The manometric criterion EGJOO defines a heterogeneous clinical group. While BE, EGD, and EUS all provide complementary information, a significant percentage of these studies will be normal. For patients with dysphagia, outcome may depend on EGJ disruption. There were no differences in symptoms our outcomes based on quantitative EGJ relaxation.

Background and AimsMucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans.MethodsConfocal microscopy was used to measure bacterial-epithelial distance of the closest bacteria per high-powered field in colonic biopsies of all willing participants undergoing cancer screening colonoscopies.ResultsWe observed that, among all subjects, bacterial-epithelial distance was inversely correlated with body mass index, fasting glucose levels, and hemoglobin A1C. However, this correlation was driven by dysglycemic subjects, irrespective of body mass index, whereas the difference in bacterial-epithelial distance between obese and nonobese subjects was eliminated by removal of dysglycemic subjects.ConclusionsWe conclude that microbiota encroachment is a feature of insulin resistance–associated dysglycemia in humans.

Enteric neuronal degeneration, as seen in inflammatory bowel disease, obesity, and diabetes, can lead to gastrointestinal dysmotility. Pyroptosis is a novel form of programmed cell death but little is known about its role in enteric neuronal degeneration. We observed higher levels of cleaved caspase-1, a marker of pyroptosis, in myenteric ganglia of overweight and obese human subjects compared with normal-weight subjects. Western diet-fed (WD-fed) mice exhibited increased myenteric neuronal pyroptosis, delayed colonic transit, and impaired electric field stimulation-induced colonic relaxation responses. WD increased TLR4 expression and cleaved caspase-1 in myenteric nitrergic neurons. Overactivation of nitrergic neuronal NF-κB signaling resulted in increased pyroptosis and delayed colonic motility. In caspase-11-deficient mice, WD did not induce nitrergic myenteric neuronal pyroptosis and colonic dysmotility. To understand the contributions of saturated fatty acids and bacterial products to the steps leading to enteric neurodegeneration, we performed in vitro experiments using mouse enteric neurons. Palmitate and lipopolysaccharide (LPS) increased nitrergic, but not cholinergic, enteric neuronal pyroptosis. LPS gained entry to the cytosol in the presence of palmitate, activating caspase-11 and gasdermin D, leading to pyroptosis. These results support a role of the caspase-11-mediated pyroptotic pathway in WD-induced myenteric nitrergic neuronal degeneration and colonic dysmotility, providing important therapeutic targets for enteric neuropathy.

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Since surgical outcomes for FTMH in MacTel Type 2 may be less successful than typical idiopathic FTMH, it is important to recognize that FTMH may be associated with MacTel. Lower success rate may be because of the pathophysiology of MacTel. The degree of tissue atrophy and appearance of FTMH on optical coherence tomography may guide surgical prognosis.

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