Clostridium butyricum regulates visceral hypersensitivity of irritable bowel syndrome by inhibiting colonic mucous low grade inflammation through its action on NLRP6.

Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1ß, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18 and IL-1ß were also increased after the NLRP6 gene was silenced. Pathological score suggested low inflammation of colonic mucous rather than terminal ileum. Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic distension. However, treatment with Clostridium butyricum reversed these results, exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.

Long-term gastrointestinal symptoms and sleep quality sequelae in adolescents after COVID-19: a retrospective study.

Objective: To evaluate the long-term gastrointestinal (GI) symptoms and sleep quality sequelae in adolescents with COVID-19. Methods: Between June and July 2023, an online survey was done in Xiaoshan District, Hangzhou City, Zhejiang Province, China, using the GI Symptom Rating Scale (GSRS) and the Pittsburgh Sleep Quality Inventory (PSQI). Results: GI symptoms in COVID-19 patients increased by 11.86% compared to before infection, while sleep quality decreased by 10.9%. Over time, there was a significant increase in the cumulative incidence rate of GI symptoms and sleep disorders (p < 0.001). Follow-up of COVID-19 positive patients within 6 months of infection showed that GI symptoms and sleep quality began to ease starting from the first month after infection. Further analysis indicated a significant linear relationship between the severity of GI symptoms and sleep quality (R > 0.5, p < 0.001). Moreover, females, older age, and higher education were identified as risk factors influencing the long-term effects of COVID-19. Conclusion: SARS-CoV-2 affects GI symptoms and sleep quality in adolescents during both the acute phase and post-infection periods. Over time, these symptoms gradually alleviate. A significant correlation exists between GI symptoms and sleep quality.

Clinically significant endoscopic findings in patients of dyspepsia with no warning symptoms: A cross-sectional study.

BACKGROUND: Dyspepsia is one of the commonest clinical disorder. However, controversy remains over the role of endoscopy in patients with dyspepsia. No studies have evaluated the diagnostic value of endoscopy in patients with no warning symptoms according to the Rome IV criteria. AIM: To study the diagnostic value of endoscopy in dyspeptic patients with no warning symptoms. METHODS: This cross-sectional study included dyspeptic patients with no warning symptoms who met the inclusion and exclusion criteria at The First Affiliated Hospital, Zhejiang Chinese Medical University from April 2018 to February 2019. The clinical data were collected using questionnaires, including dyspeptic information, warning symptoms, other diseases, family history and basic demographic data. Based on dyspeptic symptoms, patients can be divided into epigastric pain syndrome, postprandial distress syndrome or overlapping subtypes. RESULTS: A total of 1016 cases were enrolled, 304 (29.9%) had clinically significant findings that were detectable by endoscopy. The endoscopy findings included esophageal lesions in 180 (17.7%) cases, peptic ulcers in 115 (11.3%) cases and malignancy in 9 (0.89%) patients. Multivariate logistic regression analysis showed that males [odds ratio (OR) = 1.758, P < 0.001], body mass index > 25 (OR = 1.660; P = 0.005), epigastric pain (OR = 1.423; P = 0.019) and Helicobacter pylori infection (OR = 1.949; P < 0.001) were independently associated with risk factors for the presence of clinically significant findings on endoscopy. CONCLUSION: Chinese patients with dyspepsia with no warning symptoms should undergo endoscopy, particularly males, patients with body mass index > 25, epigastric pain or Helicobacter pylori infection.

Impact of Helicobacter pylori eradication on the gastric microbiome.

BACKGROUND: Helicobacter pylori (Hp) eradication has been used for many years. Yet, the impact of this eradication on the normal gastric microflora is not well understood. In this study, we explored the effect of eradication on the stomach microbial community and its recovery after successful Hp eradication. METHODS: Among the 89 included patients, 23, 17, 40, and 9 were included in the Hp-negative, Hp-positive, successful eradication, and failed eradication groups, respectively. Four subgroups were further determined according to disease status (Hp-negative chronic gastritis [N-CG], Hp-negative atrophic gastritis [N-AG], successful-eradication chronic gastritis [SE-CG], and atrophic gastritis with successful eradication [SE-AG]). During the endoscopic examination, one piece of gastric mucosa tissue was obtained from the lesser curvature side of the gastric antrum and gastric corpus, respectively. In addition, 16S rDNA gene sequencing was used to analyze the gastric mucosal microbiome. RESULTS: In the Hp-negative group, the gastric microbiota was dominated by five phyla: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteria. After successfully eradicating Hp, the bacterial flora in the stomach recovered to a considerable extent. In the failed eradication group, the flora was similar to the flora in Hp-positive subjects based on the alpha and beta diversities. Among the groups, Curvibacter and Acinetobacter were enriched in the presence of Hp (i.e., failed eradication and Hp-positive groups), suggesting that these two genera could be used as biomarkers in the symbiotic flora in the presence of Hp. SE-CG was characterized by an increase in Firmicutes taxa and a decrease in Proteobacteria taxa compared with N-CG. SE-AG was characterized by a decrease in Firmicutes relative to N-AG. Finally, no differences were found in the pairwise comparisons of nitrate and nitrite reductase functions of the microflora among the four subgroups. CONCLUSIONS: After Hp infection, the diversity and relative abundance of gastric microflora were significantly decreased. Yet, gastric microbiota could be partially restored to the Hp-negative status after eradication. Still, this effect was incomplete and might contribute to the long-term risks.

Alleviation of CCl4-induced cirrhosis in rats by tetramethylpyrazine is associated with downregulation of leptin and TGF-beta1 pathway.

This study was conducted to investigate the effect of tetramethylpyrazine (TMP) on CCl(4)-induced fibrosis in rats and the possible roles of leptin, TGF-beta1, Smad3, and Smad7 in this process. Liver fibrosis in rats was induced by the subcutaneous injection of 60% CCl(4) (0.3 mL /100 g body weight, biweekly ) for 12 weeks. Rats in TMP prevention and treatment groups were given TMP (10 mg /100 g body weight, daily) by gavage from days 1 and 31 after the start of CCl(4) injection, respectively. The mRNA expression of leptin, OB-Rb, TGF-beta1, and TGF-beta RII in the liver were detected by RT-PCR, whereas Smad3 and Smad7 protein were determined by Western blot. The results showed that hepatic cirrhosis was obviously alleviated in both TMP prevention and treatment groups. The mRNA expression of leptin, OB-Rb, TGF-beta1 and -beta RII, and Smad3 protein were higher in the cirrhotic models. In TMP prevention and treatment groups, these markers of expression were higher, compared with that of the normal control, but were lower when compared with that of the cirrhotic model group. Smad7 protein expression was lower in the cirrhotic model group than in the normal control. Smad7 expression in TMP prevention and treatment groups was higher, compared with that in the cirrhotic model group. Liver collagen in the TMP prevention group was the lowest among all CCl(4) injection groups. In conclusion, TMP can prevent and alleviate the development of liver fibrosis in rats. The possible mechanism could involve the downregulation of leptin, Ob-Rb, TGF-beta1, TGF-beta RII, and Samd3, and upregulation of Smad7.

[Effect of non-steroidal anti-inflammatory drugs on small intestinal barrier function in rats].

OBJECTIVE: To approach the effect on mechanical barricade of the mucous membrane of small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Thirty-two male SD rats were randomly divided into control group and model group. The rats of the model group were given 7.5 mg/kg diclofenac by gavage, bid; the rats of the control group were given the same dose of saline. Then they were further randomly divided into two subgroups (n=8) at the first day and the fifth day after making the models to observe the scores of anatomical lesion on stomach and small intestine and the scores of tissue damage of mucous membrane and to quantitatively analyze the height of villi, as well as the thickness and the section area of mucous membrane with Carl Zeiss Imaging Systems. Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission electron microscope. RESULTS: The mucous membrane of stomach of the model groups was slightly edematous. There was no difference between the scores of the model groups and control groups. It was seen that the mucous membrane of small intestine of the first day model group presented with erythema, amaurosis and ulcer. The ulcer was distributed along mesentery. The mucous membrane of small intestine of the fifth day model group showed bleeding, perforation and sinus tract formation, and the scores of anatomical lesion was higher than that of the control group (P < 0.05). The scores of the lesions of the first and fifth day model groups were 3.5 and 5.0. The difference had statistical significance when compared with those of the control groups (the scores were 0) (P < 0.05). Cell degeneration and cellular necrosis of epithelial mucosa of small intestine was also seen in the first day model group. The top of villi was ablated. The height of the pile on jejunum was (126.9 +/- 32.0) microm and that on ileum was (118.6 +/- 22.9) microm. They were lower than those of the control group (P < 0.05). However there was no difference of the thickness and section area between them, but the thickness and section area showed a tendency of decrease. It was also seen that there were apomorphosis and sphacelism of epithelial cells in the fifth day model group. Some villi were ablated and laminae propria exposed. The height of villi on jejunum [(73.4 +/- 25.4) microm] and that on ileum [(109.3 +/- 17.6) microm] decreased significantly. The thickness of mucous membrane [(123.8 +/- 51.6) microm and (165.7 +/- 37.4) microm] decreased and the section area [(2.48 +/- 1.01) mm2 and (3.27 +/- 0.76) mm2] became smaller (P < 0.05 vs. control group). The mucous membrane of the villi on small intestine was continuous but arranged disorderly. Cytochondriome swelled, endocytoplasmic reticulin expanded with different degrees, intercellular junction widened partly. The microvilli in the fifth day model group were ablated more obviously and intercellular junctions were broken and destroyed gravely. CONCLUSIONS: Diclofenac can cause damage to the function of mucous membrane barricade of small intestine. It could also lead to shortening of the villi, thinning of the mucous membrane, ablation of the microvilli, and widening of the tight intercellular junction as the characteristic morphological change.

Use of NSAIDs via the Rectal Route for the Prevention of Pancreatitis after ERCP in All-Risk Patients: An Updated Meta-Analysis.

The aim of this study was to assess the efficacy of the rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-ERCP pancreatitis (PEP). We searched database for randomized controlled trials (RCTs) comparing periprocedural rectal administration of NSAIDs with placebo for the prevention of PEP. The rectal administration of NSAIDs significantly decreased the incidence of PEP in the whole patient population (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.30-0.64, P < 0.0001), high-risk patients (OR: 0.34, 95% CI: 0.19-0.58, P = 0.0001), and all-risk patients (OR: 0.51, 95% CI: 0.31-0.84, P = 0.008). The incidence of PEP was reduced by indomethacin (OR: 0.54, 95% CI: 0.36-0.82, P = 0.004) and diclofenac (OR: 0.27, 95% CI: 0.15-0.46, P < 0.00001). The administration of NSAIDs before (OR: 0.42, 95% CI: 0.25-0.73, P = 0.002) or after (OR: 0.39, 95% CI: 0.27-0.56, P < 0.00001) ERCP reduced PEP. The NSAIDs were associated with a reduction in mild PEP (OR: 0.55, 95% CI: 0.36-0.83, P = 0.004) and moderate-to-severe PEP (OR: 0.47, 95% CI: 0.28-0.79, P = 0.004). The rectal administration of NSAIDs reduced the incidence of PEP in high-risk and all-risk patients.

Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome.

AIM: To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS: In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress (WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry (GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS: WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS (days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A (CoA) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways. CONCLUSION: The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism.