Integrating the serum proteomic and fecal metaproteomic to analyze the impacts of overweight/obesity on IBD: a pilot investigation

Abstract

Background Inflammatory bowel disease (IBD) encompasses a group of chronic relapsing disorders which include ulcerative colitis (UC) and Crohn’s disease (CD). The incidences of IBD and overweight/obesity are increasing in parallel. Here, we investigated alterations in proteomic in serum and metaproteomic in feces of IBD patients with overweight/obesity and aimed to explore the effect of overweight/ obesity on IBD and the underlying mechanism. Methods This prospective observational study (n = 64) comprised 26 health control subjects (HC, 13 with overweight/obesity) and 38 IBD patients (19 with overweight/obesity) at a tertiary hospital. Overweight/obesity was evaluated by body mass index (BMI) and defined as a BMI greater than 24 kg/m2. The comprehensive serum proteomic and fecal metaproteomic analyses were conducted by ultra-performance liquid chromatography-Orbitrap Exploris 480 mass spectrometry. Results UC and CD presented similar serum molecular profiles but distinct gut microbiota. UC and CD serum exhibited higher levels of cytoskeleton organization- associated and inflammatory response-related proteins than the HC serum. Compared the serum proteome of UC and CD without overweight/obesity, inflammatory response-associated proteins were dramatically decreased in UC and CD with overweight/obesity. Fecal metaproteome identified 66 species in the feces. Among them, Parasutterella excrementihominis was increased in CD compared with that in HC. UC group had a significant enrichment of Moniliophthora roreri, but had dramatically decreased abundances of Alistipes indistinctus, Clostridium methylpentosum, Bacteroides vulgatus, and Schizochytrium aggregatum. In addition, overweight/obesity could improve the microbial diversity of UC. Specifically, the UC patients with overweight/obesity had increased abundance of some probiotics in contrast to those without overweight/obesity, including Parabacteroides distasonis, Alistipes indistincus, and Ruminococcus bromii. Conclusion This study provided high-quality multi-omics data of IBD serum and fecal samples, which enabled deciphering the molecular bases of clinical phenotypes of IBD, revealing the impacts of microbiota on IBD, and emphasizing the important role of overweight/obesity in IBD.

The Peptonizer2000: graphical model based taxonomic identifications of metaproteomic samples

“…This type of cut-off is very common in metaprotoemic workflows. [18][19][20]41,42 The Peptonizer results attribute all highest scores to the correct taxa. Since they represent a probability distribution, introducing a 'cut-off' probability for present taxa does not make sense mathematically, but will often be necessary for practical reasons.…”

Weight Loss Promotion in Individuals with Obesity through Gut Microbiota Alterations with a Multiphase Modified Ketogenic Diet

“…Among the above characteristics, the relative abundance of P. distasonis, the most critical microbial feature, increased significantly after the intervention. Previous studies have identified a decrease in the abundance of P. distasonis in obese and metabolic syndrome populations [37,38]. Additionally, other studies of dietary interventions for treating obesity have shown an upward trend in the relative abundance of P. distasonis after the intervention.…”

Reviewing the impact of obesity on inflammatory bowel disease and considerations for optimizing management

“…Numerous studies have established the presence of dysbiosis in individuals with IBD, demonstrating reduced bacterial diversity particularly during flares, and the possibility of normalization of bacterial microbiota after long periods of remission [11]. A recent study integrated serum proteomic and fecal metaproteomic analyses to examine the effect of overweight and obesity on these profiles in IBD, demonstrating that ulcerative colitis and Crohn's disease displayed similar serum molecular profiles in the setting of overweight or obesity, but that the presence of overweight/obesity disparately impacted gut microbiota composition in ulcerative colitis vs. Crohn's disease [12 ▪ ]. Interestingly, overweight/obesity appeared to enhance microbial diversity in ulcerative colitis, particularly increasing the abundance of certain organisms with the potential to serve as probiotics (e.g., Parabacteroides distasonis , Alistipes indistincus , and Ruminococcus bromii) .…”

“…It is not known whether this suggests overweight/obesity may portend a protective microbial environment in ulcerative colitis, or if rather overweight/obesity status indicates a less severe disease course of their ulcerative colitis. Comprehensive multiomics studies such as these are helpful to shed light on the molecular underpinnings of IBD, the influence of microbiota, and the added impact of overweight/obesity [12 ▪ ].…”