The Enteric Nervous System and the Microenvironment of the Gut: The Translational Aspects of the Microbiome-Gut-Brain Axis

The proper functioning of the gastrointestinal tract is essential for digestion, absorption and the elimination of waste products. It protects us against pathogens, allergens and toxins, continuously monitoring and regulating the internal environment. The vast majority of these tasks are carried out by the nervous and immune systems of the gut in close cooperation by constantly adapting to internal and external stimuli, maintaining its homeostasis. In this review, we would like to summarize the most recent findings about the cytoarchitecture and functional microanatomy of the enteric nervous system and the immune microenvironment of the gut highlighting the essential role and inevitable molecular crosstalk between these two highly organized networks. Gut neuroimmunology is a rapidly evolving field and might help us to understand the etiology of inflammatory bowel disease and the systemic consequences of chronic intestinal inflammation. Finally, we also included a brief outlook to present the most recent research depicting the multifaceted role of the gut microbiome, its contribution to the gut-brain axis and human disease

The Enteric Nervous System and the Microenvironment of the Gut: The Translational Aspects of the Microbiome-Gut-Brain Axis

The proper functioning of the gastrointestinal tract is essential for digestion, absorption and the elimination of waste products. It protects us against pathogens, allergens and toxins, continuously monitoring and regulating the internal environment. The vast majority of these tasks are carried out by the nervous and immune systems of the gut in close cooperation by constantly adapting to internal and external stimuli, maintaining its homeostasis. In this review, we would like to summarize the most recent findings about the cytoarchitecture and functional microanatomy of the enteric nervous system and the immune microenvironment of the gut highlighting the essential role and inevitable molecular crosstalk between these two highly organized networks. Gut neuroimmunology is a rapidly evolving field and might help us to understand the etiology of inflammatory bowel disease and the systemic consequences of chronic intestinal inflammation. Finally, we also included a brief outlook to present the most recent research depicting the multifaceted role of the gut microbiome, its contribution to the gut-brain axis and human disease

Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model

Abstract Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (l-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent l-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent l-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model