Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery
ABSTRACT Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established precli...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.05109-22 |
| _version_ | 1797803435010031616 |
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| author | Mohammed K. Hankir Petia Kovatcheva-Datchary Rebecca Springer Annett Hoffmann Jörg Vogel Florian Seyfried Tulika Arora |
| author_facet | Mohammed K. Hankir Petia Kovatcheva-Datchary Rebecca Springer Annett Hoffmann Jörg Vogel Florian Seyfried Tulika Arora |
| author_sort | Mohammed K. Hankir |
| collection | DOAJ |
| description | ABSTRACT Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes. |
| first_indexed | 2024-03-13T05:20:48Z |
| format | Article |
| id | doaj.art-fd91c89e5a494084bf4b8d863853e154 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:20:48Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-fd91c89e5a494084bf4b8d863853e1542023-06-15T13:18:33ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.05109-22Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass SurgeryMohammed K. Hankir0Petia Kovatcheva-Datchary1Rebecca Springer2Annett Hoffmann3Jörg Vogel4Florian Seyfried5Tulika Arora6Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wurzburg, Wurzburg, GermanyInstitute for Molecular Infection Biology, University of Wurzburg, Wurzburg, GermanyDepartment of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wurzburg, Wurzburg, GermanyDepartment of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wurzburg, Wurzburg, GermanyInstitute for Molecular Infection Biology, University of Wurzburg, Wurzburg, GermanyDepartment of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Wurzburg, Wurzburg, GermanyNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkABSTRACT Roux-en-Y gastric bypass surgery (RYGB) leads to improved glycemic control in individuals with severe obesity beyond the effects of weight loss alone. Here, We addressed the potential contribution of gut microbiota in mediating this favourable surgical outcome by using an established preclinical model of RYGB. 16S rRNA sequencing revealed that RYGB-treated Zucker fatty rats had altered fecal composition of various bacteria at the phylum and species levels, including lower fecal abundance of an unidentified Erysipelotrichaceae species, compared with both sham-operated (Sham) and body weight-matched to RYGB-treated (BWM) rats. Correlation analysis further revealed that fecal abundance of this unidentified Erysipelotrichaceae species linked with multiple indices of glycemic control uniquely in RYGB-treated rats. Sequence alignment of this Erysipelotrichaceae species identified Longibaculum muris to be the most closely related species, and its fecal abundance positively correlated with oral glucose intolerance in RYGB-treated rats. In fecal microbiota transplant experiments, the improved oral glucose tolerance of RYGB-treated compared with BWM rats could partially be transferred to recipient germfree mice, independently of body weight. Unexpectedly, providing L. muris as a supplement to RYGB recipient mice further improved oral glucose tolerance, while administering L. muris alone to chow-fed or Western style diet-challenged conventionally raised mice had minimal metabolic impact. Taken together, our findings provide evidence that the gut microbiota contributes to weight loss-independent improvements in glycemic control after RYGB and demonstrate how correlation of a specific gut microbiota species with a host metabolic trait does not imply causation. IMPORTANCE Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota. While it is clear that RYGB is superior to dieting when it comes to improving glycemic control, the extent to which the gut microbiota contributes to this effect remains untested. In the present study, we uniquely linked fecal Erysipelotrichaceae species, including Longibaculum muris, with indices of glycemic control after RYGB in genetically obese and glucose-intolerant rats. We further show that the weight loss-independent improvements in glycemic control in RYGB-treated rats can be transmitted via their gut microbiota to germfree mice. Our findings provide rare causal evidence that the gut microbiota contributes to the health benefits of metabolic surgery and have implications for the development of gut microbiota-based treatments for type 2 diabetes.https://journals.asm.org/doi/10.1128/spectrum.05109-22gastric bypass surgeryglycemic controlgut microbiotacaloric restrictiongermfree mice |
| spellingShingle | Mohammed K. Hankir Petia Kovatcheva-Datchary Rebecca Springer Annett Hoffmann Jörg Vogel Florian Seyfried Tulika Arora Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery Microbiology Spectrum gastric bypass surgery glycemic control gut microbiota caloric restriction germfree mice |
| title | Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery |
| title_full | Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery |
| title_fullStr | Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery |
| title_full_unstemmed | Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery |
| title_short | Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery |
| title_sort | gut microbiota contribution to weight independent glycemic improvements after gastric bypass surgery |
| topic | gastric bypass surgery glycemic control gut microbiota caloric restriction germfree mice |
| url | https://journals.asm.org/doi/10.1128/spectrum.05109-22 |
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