Unraveling the role of the upper small intestine microbiome in metabolic diseases: insight on new potential therapeutic interventions

Eugeni Belda; Emilie Steinbach; Rohia Alili; Solia Adriouch; Davide Masi; Emavieve Colas; Charlene Dauriat; Gianfranco Donatelli; Jean-Loup Doumont; Laurent Genser; Flavien Jacques; Melissa Kordahi; Veronique Pelloux; Harry Sokol; Paul Taillandier; Thierry Tuszunski; Benoit Chassaing; Roy Tiphaine Le; Karine Clement

doi:10.1530/endoabs.99.P258

P258

Prev Next

Section Contents Cite

Endocrine Abstracts (2024) 99 P258 | DOI: 10.1530/endoabs.99.P258

ECE2024 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (130 abstracts)

Unraveling the role of the upper small intestine microbiome in metabolic diseases: insight on new potential therapeutic interventions

Eugeni Belda ¹ , Emilie Steinbach ¹ , Rohia Alili ¹ , Solia Adriouch ¹ , Davide Masi ² , Emavieve Colas ¹ , Charlène Dauriat ³ , Gianfranco Donatelli ⁴ , Jean-Loup Doumont ⁴ , Laurent Genser ¹ , Flavien Jacques ¹ , Melissa Kordahi ³ , Véronique Pelloux ¹ , Harry Sokol ⁵ , Paul Taillandier ¹ , Thierry Tuszunski ⁴ , Benoit Chassaing ³ , Tiphaine Le Roy ¹ & Karine Clément ¹

Err

Author affiliations

¹Sorbonne Université, Inserm, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, Paris, France; ²Sapienza University of Rome, Experimental Medicine, Roma, Italy; ³Université de Paris, Inserm U1016, Team ’ Mucosal microbiota in chronic inflammatory diseases’, Cnrs Umr 8104, Paris, France; ⁴Hôpital privédes Peupliers - Ramsay Générale de Santé, Paris, France; ⁵Sorbonne Université, Inserm Umrs-938, Centre de Recherche Saint-Antoine, Crsa, AP-HP, Paris, France; Paris Center for Microbiome Medicine, Fédération Hospitalo-Universitaire, Paris, France; INRAE, UMR1319 Micalis & AgroParisTech, Jouy en Josas, France

Introduction: While extensive research on the fecal microbiome (FM) has already underscored the gut microbiome’s role in metabolic diseases, it is imperative to recognize its limitations in depicting the entire gastrointestinal tract. Each segment of the tract harbors unique conditions shaping microbial ecosystems, necessitating exploration beyond the FM. The upper small intestine (USI) significantly impacts nutrient digestion and absorption, hinting at its microbiome’s potential influence on the regulation of host metabolism. In a recent systematic review of the literature, we pointed out that studies on the C57BL/6 murine strain fed a high-fat diet showed a causal connection between the USI microbiome (USIM) and metabolism. However, research on individuals with obesity remains scarce and conflicting, and comparative studies between different gastrointestinal niches in patients with obesity are lacking.

Materials and Methods: This pilot study employed Shotgun Illumina sequencing to conduct metagenomic analysis of the USI, FM, and oral microbiome (OM) in both candidates for metabolic surgery (n=15) and healthy controls (n=15).

Results: USIM exhibited lower gene richness than OM and FM (P<0.0001). Compositionally, USIM resembled OM more than FM but exhibited significant differences from FM. Multivariate permutational analysis revealed that body composition and corpulence variables accounted for variance in USIM and its associated metabolome composition, showing a negative correlation with metagenomic richness. Comparison between groups with and without obesity within each ecosystem unveiled greater metagenomic richness in the USI of patients with obesity (P=0.037). This group also displayed a lower relative abundance of Proteobacteria (P<0.001), notably Neisseriaceae (P<0.0001), in the USIM.

Conclusion: Our study underscores the significance of studying the proximal gut microbiota to unravel intricate connections between gut microbiota composition and metabolic health. These insights provide a foundation for potential therapeutic interventions targeting the proximal gut microbiome in managing metabolic diseases.