New methods to unveil host-microbe interaction mechanisms along the microbiota-gut-brain-axis.

Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used in vivo and in vitro models, their implications, and perspectives in the field based on a systematic review of PubMed. Applications of various animal models (zebrafish, mouse, canine, rat, rabbit) to microbiota-gut-brain axis research with practical examples of in vitro methods and innovative approaches to studying gut-brain communications are highlighted. In particular, we extensively discuss the potential of "organ-on-a-chip" devices and their applications in this field. Overall, this review sheds light on the most widely used models and methods, guiding researchers in the rational choice of strategies for studies of microbiota-gut-brain interactions.

Association of gut-specific non-inflammatory T lymphocytes with chronic anorexia nervosa and constitutional thinness.

OBJECTIVE: Previous studies of AN showed low-grade inflammation. Are low-grade inflammation and circulating lymphocytes associated with chronic conditions? METHOD: Peripheric blood cytokines were measured using Luminex™ technology in a chronic AN cohort (mean = 67.42 months), compared to Constitutional Thinness (CT), Constitutional Obesity (CO), and Healthy Controls (HC). Secondarily a prospective cohort of chronic AN (mean = 54.11 months) was recruited to compare the functional lymphocyte profile in blood by flow cytometry to CT and HC. RESULTS: In the AN group, most cytokine concentrations were lower than in CT and HC groups. The IL-23 (98.02 pg/ml) was elevated related to HC and CO, and the IL-10 (4.178 pg/ml) was elevated versus CO. In the CT group, IL-9 (0.06216 pg/ml) was elevated compared to AN. The AN group had high Treg (9.259% of CD4+ ) and CD8+ Integrinß7+ (9.552% of CD3+ ) versus HC for lymphocyte populations. In CT group, elevated Treg (9.7% of CD4+ ) elevated percentage of CD4+ CCR9+ (5.867% of CD3+ ) and CD8+ Integrinß7+ (10.21% of CD3+ ) were found versus HC. CONCLUSIONS: The chronic state of AN and CT is surprisingly non-inflammatory with elevated Treg cells. These results suggest that maintaining a dysregulated response to intestinal antigens may contribute to maintaining AN.

Anorexia Nervosa and Autism Spectrum Disorders: Future Hopes Linked to Mucosal Immunity.

Mental health is becoming a public health priority worldwide. Anorexia nervosa and autism spectrum disorders are 2 important types of childhood disorders with a bad prognosis. They share cognitive impairments and, in both cases, the microbiota appears to be a crucial factor. Alteration of the microbiota-gut-brain axis is an appealing hypothesis to define new pathophysiological mechanisms. Mucosal immunity plays a key role between the microbiota and the brain. The mucosal immune system receives and integrates messages from the intestinal microenvironment and the microbiota and then transmits the information to the nervous system. Abnormalities in this sensorial system may be involved in the natural history of mental diseases and might play a role in their maintenance. This review aims to highlight data about the relationship between intestinal mucosal immunity and these disorders. We show that shared cognitive impairments could be found in these 2 disorders, which both present dysbiosis. This literature review provides details on the immune status of anorexic and autistic patients, with a focus on intestinal mucosal factors. Finally, we suggest future research hypotheses that seem important for understanding the implication of the gut-brain-axis in psychiatric diseases.