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Disorders of gut-brain interaction (DGBIs) are common conditions in community and clinical practice. As specialized enteroendocrine cells, enterochromaffin (EC) cells produce up to 95% of total body serotonin and coordinate luminal and basolateral communication in the gastrointestinal (GI) tract. EC cells affect a broad range of gut physiological processes, such as motility, absorption, secretion, chemo/mechanosensation, and pathologies, including visceral hypersensitivity, immune dysfunction, and impaired gastrointestinal barrier function. We aim to review EC cell and serotonin-mediated physiology and pathophysiology with particular emphasis on DGBIs. We explored the knowledge gap and attempted to suggest new perspectives of physiological and pathophysiological insights of DGBIs, such as (1) functional heterogeneity of regionally distributed EC cells throughout the entire GI tract; (2) potential pathophysiological mechanisms mediated by EC cell defect in DGBIs; (3) cellular and molecular mechanisms characterizing EC cells and gut microbiota bidirectional communication; (4) differential modulation of EC cells through GI segment-specific gut microbiota; (5) uncover whether crosstalk between EC cells and (i) luminal contents; (ii) enteric nervous system; and (iii) central nervous system are core mechanisms modulating gut-brain homeostasis; and (6) explore the therapeutic modalities for physiological and pathophysiological mechanisms mediated through EC cells. Insights discussed in this review will fuel the conception and realization of pathophysiological mechanisms and therapeutic clues to improve the management and clinical care of DGBIs. [ABSTRACT FROM AUTHOR]

Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background/Aims Irritable bowel syndrome (IBS) is associated with exaggerated cerebral response including emotional processing following visceral stimulation; though data on this issue is available in female IBS patients, it is scanty among males. Hence, we aimed to study brain response of male IBS patients following rectal balloon distension as compared to healthy controls using functional magnetic resonance imaging (fMRI). Data between diarrhea and constipation predominant IBS (IBS-D and IBS-C) were also compared. Methods Rectal balloon distension threshold was assessed in 20 male IBS patients (10 IBS-C and 10 IBS-D) and 10 age-matched male healthy controls. Subsequently, fMRI on all the participants was performed at their respective rectal pain threshold. The fMRI data were analysed using the Statistical Parametric Mapping software. Results IBS patients showed greater cerebral activations in insula, middle temporal gyrus, and cerebellum in the left hemisphere compared to healthy controls. Neural activation was found in bilateral precuneus/superior parietal lobules in controls but not in patients with IBS. The brain activation differed among IBS-C and IBS-D patients; while the right mid-cingulate cortex was activated in IBS-C, the left inferior orbito-frontal cortex, left calcarine, and bilateral fusiform gyri were activated among patients with IBS-D following rectal balloon distension. Conclusions Brain response to rectal balloon distension differed among male patients with IBS and controls and among patients with IBS-C and IBS-D. Differential activation among patients with IBS-C and IBS-D was seen in the brain regions controlling affective motivation, homeostatic emotions, and autonomic responses to pain. [ABSTRACT FROM AUTHOR]

Background/Aims: Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. Methods:Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. Results: Of the 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9-4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0-315] vs 159 [69-287] minutes, P = 0.500; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.620, respectively). Conclusions: Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole. [ABSTRACT FROM AUTHOR]

Background/Aims: Achalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), produced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic polymorphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS). Methods: Consecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. Results: Among 183 patients (118 [64.5%] male, age 39.5 ± 13.0 years) with achalasia and 366 HS (254 [69.4%] male, age 40.8 ± 11.0 years), eNOS4a4a genotype of 27-bp VNTR was more common among achalasia than HS (20 [10.9%] vs 13 [3.6%]; P < 0.001; OR, 3.72; 95% CI, 1.8-7.7). Patients with achalasia had iNOS22GA genotypes more often than HS (95 [51.9%] vs 93 [25.4%]; P < 0.001; OR, 3.0; 95% CI, 2.1-4.4). Frequency of genotypes GA + AA was higher in patients than HS (97 [53%] vs 107 [29.2%]; P < 0.001; OR, 2.7; 95% CI, 1.8-3.9). Also, nNOS29TT variant genotype in rs2682826 was more com - mon among patients compared to HS (14 [7.7%] vs 6 [1.6%]; P < 0.001; OR, 5.91; 95% CI, 2.2-15.8). Conclusions: Achalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia. [ABSTRACT FROM AUTHOR]

The author reflects on the role of genetic factors in occurrence of irritable bowel syndrome (IBM). He makes reference to a study published in the journal which evaluates association between IBM and serotonin transporter (SLC6A4) polymorphism. The study reveals that patients with constipation predominant IBS (IBS-C) showed reduced level of serum serotonin as compared to patient with diarrhea predominant IBS (IBS-D).