Comparative Analysis of the Duodenojejunal Microbiome with the oral and fecal microbiome unveils its role in Human Severe Obesity

The intestinal microbiota is recognized as an important player in the development and maintenance of obesity. Most studies focus on faecal microbiota because of its accessibility. However, the small intestine is a major site for nutrient sensing and absorption and few studies have examined the composition and function of the microbiota in this segment of the digestive tract. We conducted a clinical research project on 30 age- and sex-matched participants with (N=15) and without (N=15) obesity. Duodenojejunal fluid was obtained by aspiration during fibroscopy. Phenotyping included clinical variables related to metabolic status, lifestyle and psychosocial factors using validated questionnaires. Metagenomic analyses of the oral, duodenojejunal and faecal microbiome, as well as metabolomic data from duodenojejunal fluid and faeces, were integrated with clinical and lifestyle data. The results show associations between duodenojejunal microbiota and lifestyle as well as clinical phenotypes. These associations had larger effect sizes than the associations between these variables and faecal microbiota. We also observed that the duodenojejunal microbiota of obese patients had a higher diversity. In addition, we observed differences in the abundance of several species of the duodenojejunal microbiota between control individuals and patients suffering from obesity. In conclusion, our results support the relevance of studying the role of the small intestinal microbiota in the development of metabolic diseases. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study received the following grants: Fondation de l'Avenir (AP-RM-20-015 and AP-RM-21-032), INSERM, Societe Francophone du Diabete, Leducq foundation, FHU PaCeMM, a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. ERC-2018-StG- 804135), ANR grants EMULBIONT (ANR-21-CE15-0042-01) and DREAM (ANR-20-PAMR-0002). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study adhered to the Helsinki Declaration and ethics committee 'Comite de protection des personnes Ile de France VIII' (CPP Ile de France 8; approval number: 210648) of Institut National de la Sante Et de la Recherche Medicale gave approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. Metagenomics sequencing reads are available on European Nucleotide Archive under Project PRJEB69217.