Contraction reserve in high resolution manometry is correlated with lower esophageal acid exposure time in patients with normal esophageal motility: A retrospective observational study.

BACKGROUND: In high resolution manometry (HRM), distal contractile integral post multiple rapid swallow augmentation is considered as contraction reserve. The relationship between contraction reserve and esophageal acid reflux remains unclear. The aim of this study was to explore the correlation between contraction reserve and esophageal acid exposure in ineffective esophageal motility (IEM) and normal HRM. METHODS: Patients who underwent HRM and ambulatory reflux monitoring were retrospectively screened. Those with diagnosis of normal HRM or IEM were included in the analysis. The proportion of patients with abnormal acid exposure time (AET) was compared between patients with and without contraction reserve. Multivariate regression analysis was performed to determine the predictors of abnormal AET and contraction reserve. RESULTS: A total of 338 patients, including 264 normal HRM and 74 IEM, were included in the analysis. In patients with normal HRM, proportion of abnormal total AET (AET > 6.0%) was significantly lower in patients with supine contraction reserve than patients without contraction reserve (13.85% vs. 24.63%, p = 0.027). Multivariate regression analysis showed that supine contraction reserve could independently predict abnormal total AET (OR = 0.468, 95% CI: 0.249-0.948, p = 0.034), while upright contraction reserve trended strongly (OR = 0.558, 95% CI: 0.290-1.071, p = 0.079). Subgroup analysis showed that upright contraction reserve was an independent predictor of abnormal total AET in patients with 50-70% infective swallows (OR = 0.205, 95% CI: 0.051-0.821, p = 0.025), whereas supine contraction reserve did not have predictive value (p = 0.359). CONCLUSIONS: Supine contraction reserve correlates with esophageal acid reflux in patients with normal HRM, while only upright contraction reserve correlates with esophageal acid reflux in patients with infective swallows of 50-70%.

Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.

Objective: To study the effect of precision probiotic strains transplantation capsules on diarrhea irritable bowel syndrome compared with fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules. Methods: Two patients with severe irritable bowel syndrome were treated with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules in sequence. IBS-SSS, IBS-QoL, GSRS, stool frequency, stool character, degree of abdominal pain, GAD-7, and PHQ9 scores of patients at 0, 2, 4, 6, 8, 10, and 12 weeks of treatment were monitored and recorded, and stool samples were collected for metagenomics and metabolomics. Results: It was found that the IBS-SSS score of patient case 1 decreased by 175 points and that of patient case 2 decreased by 100 points after treatment of precision probiotic strains transplantation capsules. There was no significant decrease after fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules were used. At the same time, compared with fecal microbiota transplantation and live combined bacillus subtilis and enterococcus faecium capsules, the IBS QoL, stool frequency, stool character, degree of abdominal pain and GAD-7 score of patient case 1 improved more significantly by the precision probiotic strains transplantation capsules. And the stool frequency and stool character score of patient case 2 decreased more significantly. Intestinal microbiota also improved more significantly after the precise capsule transplantation treatment. And we found Eubacterium_ Eligens showed the same change trend in the treatment of two patients, which may play a role in the treatment. Conclusion: precision probiotic strains transplantation capsules is more beneficial to improve the intestinal microbiota of patients than microbiota transplantation capsule and live combined bacillus subtilis and enterococcus faecium capsules, so as to better alleviate clinical symptoms. This study provides a more perfect and convenient therapeutic drugs for the treatment of IBS.

Roseburia intestinalis and Its Metabolite Butyrate Inhibit Colitis and Upregulate TLR5 through the SP3 Signaling Pathway.

The pathogenesis of ulcerative colitis (UC) is unclear, but it is generally believed to be closely related to an imbalance in gut microbiota. Roseburia intestinalis (R. intestinalis) might play a key role in suppressing intestinal inflammation, but the mechanism of its anti-inflammatory effect is unknown. In this study, we investigated the role of R. intestinalis and Toll-like receptor 5 (TLR5) in relieving mouse colitis. We found that R. intestinalis significantly upregulated the transcription of TLR5 in intestinal epithelial cells (IECs) and improved colonic inflammation in a colitis mouse model. The flagellin of R. intestinalis activated the release of anti-inflammatory factors (IL-10, TGF-ß) and reduced inflammation in IECs. Furthermore, butyrate, the main metabolic product secreted by R. intestinalis, regulated the expression of TLR5 in IECs. Our data show that butyrate increased the binding of the transcription factor Sp3 (specificity protein 3) to the TLR5 promoter regions, upregulating TLR5 transcription. This work provides new insight into the anti-inflammatory effects of R. intestinalis in colitis and a potential target for UC prevention and treatment.

Development and Validation of a Deep Neural Network for Accurate Identification of Endoscopic Images From Patients With Ulcerative Colitis and Crohn's Disease.

Background and Aim: The identification of ulcerative colitis (UC) and Crohn's disease (CD) is a key element interfering with therapeutic response, but it is often difficult for less experienced endoscopists to identify UC and CD. Therefore, we aimed to develop and validate a deep learning diagnostic system trained on a large number of colonoscopy images to distinguish UC and CD. Methods: This multicenter, diagnostic study was performed in 5 hospitals in China. Normal individuals and active patients with inflammatory bowel disease (IBD) were enrolled. A dataset of 1,772 participants with 49,154 colonoscopy images was obtained between January 2018 and November 2020. We developed a deep learning model based on a deep convolutional neural network (CNN) in the examination. To generalize the applicability of the deep learning model in clinical practice, we compared the deep model with 10 endoscopists and applied it in 3 hospitals across China. Results: The identification accuracy obtained by the deep model was superior to that of experienced endoscopists per patient (deep model vs. trainee endoscopist, 99.1% vs. 78.0%; deep model vs. competent endoscopist, 99.1% vs. 92.2%, P < 0.001) and per lesion (deep model vs. trainee endoscopist, 90.4% vs. 59.7%; deep model vs. competent endoscopist 90.4% vs. 69.9%, P < 0.001). In addition, the mean reading time was reduced by the deep model (deep model vs. endoscopists, 6.20 s vs. 2,425.00 s, P < 0.001). Conclusion: We developed a deep model to assist with the clinical diagnosis of IBD. This provides a diagnostic device for medical education and clinicians to improve the efficiency of diagnosis and treatment.

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology. IBS is caused by a disruption in the gut-brain axis. Given the importance of the gut microbiota in maintaining local and systemic homeostasis of immunity, endocrine, and other physiological processes, the microbiota-gut-brain axis has been proposed as a key regulator in IBS. Neurotransmitters have been shown to affect blood flow regulation, intestinal motility, nutrient absorption, the gastrointestinal immune system, and the microbiota in recent studies. It has the potential role to play a function in the pathophysiology of the gastrointestinal and neurological systems. Transmitters and their receptors, including 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and histamine, play an important role in IBS, especially in visceral sensitivity and gastrointestinal motility. Studies in this field have shed light on revealing the mechanism by which neurotransmitters act in the pathogenesis of IBS and discovering new therapeutic strategies based on traditional pharmacological approaches that target the nervous system or novel therapies that target the microbiota.

Corrigendum: Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.

[This corrects the article DOI: 10.3389/fcimb.2021.759435.].

Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.

Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).

Effect of haptoglobin on the treatment of chronic hepatitis B with interferon.

There are two main types of drugs that are used to treat chronic hepatitis B (CHB), including interferon (IFN) and nucleotide analogues. IFN inhibits the virus through direct antiviral activity and via immune regulation, and it has been widely applied for the treatment of CHB and other infections. However, the efficiency of IFN therapy is not entirely satisfactory. The aim of the present study was to investigate the factors affecting IFN therapy. The plasma of patients with CHB treated with IFN was collected and divided into the virological response group and non-virological response group according to their virological response. Serum proteins of virologically responsive patients were compared before and after IFN therapy using isobaric tags for relative and absolute quantitation technology. ELISA was used to validate these results in the same sample. In in vitro cell experiments, HepG2.2.15 cells were transfected with haptoglobin (Hp)-targeting small interfering RNA to inhibit expression of the Hp protein, and reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to detect hepatitis B virus (HBV)-DNA, IFN and downstream molecular changes in the cell supernatants. The Hp protein levels were demonstrated to be significantly lower following 48 weeks of IFN therapy, and the levels of Hp in patients in the virological response group were significantly lower than those in the non-virological response group. In in vitro cell experiments, following inhibition of Hp protein expression, significantly decreased levels of HBV-DNA, and elevated levels of IFN and its downstream molecules were observed. These findings suggest that Hp may be able to predict the efficacy of IFN therapy, and it may inhibit HBV clearance. There is an association between Hp and IFN, which requires further clinical and laboratory studies to explore.