Causal relationship between gut microbiota and constipation: a bidirectional Mendelian randomization study.

Background: Constipation is a prevalent gastrointestinal disorder affecting approximately 15% of the global population, leading to significant healthcare burdens. Emerging evidence suggests that gut microbiota plays a pivotal role in the pathogenesis of constipation, although causality remains uncertain due to potential confounding factors in observational studies. This study aims to clarify the causal relationships between gut microbiota and constipation using a bidirectional Mendelian Randomization (MR) approach, which helps to overcome confounding issues and reverse causality. Methods: Utilizing data from genome-wide association studies (GWAS) from the MiBioGen consortium and other sources, we identified genetic variants as instrumental variables (IVs) for 196 bacterial traits and constipation. These IVs were rigorously selected based on their association with the traits and absence of linkage with confounding factors. We applied several MR methods, including Inverse Variance Weighted (IVW), MR Egger, and MR-PRESSO, to examine the causal effects in both directions. Results: Our analysis revealed a significant causal relationship where specific bacterial taxa such as Coprococcus1 (OR = 0.798, 95%CI: 0.711-0.896, p < 0.001), Coprococcus3 (OR = 0.851, 95%CI: 0.740-0.979, p = 0.024), Desulfovibrio (OR = 0.902, 95%CI: 0.817-0.996, p = 0.041), Flavonifractor (OR = 0.823, 95%CI: 0.708-0.957, p < 0.001), and Lachnospiraceae UCG004, whereas others including Ruminococcaceae UCG005 (OR = 1.127, 95%CI: 1.008-1.261, p = 0.036), Eubacterium nodatum group (OR = 1.080, 95%CI: 1.018-1.145, p = 0.025), Butyricimonas (OR = 1.118, 95%CI: 1.014-1.233, p = 0.002), and Bacteroidetes (OR = 1.274, 95%CI: 1.014-1.233, p < 0.001) increase constipation risk. In the reverse MR analysis, constipation was found to influence the abundance of certain taxa, including Family XIII, Porphyromonadaceae, Proteobacteria, Lentisphaeria, Veillonellaceae, Victivallaceae, Catenibacterium, Sellimonas, and Victivallales, indicating a bidirectional relationship. Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conclusion: The relationship between our study gut microbiota and constipation interacts at the genetic level, which gut microbiota can influence the onset of constipation, and constipation can alter the gut microbiota. Coprococcus1, Coprococcus3, Desulfovibrio, Flavonifractor and Lachnospiraceae UCG004 play a protective role against constipation, while Ruminococcaceae UCG005, Eubacterium nodatum group, Butyricimonas, and Bacteroidetes are associated with an increased risk. In addition, constipation correlates positively with the abundance of Family XIII, Porphyromonadaceae and Proteobacteria, while negatively with Lentisphaeria, Veillonellaceae, Victivallaceae, Catenibacterium, Sellimonas, and Victivallales.

The improvement of Hovenia acerba-sorghum co-fermentation in terms of microbial diversity, functional ingredients, and volatile flavor components during Baijiu fermentation.

The quality of Baijiu was largely affected by raw materials, which determine the flavor and taste. In the present study, organic acids, polyphenols, volatile flavor components and microbial community in Hovenia acerba-sorghum co-fermented Baijiu (JP1) and pure sorghum-fermented Baijiu (JP2) were comprehensively analyzed. Organic acids, polyphenols and volatile flavor components in JP1 were more abundant than JP2. The abundance and diversity of bacteria and fungi in JP1 was higher than that in JP2 in the early stage of fermentation, but presented opposite trend in the middle and late stages. Leuconostoc, Lentilactobacillus and Issatchenkia were dominant genera in JP1. Whereas, Cronobacter, Pediococcus and Saccharomyces occupied the main position in JP2. Lentilactobacillus and Issatchenkia were positively related to most of organic acids and polyphenols. Pseudomonas, Rhodococcus, Cronobacter, Pediococcus, Brucella, Lentilactobacillus, Lactobacillus, Saccharomycopsis, Wickerhamomyces, Aspergillus, Thermomyces and unclassified_f-Dipodascaccae were associated with the main volatile flavor components. The main metabolic pathways in two JPs exhibited the variation trend of first decreasing and then increasing, and the metabolism activity in JP1 were higher than that in JP2. The results demonstrated the introduction of Hovenia acerba improved the functional ingredients and volatile flavor components, which is helpful for the quality promotion of Baijiu. This study identified the key microorganisms and discussed their effect on organic acids, polyphenols and volatile flavor components during the fermentation of Baijiu with different raw materials, providing a scientific basis for the development and production of high-quality Baijiu.

miR-137 Modulates Human Gastric Cancer Cell Proliferation, Apoptosis, and Migration by Targeting EZH2.

Gastric cancer (GC) is a malignancy of the digestive tract with rapid progress, poor prognosis, and low survival rate. The aberrant expression of microRNA (miRNA) is closely related to the tumorigenesis and progression of GC. The purpose of this study was to investigate the effects of miR-137 on the proliferation, apoptosis, and migration of GC cells. Bioinformatics analysis revealed that EZH2 expression in GC based on The Cancer Genome Atlas (TCGA) dataset was dramatically increased, miR-137 expression was down-regulated, and miR-137 was remarkably negatively correlated with EZH2 in GC. Next, it was found that EZH2 expression was significantly increasing and miR-137 was significantly decreasing by quantitative polymerase chain reaction (qRT-PCR) in GC clinical specimens. In addition, miR-137 expression in GC cell lines was significantly lower than that in normal gastric parietal cells. TargetScan and star-Base were employed to predict that EZH2 was a potential target of miR-137, and subsequent luciferase reports confirmed this prediction. Western blot assay demonstrated that up-regulation of miR-137 decreased EZH2 expression in BGC-823 cells, whereas silenced miR-137 enhanced EZH2 expression in SGC-7901 cells. The gain/loss-of-function indicates that miR-137 regulates the proliferation, apoptosis, migration and epithelial-mesenchymal transition of GC cells. In conclusion, our findings indicate that miR-137 restrains migration and proliferation and induces apoptosis partially through negatively regulating the expression of EZH2 in GC cells.

De Garengeot hernia with avascular necrosis of the appendix: A case report.

BACKGROUND: An incarcerated hernia is a common cause of acute abdominal pain. There are various types of incarcerated hernias, including incarcerated hernias of the appendix. These hernias are often complicated by appendiceal inflammation, necrosis, and suppuration, which affect the outcome of surgical repair. A De Garengeot hernia is a femoral hernia that contains the appendix. This type of hernia has a low incidence. When a De Garengeot hernia is clinically suspected, emergency surgical treatment should be performed as soon as possible. CASE SUMMARY: A 59-year-old man was admitted to the hospital with a painful right inguinal mass that had suddenly developed 6 hours earlier. Physical examination revealed a 4 cm × 2 cm palpable mass in the right groin. The mass was hard and could not be reduced due to tenderness. It did not descend into the scrotum. B-ultrasound revealed an incarcerated hernia. During surgery, the hernia was found to contain the appendix, which exhibited distal avascular necrosis. A De Garengeot hernia was diagnosed according to the classification criteria of this type of inguinal hernia. Laparoscopic reduction of the incarcerated hernia, appendectomy, and small-incision femoral hernia repair were performed in the emergency department, and cefuroxime was administered as anti-infection therapy for 2 d postoperatively. After treatment, the patient had no abdominal pain or infection and was discharged on postoperative day 4. He had no recurrence of the inguinal hernia after 16 months of follow-up. CONCLUSION: De Garengeot hernias have a low incidence and are difficult to diagnose. Laparoscopy is useful for their diagnosis and treatment.