Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.

Effects of Bacterial Metabolites on the Immune System: Enemies and Friends

: Metabolites produced by bacteria can influence the immune system. These metabolites are produced by pathogenic bacteria as well as the friendly microbiota. This review sheds light on the major bacterial metabolites and their structures. It also describes the capacity of these molecules to stimulate and inhibit the immune responses in a way that affects their capacity to control different diseases.

Gut bacterial metabolites modulate endoplasmic reticulum stress

Background The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with inflammatory bowel disease (IBD), a chronic condition characterized by changes to the mucosa and alteration of the gut microbiota. While the microbiota and microbially derived metabolites have also been implicated in ER stress, examples of this connection remain limited to a few observations from pathogenic bacteria. Furthermore, the mechanisms underlying the effects of bacterial metabolites on ER stress signaling have not been well established. Results Utilizing an XBP1s-GFP knock-in reporter colorectal epithelial cell line, we screened 399 microbiome-related metabolites for ER stress pathway modulation. We find both ER stress response inducers (acylated dipeptide aldehydes and bisindole methane derivatives) and suppressors (soraphen A) and characterize their activities on ER stress gene transcription and translation. We further demonstrate that these molecules modulate the ER stress pathway through protease inhibition or lipid metabolism interference. Conclusions Our study identified novel links between classes of gut microbe-derived metabolites and the ER stress response, suggesting the potential for these metabolites to contribute to gut ER homeostasis and providing insight into the molecular mechanisms by which gut microbes impact intestinal epithelial cell homeostasis.

Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis

Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19

The gut microbiota is well known to exert multiple benefits on human health including protection from disease causing pathobiont microbes. It has been recognized that healthy intestinal microbiota is of great importance in the pathogenesis of COVID-19. Gut dysbiosis caused by various reasons is associated with severe COVID-19. Therefore, the modulation of gut microbiota and supplementation of commensal bacterial metabolites could reduce the severity of COVID-19. Many approaches have been studied to improve gut microbiota in COVID-19 including probiotics, bacterial metabolites, and prebiotics, as well as nutraceuticals and trace elements. So far, 19 clinical trials for testing the efficacy of probiotics and synbiotics in COVID-19 prevention and treatment are ongoing. In this narrative review, we summarize the effects of various approaches on the prevention and treatment of COVID-19 and discuss associated mechanisms.