@article{fdi:010084679, title = {{T}he human gut microbiota contributes to type-2 diabetes non-resolution 5-years after {R}oux-en-{Y} gastric bypass}, author = {{D}ebedat, {J}. and {L}e {R}oy, {T}. and {V}oland, {L}. and {B}elda, {E}. and {A}lili, {R}. and {A}driouch, {S}. and {L}assen, {P}. {B}. and {K}asahara, {K}. and {H}utchison, {E}. and {G}enser, {L}. and {T}orres, {L}. and {G}amblin, {C}. and {R}ouault, {C}. and {Z}ucker, {J}ean-{D}aniel and {K}apel, {N}. and {P}oitou, {C}. and {M}arcelin, {G}. and {R}ey, {F}. {E}. and {A}ron-{W}isnewsky, {J}. and {C}lement, {K}.}, editor = {}, language = {{ENG}}, abstract = {{R}oux-en-{Y} gastric bypass ({RYGB}) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes ({T}2{D}) improvements in patients with severe obesity and {T}2{D}. {W}e hypothesized a causal implication of the gut microbiota ({GM}) in these metabolic benefits, as {RYGB} is known to deeply impact its composition. {I}n a cohort of 100 patients with baseline {T}2{D} who underwent {RYGB} and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their {T}2{D} ({S}evere vs {M}ild) throughout the follow-up. {W}e identified via nanopore-based {GM} sequencing that the more severe cases of unresolved {T}2{D} were associated with a major increase of the class {B}acteroidia, including 12 species comprising {P}hocaeicola dorei, {B}acteroides fragilis, and {B}acteroides caecimuris. {A} key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in {B}acteroidia, as those who presented mild cases of {T}2{D} at all times. {I}n a separate group of 36 patients with similar baseline clinical characteristics and preoperative {GM} sequencing, we showed that this increase in {B}acteroidia was already present at baseline in the most severe cases of {T}2{D}. {T}o explore the causal relationship linking this enrichment in {B}acteroidia and metabolic alterations, we selected 13 patients across {T}2{D} severity clusters at 5-years and performed fecal matter transplants in mice. {O}ur results show that 14 weeks after the transplantations, mice colonized with the {GM} of {S}evere donors have impaired glucose tolerance and insulin sensitivity as compared to {M}ild-recipients, all in the absence of any difference in body weight and composition. {GM} sequencing of the recipient animals revealed that the hallmark {T}2{D}-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. {T}herefore, our results further establish the {GM} as a key contributor to long-term glucose metabolism improvements (or lack thereof) after {RYGB}.}, keywords = {{M}icrobiota ; bariatric surgery ; diabetes remission ; bacteroides ; fecal ; matter transplantation ; relapse ; type-2 diabetes ; clustering ; roux-en-{Y} ; gastric bypass ; obesity ; {FRANCE}}, booktitle = {}, journal = {{G}ut {M}icrobes}, volume = {14}, numero = {1}, pages = {2050635 [24 p.]}, ISSN = {1949-0976}, year = {2022}, DOI = {10.1080/19490976.2022.2050635}, URL = {https://www.documentation.ird.fr/hor/fdi:010084679}, }