Discovery of bioactive microbial gene products in inflammatory bowel disease

Zhang, Yancong; Bhosle, Amrisha; Bae, Sena; McIver, Lauren J.; Pishchany, Gleb; Accorsi, Emma K.; Thompson, Kelsey N.; Arze, Cesar; Wang, Ya; Subramanian, Ayshwarya; Kearney, Sean M.; Pawluk, April; Plichta, Damian R.; Rahnavard, Ali; Shafquat, Afrah; Xavier, Ramnik J.; Vlamakis, Hera; Garrett, Wendy S.; Krueger, Andy; Huttenhower, Curtis; Franzosa, Eric A.

doi:10.1038/s41586-022-04648-7

Cited by 54 publications

(38 citation statements)

References 46 publications

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“…For example, a salt-enriched diet has been linked to a particular protein expression panel secreted by bacteria. 58 Indeed, recent evidence indicates that IBD is associated with a distinct profile of well-characterised and un-characterised bacterial proteins, 59 and-in case of pathogens-microbes use complex secretion systems to deliver virulence proteins to disrupt cellular functions of the host. 60 61 The diet is thought to strongly contribute to microbial variation in mice (~50%) and humans ~20%, with strong differences between individuals.…”

Section: Box 1 Nutrients Fuelling Gut Inflammationmentioning

confidence: 99%

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Adolph

Zhang

2022

Gut

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The diet and gut microbiota have been extensively interrogated as a fuel for gut inflammation in inflammatory bowel diseases (IBDs) in the last few years. Here, we review how specific nutrients, typically enriched in a Western diet, instigate or deteriorate experimental gut inflammation in a genetically susceptible host and we discuss microbiota-dependent and independent mechanisms. We depict the study landscape of nutritional trials in paediatric and adult IBD and delineate common grounds for dietary advice. Conclusively, the diet reflects a critical rheostat of microbial dysbiosis and gut inflammation in IBD. Dietary restriction by exclusive enteral nutrition, with or without a specific exclusion diet, is effectively treating paediatric Crohn's disease, while adult IBD trials are less conclusive. Insights into molecular mechanisms of nutritional therapy will change the perception of IBD and will allow us to enter the era of precision nutrition. To achieve this, we discuss the need for carefully designed nutritional trials with scientific rigour comparable to medical trials, which also requires action from stake holders. Establishing evidencebased dietary therapy for IBD does not only hold promise to avoid long-term immunosuppression, but to provide a widely accessible therapy at low cost. Identification of dietary culprits disturbing gut health also bears the potential to prevent IBD and allows informed decision making in food politics.

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Section: Box 1 Nutrients Fuelling Gut Inflammationmentioning

confidence: 99%

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Adolph

Zhang

2022

Gut

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“…Meanwhile, a network of bacteria-metabolite interactions has shown some mechanisms linked to disease activity in Crohn’s disease [ 21 ]. Thousands of candidate microbial proteins are likely to interact with the host immune system in IBD [ 22 ]. Researchers have found that MSC therapy may be associated with the gut microbiota in many diseases, including ulcerative colitis [ 23 ], acute liver injury [ 24 ], hypoxia-induced pulmonary hypertension [ 25 ], chronic hypoxia [ 26 ], and diabetes [ 27 ], which leads to gut dysbiosis.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

Yang

Liu

et al. 2022

Stem Cell Res Ther

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Background Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. Methods We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. Results MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α-diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group Conclusions Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD.

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“…Several studies have also demonstrated that IBD is closely related to the gut microbial community dysbiosis [ 22 – 25 ]. Thus, gut microbial metaproteome analysis has also been applied to IBD prevention and therapeutic target discovery [ 26 , 27 ]. Nevertheless, to the best of our knowledge, investigations regarding overweight/obesity influencing IBD using proteomic and metaproteomic applications are very limited.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Discovery of bioactive microbial gene products in inflammatory bowel disease

Cited by 54 publications

References 46 publications

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Human umbilical cord-derived mesenchymal stem cells ameliorate experimental colitis by normalizing the gut microbiota

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

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