatory cells (Tregs), became apparent. In experimental autoimmune encephalomyelitis, a mouse model of MS, Tregs are abundant in mucosa of the colon wall. The presence of Tregs in the gut has a special implication: these cells are in the immediate proximity to gut microbiota. In vivo studies have identified specific strains of microorganisms that affect Tregs and through them, the course of MS. For example, a bacterial capsular polysaccharide Ag produced by human commensal bacteria Bacteroides fragilis stimulates Tregs to suppress autoimmune processes and to in turn protect mice against demyelination.2
A recent study by Miyake and colleagues published in PLoS One continues the conversation by describing microbiota species deficient in patients with MS.3 The authors of the study have recruited 20 patients with relapsing-remitting MS and 40 healthy volunteers to provide fecal samples. Analysis of bacterial RNA has revealed differences in 21 species of bacteria between healthy volunteers and patients with MS. Most of the identified species belong to taxa Clostridia (clusters XIVa and IV) and Bacteroidetes. Both taxa have been linked to autoimmune disease, however, exact Clostridia species that this study identified as less common in MS have not yet been linked to autoimmune conditions. Identified Bacteroidetes species have been previously linked to rheumatoid arthritis and autism.
This study is one of the first to describe the differences in microbiota of healthy individuals and patients with MS. To my knowledge, transplantation of bacteria capable of modifying the course of MS is yet to be investigated in clinical trials, but it has already been done in vivo in preclinical studies. Fecal microbiota transplantation is currently in clinical trials for several nonneurological indications. What if a capsule of freeze-dried bacteria or an enema with bacterial preparation can free a patient with MS of relapses?
Key points and questions:
• Gut microbiota modifies autoimmune processes via regulatory T cells.
• Specific differences in gut microbiota of patients with MS and healthy individuals have been identified.
• What obstacles do you see on the way to adoption of microbiotic therapies for the treatment of MS?
1. Collen A. 10% Human: How Your Body’s Microbes Hold the Key to Health and Happiness. New York: HarperCollins; 2015.
2. Ochoa-RepÃ¡raz J, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol. 2010;185(7):4101-4108.
3. Miyake S, et al. Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to Clostridia XIVa and IV clusters. PLoS One. 2015;10(9):e0137429.