Appendiceal microbiome in uncomplicated and complicated acute appendicitis: A prospective cohort study

Uncomplicated and complicated acute appendicitis seem to be two different forms of this common abdominal emergency. The contribution of appendiceal microbiota to appendicitis pathogenesis has been suggested, but differences between uncomplicated and complicated appendicitis are largely unknown. We compared the appendiceal microbiota in uncomplicated and complicated acute appendicitis.\nThis prospective single-center clinical cohort study was conducted as part of larger multicenter MAPPAC trial enrolling adult patients with computed tomography or clinically confirmed uncomplicated or complicated acute appendicitis. The microbial composition of the appendiceal lumen was determined using 16S rRNA gene amplicon sequencing.\nBetween April 11, 2017, and March 29, 2019, 118 samples (41 uncomplicated and 77 complicated appendicitis) were available. After adjusting for age, sex, and BMI, alpha diversity in complicated appendicitis was higher (Shannon p = 0.011, Chao1 p = 0.006) compared to uncomplicated appendicitis. Microbial compositions were different between uncomplicated and complicated appendicitis (Bray-Curtis distance, P = 0.002). Species poor appendiceal microbiota composition with specific predominant bacteria was present in some patients regardless of appendicitis severity.\nUncomplicated and complicated acute appendicitis have different appendiceal microbiome profiles further supporting the disconnection between these two different forms of acute appendicitis.\nClinicalTrials.gov NCT03257423.</p

Do the secreted molecules of gut bacterium Faecalibacterium prausnitzii inhibit the fat accumulation in hepatocytes in vitro?

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder in which fat accumulates in liver without excessive alcohol use. NAFLD is a disease in which distortions in gut microbiota seems to play an important role. In previous studies this research group has discovered that the abundance of gut bacterium Faecalibacterium prausnitzii is lower in individuals with high hepatic fat content. In healthy human gut F. prausnitzii is one of the most abundant bacterial species. The main aim for this project was to find out does the growth media of F. prausnitzii possess beneficial effects on hepatocytes in vitro. This work also surveyed dietary fibers that could stimulate the growth of F. prausnitzii. As a model for fatty liver, human hepatocyte-derived cell line HepG2 was used and the fat accumulation was induced with the mix of oleic-palmitic acid. The growth media supernatant of F. prausnitzii was applied on the HepG2 cells together with oleic-palmitic acid mix. To quantify the amount of intracellular fat, Oil Red O staining was used. F. prausnitzii (ATCC27766) was cultured in anaerobic chambers. The effects of various fibers were studied by following changes in optical density at 600 nm. The growth media supernatant of F. prausnitzii did not inhibit the HepG2 fat accumulation in vitro. This indicates that the positive effects of F. prausnitzii on liver are not necessarily directly mediated. However, to confirm this, the method requires further optimization. We were able to identify a fiber that clearly stimulates the growth of F. prausnitzii. This fiber can be possibly used to increase the abundance of F. prausnitzii in the gut.Siirretty Doriast

Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings

Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity, while in older adult (hereafter old) rats most of the differences between the lines associated with body weight. Despite the absence of weight differential between LCR and HCR when young, the LCR microbiome contained more Actinobacteria, Veillonellaceae, Coriobacteriaceae, Phascolarctobacterium, and Ruminococcus; taxa previously linked to obesity. This raises the question whether the microbiome contributes to the later development of obesity in LCR. Age-related differences were detected in almost all taxa in both rat lines. The young HCR measured higher for serum glycerol and free fatty-acids and lower for cholesterol, HDL, LDL, and triglycerides than LCR. The old HCR differed from the old LCR by lower LDL. Several metabolites, including LDL, are associated age and genetic background-dependently with the microbiome, which might explain the metabolic differences between the lines. While old lines did not differ in visceral adipose tissue gene expression, the young HCR expressed more inflammatory genes than LCR, and several taxa including Proteobacteria associated with these genes. In conclusion, intrinsic aerobic capacity governs the microbiome, which may influence body weight, metabolism, and gene expression.peerReviewe

Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.peerReviewe