The clinical spectra of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) intersect to form a scantily defined overlap syndrome, termed pre-IBD. We show that increased Enterobacteriaceae and reduced Clostridia abundance distinguish the fecal microbiota of pre-IBD patients from IBS patients. A history of antibiotics in individuals consuming a high-fat diet was associated with the greatest risk for pre-IBD. Exposing mice to these risk factors resulted in conditions resembling pre-IBD and impaired mitochondrial bioenergetics in the colonic epithelium, which triggered dysbiosis. Restoring mitochondrial bioenergetics in the colonic epithelium with 5-amino salicylic acid, a PPAR-g (peroxisome proliferator-activated receptor gamma) agonist that stimulates mitochondrial activity, ameliorated pre-IBD symptoms. As with patients, mice with pre-IBD exhibited notable expansions of Enterobacteriaceae that exacerbated low-grade mucosal inflammation, suggesting that remediating dysbiosis can alleviate inflammation. Thus, environmental risk factors cooperate to impair epithelial mitochondrial bioenergetics, thereby triggering microbiota disruptions that exacerbate inflammation and distinguish pre-IBD from IBS.

Lactobacillus provides many health benefits; its various species are widely used as probiotics. However, an increased abundance of Lactobacillus has been reported in obesity, and the role of Lactobacillus strains in obesity remains unknown.

Abstract Background: Obesity is one of the major public health problems related to various chronic health conditions, with steadily increasing prevalence worldwide. Lactobacillus provides various benefits to the host body; however, its role in obesity is unknown. Results: In this study, we found higher colonisation of Lactobacillus sakei species in obesity group, which in turn was related to increased reactive oxygen species (ROS) levels induced by higher fat intake. We isolated L. sakei ob4.1 strain from the faeces of one subject with obesity and compared its genetic and molecular features with those of L. sakei DSM 20017 strain. L. sakei ob4.1 showed higher catalase activity, which was regulated by oxidative stress at gene transcriptional levels. L. sakei ob4.1 maintained colon epithelial cell-adhesion ability under ROS stimulation, and live bacteria could decrease colon epithelial inflammation in a dose-dependent manner. Establishing a mouse model revealed high-fat diet-induced colon ROS to be associated with increased colonisation of L. sakei ob4.1 through catalase activity. Four-week supplementation with this strain could reduce colon inflammation effectively, though not so for body weight or ROS levels in high fat-fed mice. Conclusion: We, therefore, concluded that changes in host gut-oxidative stress levels could link high fat-induced obesity to increased colonisation of L. sakei ob4.1 , and this strain could be potent as anti-inflammatory probiotic in obese population with gut inflammation. Keywords Lactobacillus sakei; Obesity; Gut microbiome; Reactive oxygen stress; Inflammation; High fat diet