Intestinal macrophages are the most abundant immune cells in our gut but understanding of their function is impeded by their heterogeneity. In this review we dissect different subtypes of intestinal macrophages and highlight their roles in several gastrointestinal (GI) disorders.Intestinal macrophages play a key role in the gut immune system and the regulation of gastrointestinal physiology, including gut motility and secretion. Their ability to keep the gut from chronic inflammation despite constantly facing foreign antigens has been an important focus in gastrointestinal research. However, the heterogeneity of intestinal macrophages has impeded our understanding of their specific roles. It is now becoming clear that subsets of intestinal macrophages play diverse roles in various gastrointestinal diseases. This occurs through a complex interplay between cytokine production and enteric nervous system activation that differs for each pathologic condition. Key diseases and disorders in which intestinal macrophages play a role include postoperative ileus, inflammatory bowel disease, necrotizing enterocolitis, as well as gastrointestinal disorders associated with human immunodeficiency virus and Parkinson's disease. Here, we review the identification of intestinal macrophage subsets based on their origins and functions, how specific subsets regulate gut physiology, and the potential for these heterogeneous subpopulations to contribute to disease states. Furthermore, we outline the potential for these subpopulations to provide unique targets for the development of novel therapies for these disorders.

Gastrointestinal motility is crucial to gut health and has been associated with different disorders such as inflammatory bowel diseases and post-operative ileus. Despite rat and mouse being the two animal models most widely used in gastrointestinal research, minimal studies in rats have investigated gastrointestinal motility. Therefore, our study provides a comparison of colonic motility in the mouse and rat to clarify species differences and assess the relative effectiveness of each animal model for colonic motility research. To our knowledge, this is the first study to use ex vivo video imaging techniques to assess rat colonic motility. We identified differences in the histology of the proximal colon such that the rat had larger villus height-to-width and villus height-to-crypt depth ratios compared with mouse. Since gut motility is tightly regulated by the enteric nervous system (ENS), we investigated how colonic contractile activity within each species responds to modulation of the ENS inhibitory neuronal network. Here we used Nω‐nitro‐l‐arginine (NOLA), an inhibitor of nitric oxide synthase (NOS) to assess proximal colon responses to the stimulatory effect of blocking the major inhibitory neurotransmitter, nitric oxide (NO). In rats, the frequency of proximal colonic contractions increased in the presence of NOLA (versus control levels) to a greater extent than in mice. This is despite a similar number of NOS-expressing neurons in the myenteric plexus across species. Given this increase in colonic contraction frequency, the rat represents another relevant animal model for investigating how gastrointestinal motility is regulated by the inhibitory neuronal network of the ENS.

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