Changing eating habits and an increase in consumption of thermally processed products have increased the risk of the harmful impact of chemical substances in food on consumer health. A 2002 report by the Swedish National Food Administration and scientists at Stockholm University on the formation of acrylamide in food products during frying, baking and grilling contributed to an increase in scientific interest in the subject. Acrylamide is a product of Maillard\'s reaction, which is a non-enzymatic chemical reaction between reducing sugars and amino acids that takes place during thermal processing. The research conducted over the past 20 years has shown that consumption of acrylamide-containing products leads to disorders in human and animal organisms. The gastrointestinal tract is a complex regulatory system that determines the transport, grinding, and mixing of food, secretion of digestive juices, blood flow, growth and differentiation of tissues, and their protection. As the main route of acrylamide absorption from food, it is directly exposed to the harmful effects of acrylamide and its metabolite-glycidamide. Despite numerous studies on the effect of acrylamide on the digestive tract, no comprehensive analysis of the impact of this compound on the morphology, innervation, and secretory functions of the digestive system has been made so far. Acrylamide present in food products modifies the intestine morphology and the activity of intestinal enzymes, disrupts enteric nervous system function, affects the gut microbiome, and increases apoptosis, leading to gastrointestinal tract dysfunction. It has also been demonstrated that it interacts with other substances in food in the intestines, which increases its toxicity. This paper summarises the current knowledge of the impact of acrylamide on the gastrointestinal tract, including the enteric nervous system, and refers to strategies aimed at reducing its toxic effect.

UNASSIGNED: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer\'s disease, Parkinson\'s disease, and Multiple Sclerosis (MS).
UNASSIGNED: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer\'s disease, followed by Parkinson\'s disease, and then little in MS. The data for MS is encouraging despite this.
UNASSIGNED: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.

Postoperative ileus (POI) is caused by enteric neural dysfunction and inflammatory response to the stress of surgery as well as the effect of anesthetics and opioid pain medications. POI results in prolonged hospital stays, increased medical costs, and diminished enteral nutrition, rendering it a problem worth tackling. Many cellular pathways are implicated in this disease process, creating numerous opportunities for targeted management strategies. There is a gap in the literature in studies exploring neonatal POI pathophysiology and treatment options. It is well known that neonatal immune and enteric nervous systems are immature, and this results in gut physiology which is distinct from adults. Neonates undergoing abdominal surgery face similar surgical stressors and exposure to medications that cause POI in adults. In this review, we aim to summarize the existing adult and neonatal literature on POI pathophysiology and management and explore applications in the neonatal population.

Endometriosis is a chronic inflammatory disease where endometrial-like lesions settle outside the uterus, resulting in extensive inflammatory reactions. It is a complex disease that presents with a range of symptoms, with pain and infertility being the most common. Along with severe dysmenorrhea, cyclic and acyclic lower abdominal pain, cyclic dysuria and dyschezia, dyspareunia, and infertility, there are also nonspecific complaints that can cause confusion and make endometriosis the chameleon among gynecological diseases. These symptoms include unspecific intestinal complaints, cyclic diarrhea, but also constipation, nausea, vomiting, and stomach complaints. It appears that in addition to general bowel symptoms, there are also specific symptoms related to endometriosis such as cyclic bloating of the abdomen, known as endo belly. During the second half of the menstrual cycle leading up to menstruation, the abdomen becomes increasingly bloated causing discomfort and pain due to elevated sensitivity of the intestinal wall. Patients with endometriosis exhibit a reduced stretch pain threshold of the intestinal wall. Here, we review the endo belly, for the first time, pathophysiology and the influence of other diseases (such as irritable bowel syndrome-IBS), microbiome, hormonal levels, inflammation, and diet on the presentation of this condition.

Motor function of the colon is essential for health. Our current understanding of the mechanisms that underlie colonic motility are based upon a range of experimental techniques, including molecular biology, single cell studies, recordings from muscle strips, analysis of part or whole organ ex vivo through to in vivo human recordings. For the surgeon involved in the clinical management of colonic conditions this amounts to a formidable volume of material. Here, we synthesize the key findings from these various experimental approaches so that surgeons can be better armed to deal with the complexities of the colon.

The tumor microenvironment corresponds to a complex mixture of bioactive products released by local and recruited cells whose normal functions have been \"corrupted\" by cues originating from the tumor, mostly to favor cancer growth, dissemination and resistance to therapies. While the immune and the mesenchymal cellular components of the tumor microenvironment in colon cancer have been under intense scrutiny over the last two decades, the influence of the resident neural cells of the gut on colon carcinogenesis has only very recently begun to draw attention. The vast majority of the resident neural cells of the gastrointestinal tract belong to the enteric nervous system and correspond to enteric neurons and enteric glial cells, both of which have been understudied in the context of colon cancer development and progression. In this review, we especially discuss available evidence on enteric glia impact on colon carcinogenesis. To highlight \"corrupted\" functioning in enteric glial cells of the tumor microenvironment and its repercussion on tumorigenesis, we first review the main regulatory effects of enteric glial cells on the intestinal epithelium in homeostatic conditions and we next present current knowledge on enteric glia influence on colon tumorigenesis. We particularly examine how enteric glial cell heterogeneity and plasticity require further appreciation to better understand the distinct regulatory interactions enteric glial cell subtypes engage with the various cell types of the tumor, and to identify novel biological targets to block enteric glia pro-carcinogenic signaling.

Enteric glial cells in the enteric nervous system are critical for the regulation of gastrointestinal homeostasis. Increasing evidence suggests two-way communication between enteric glial cells and both enteric neurons and immune cells. These interactions may be important in the pathogenesis of Crohn\'s disease (CD), a chronic relapsing disease characterized by a dysregulated immune response. Structural abnormalities in glial cells have been identified in CD. Furthermore, classical inflammatory pathways associated with CD (e.g., the nuclear factor kappa-B pathway) function in enteric glial cells. However, the specific mechanisms by which enteric glial cells contribute to CD have not been summarized in detail. In this review, we describe the possible roles of enteric glial cells in the pathogenesis of CD, including the roles of glia-immune interactions, neuronal modulation, neural plasticity, and barrier integrity. Additionally, the implications for the development of therapeutic strategies for CD based on enteric glial cell-mediated pathogenic processes are discussed.

Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a \'reactive glial phenotype\' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, \'leaky gut\', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α-2 (α-2R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology.

Enteric glial cells represent the enteric population of peripheral glia. According to their \'glial\' nature, their principal function is to support enteric neurons in both structural and functional ways. Mounting evidence however demonstrates that enteric glial cells crucially contribute to the majority of enteric nervous system functions, thus acting as pivotal players in the maintenance of gut homeostasis. Various types of enteric glia are present within the gut wall, creating an intricate interaction network with other gastrointestinal cell types. Their distribution throughout the different layers of the gut wall translates in characteristic phenotypes that are tailored to the local tissue requirements of the digestive tract. This heterogeneity is assumed to be mirrored by functional specialization, but the extensive plasticity and versatility of enteric glial cells complicates a one on one phenotype/function definition. Moreover, the relative contribution of niche-specific signals versus lineage determinants for driving enteric glial heterogeneity is still uncertain. In this review we focus on the current understanding of phenotypic and functional enteric glial cell heterogeneity, from a microenvironmental and developmental perspective.

In the body, nerve tissue is not only present in the central nervous system, but also in the periphery. The enteric nervous system (ENS) is a highly organized intrinsic network of neurons and glial cells grouped to form interconnected ganglia. Glial cells in the ENS are a fascinating cell population: their neurotrophic role is well established, as well as their plasticity in specific circumstances. Gene expression profiling studies indicate that ENS glia retain neurogenic potential. The identification of neurogenic glial subtype(s) and the molecular basis of glia-derived neurogenesis may have profound biological and clinical implications. In this review, we discuss the potential of using gene-editing for ENS glia and cell transplantation as therapies for enteric neuropathies. Glia in the ENS: target or tool for nerve tissue repair?