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Title: Akkermansia muciniphila abundance is lower in severe obesity but its increased level after bariatric surgery is not associated with metabolic health improvement

Author
item DAO, CARLOTA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BELDA, EUGENI - Institute Of Cardiometabolism And Nutrition
item PRIFTI, EDI - Sorbonne Universities, Paris
item EVERARD, AMANDINE - Universite Catholique
item KAYSER, BRANDON - Sorbonne Universities, Paris
item BOUILLOT, JEAN-LUC - Hospital Ambroise Paré
item CHEVALLIER, JEAN-MARC - Hospital Ambroise Paré
item PONS, NICOLAS - Université Paris-Saclay
item LE CHATELIER, EMMANUELLE - Université Paris-Saclay
item EHRLICH, DUSKO - Université Paris-Saclay
item DORE, JOEL - Université Paris-Saclay
item ARON-WISNEWSKY, JUDITH - The Pitié-Salpêtrière Hospital
item ZUCKER, JEAN-DANIEL - Sorbonne Universities, Paris
item CANI, PATRICE - Universite Catholique
item CLEMENT, KARINE - The Pitié-Salpêtrière Hospital

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/21/2019
Publication Date: 7/2/2019
Citation: Dao, C., Belda, E., Prifti, E., Everard, A., Kayser, B., Bouillot, J., Chevallier, J., Pons, N., Le Chatelier, E., Ehrlich, D., Dore, J., Aron-Wisnewsky, J., Zucker, J., Cani, P.D., Clement, K. 2019. Akkermansia muciniphila abundance is lower in severe obesity but its increased level after bariatric surgery is not associated with metabolic health improvement. American Journal of Clinical Nutrition. https://doi.org/10.1152/ajpendo.00140.2019.
DOI: https://doi.org/10.1152/ajpendo.00140.2019

Interpretive Summary: The gut bacterial species, Akkermansia muciniphila, is associated with a healthier clinical profile. In this study, we determined the association between A. muciniphila and clinical health in women with severe obesity undergoing two types bariatric surgery (BS): gastric banding (GB) or Roux-en-Y gastric bypass (RYGB). Gut microbiota and clinical outcomes were measured at 1, 3, and 12 months after BS. In addition, we compared A. muciniphila relative abundance between this group with severe obesity, and a group of adults with moderate obesity. At baseline, we found that A. muciniphila was less abundant in severe obesity than moderate obesity. However, there was no association between A. muciniphila and clinical outcomes in severe obesity, while the opposite had been previously found in moderate obesity. After BS, there was a significant increase in A. muciniphila abundance after RYGB but not GB. Finally, A. muciniphila was correlated with a healthier gut microbiota ecosystem (i.e. less gut dysbiosis markers) throughout the intervention. In conclusion, although decreased in severe obesity, abundance of A. muciniphila was not associated with clinical outcomes such as glucose homeostasis before or after BS. A certain level of A. muciniphila abundance might be required to observe a beneficial link to health. The severity of obesity and gut dysbiosis may partly explain the discrepancy with previous findings in less obese populations.

Technical Abstract: Background: The gut bacterial species, Akkermansia muciniphila, has been associated with metabolic health in humans and rodents. Previously we showed that higher A. muciniphila abundance is associated with better metabolic outcomes after a calorie restriction intervention. Objective: To determine the association between A. muciniphila abundance and markers of glucose homeostasis in patients undergoing bariatric surgery (BS): gastric banding (GB) or Roux7-en-Y gastric bypass (RYGB). Design: This was a non-randomized prospective study. Participants were severely obese women (N=65 at baseline) who underwent either GB (N=10) or RYGB (N=11). Blood and fecal samples were collected at baseline, 1, 3, and 12 months. Glucose homeostasis markers were measured under fasting conditions or during an oral glucose tolerance test. Gut microbiota was analyzed using shotgun metagenomics, and A. muciniphila abundance was also assessed with 16S rRNA qPCR. The association between A. muciniphila, clinical outcomes and gut microbiome composition were studied. Results: A. muciniphila abundance was significantly lower in severe obesity than overweight and moderate obesity and was not associated with markers of glucose homeostasis at baseline. There was a significant increase in A. muciniphila abundance after RYGB, but it was not correlated with post-RYGB metabolic improvement. Baseline A. muciniphila abundance was correlated with bacterial gene richness and was highest in the high-richness Ruminococcaceae enterotype. A. muciniphila increased in abundance after BS in patients with low baseline A. muciniphila, especially those with a Bacteroides 2 enterotype classification. Conclusions: Although decreased in severe obesity, A. muciniphila was not associated with clinical outcomes. A certain level of A. muciniphila abundance might be required to observe a 6 beneficial link to health. The severity of obesity 24 and gut dysbiosis may partly explain the discrepancy with previous findings in less obese populations. A. muciniphila supplementation could be of interest in overweight/obese subjects, whereas it might be ineffective in severe obesity.