Major microbiota dysbiosis in severe obesity: fate after bariatric surgery

ObjectivesDecreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with...

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Veröffentlicht in:Gut 2019-01, Vol.68 (1), p.70-82
Hauptverfasser: Aron-Wisnewsky, Judith, Prifti, Edi, Belda, Eugeni, Ichou, Farid, Kayser, Brandon D, Dao, Maria Carlota, Verger, Eric O, Hedjazi, Lyamine, Bouillot, Jean-Luc, Chevallier, Jean-Marc, Pons, Nicolas, Le Chatelier, Emmanuelle, Levenez, Florence, Ehrlich, Stanislav Dusko, Dore, Joel, Zucker, Jean-Daniel, Clément, Karine
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container_end_page 82
container_issue 1
container_start_page 70
container_title Gut
container_volume 68
creator Aron-Wisnewsky, Judith
Prifti, Edi
Belda, Eugeni
Ichou, Farid
Kayser, Brandon D
Dao, Maria Carlota
Verger, Eric O
Hedjazi, Lyamine
Bouillot, Jean-Luc
Chevallier, Jean-Marc
Pons, Nicolas
Le Chatelier, Emmanuelle
Levenez, Florence
Ehrlich, Stanislav Dusko
Dore, Joel
Zucker, Jean-Daniel
Clément, Karine
description ObjectivesDecreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration number NCT01454232.
doi_str_mv 10.1136/gutjnl-2018-316103
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Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration number NCT01454232.</description><identifier>ISSN: 0017-5749</identifier><identifier>EISSN: 1468-3288</identifier><identifier>DOI: 10.1136/gutjnl-2018-316103</identifier><identifier>PMID: 29899081</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Adult ; Bariatric Surgery ; Biomarkers - blood ; Body composition ; Body fat ; Body mass index ; Body weight ; Chromatography, Liquid ; Comorbidity ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diet ; Dysbacteriosis ; Dysbiosis - etiology ; Female ; Gastric bypass ; Gastrointestinal Microbiome ; Gastrointestinal surgery ; Histidine ; Humans ; Inflammatory bowel disease ; Insulin resistance ; Intestinal microflora ; Life Sciences ; Liquid chromatography ; Male ; Mass Spectrometry ; Mass spectroscopy ; Metabolism ; Metabolites ; Metagenomics ; Microbiomes ; Microbiota ; Nutrition research ; Obesity ; Obesity, Morbid - microbiology ; Obesity, Morbid - surgery ; Overweight ; Phenotype ; Phenotypes ; Prospective Studies ; Protein families ; Protein turnover ; Risk Factors ; Surgery ; Weight control</subject><ispartof>Gut, 2019-01, Vol.68 (1), p.70-82</ispartof><rights>Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.</rights><rights>2019 Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b568t-d7d654bac24a0ed428ae9048b1576d273cccc17573f2539e280b6462df73383e3</citedby><cites>FETCH-LOGICAL-b568t-d7d654bac24a0ed428ae9048b1576d273cccc17573f2539e280b6462df73383e3</cites><orcidid>0000-0001-6284-7352 ; 0000-0001-8861-1305 ; 0000-0002-7563-4046 ; 0000-0002-5597-7922 ; 0000-0002-2489-3355 ; 0000-0002-8756-0718 ; 0000-0002-8689-8290 ; 0000-0001-6293-5133 ; 0000-0003-4619-6785 ; 0000-0002-2724-0536</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143256/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143256/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29899081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.inrae.fr/hal-02629250$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Aron-Wisnewsky, Judith</creatorcontrib><creatorcontrib>Prifti, Edi</creatorcontrib><creatorcontrib>Belda, Eugeni</creatorcontrib><creatorcontrib>Ichou, Farid</creatorcontrib><creatorcontrib>Kayser, Brandon D</creatorcontrib><creatorcontrib>Dao, Maria Carlota</creatorcontrib><creatorcontrib>Verger, Eric O</creatorcontrib><creatorcontrib>Hedjazi, Lyamine</creatorcontrib><creatorcontrib>Bouillot, Jean-Luc</creatorcontrib><creatorcontrib>Chevallier, Jean-Marc</creatorcontrib><creatorcontrib>Pons, Nicolas</creatorcontrib><creatorcontrib>Le Chatelier, Emmanuelle</creatorcontrib><creatorcontrib>Levenez, Florence</creatorcontrib><creatorcontrib>Ehrlich, Stanislav Dusko</creatorcontrib><creatorcontrib>Dore, Joel</creatorcontrib><creatorcontrib>Zucker, Jean-Daniel</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><title>Major microbiota dysbiosis in severe obesity: fate after bariatric surgery</title><title>Gut</title><addtitle>Gut</addtitle><description>ObjectivesDecreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration number NCT01454232.</description><subject>Adult</subject><subject>Bariatric Surgery</subject><subject>Biomarkers - blood</subject><subject>Body composition</subject><subject>Body fat</subject><subject>Body mass index</subject><subject>Body weight</subject><subject>Chromatography, Liquid</subject><subject>Comorbidity</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diet</subject><subject>Dysbacteriosis</subject><subject>Dysbiosis - etiology</subject><subject>Female</subject><subject>Gastric bypass</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal surgery</subject><subject>Histidine</subject><subject>Humans</subject><subject>Inflammatory bowel disease</subject><subject>Insulin resistance</subject><subject>Intestinal microflora</subject><subject>Life Sciences</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metagenomics</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Nutrition research</subject><subject>Obesity</subject><subject>Obesity, Morbid - microbiology</subject><subject>Obesity, Morbid - surgery</subject><subject>Overweight</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Prospective Studies</subject><subject>Protein families</subject><subject>Protein turnover</subject><subject>Risk Factors</subject><subject>Surgery</subject><subject>Weight control</subject><issn>0017-5749</issn><issn>1468-3288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUtv1DAUhS0EokPhD7BAltjAItSP-BEWlaoKKGgqNrC27ORm6iiJi-2MNP8ej1Iq2lW9sa_9nWP7HoTeUvKJUi7Pdkse5rFihOqKU0kJf4Y2tJalYlo_RxtCqKqEqpsT9CqlgRCidUNfohPW6KYhmm7Qj2s7hIgn38bgfMgWd4dUFskn7GecYA8RcHCQfD58xr3NgG2fIWJno7c5-hanJe4gHl6jF70dE7y5m0_R769ffl1eVduf375fXmwrJ6TOVac6KWpnW1ZbAl3NtIWG1NpRoWTHFG_LoEoo3jPBG2CaOFlL1vWKc82Bn6Lz1fd2cRN0Lcw52tHcRj_ZeDDBevPwZPY3Zhf2RtGaMyGLwcfV4OaR7Opia457hEnWMEH2tLAf7i6L4c8CKZvJpxbG0c4QlmQYEUJSpQUr6PtH6BCWOJdWGEYFF5pp3hSKrVRpeEoR-vsXUGKOsZo1VnOM1ayxFtG7_798L_mXYwGqFXDT8BTDvxDerW4</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Aron-Wisnewsky, Judith</creator><creator>Prifti, Edi</creator><creator>Belda, Eugeni</creator><creator>Ichou, Farid</creator><creator>Kayser, Brandon D</creator><creator>Dao, Maria Carlota</creator><creator>Verger, Eric O</creator><creator>Hedjazi, Lyamine</creator><creator>Bouillot, Jean-Luc</creator><creator>Chevallier, Jean-Marc</creator><creator>Pons, Nicolas</creator><creator>Le Chatelier, Emmanuelle</creator><creator>Levenez, Florence</creator><creator>Ehrlich, Stanislav Dusko</creator><creator>Dore, Joel</creator><creator>Zucker, Jean-Daniel</creator><creator>Clément, Karine</creator><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6284-7352</orcidid><orcidid>https://orcid.org/0000-0001-8861-1305</orcidid><orcidid>https://orcid.org/0000-0002-7563-4046</orcidid><orcidid>https://orcid.org/0000-0002-5597-7922</orcidid><orcidid>https://orcid.org/0000-0002-2489-3355</orcidid><orcidid>https://orcid.org/0000-0002-8756-0718</orcidid><orcidid>https://orcid.org/0000-0002-8689-8290</orcidid><orcidid>https://orcid.org/0000-0001-6293-5133</orcidid><orcidid>https://orcid.org/0000-0003-4619-6785</orcidid><orcidid>https://orcid.org/0000-0002-2724-0536</orcidid></search><sort><creationdate>20190101</creationdate><title>Major microbiota dysbiosis in severe obesity: fate after bariatric surgery</title><author>Aron-Wisnewsky, Judith ; Prifti, Edi ; Belda, Eugeni ; Ichou, Farid ; Kayser, Brandon D ; Dao, Maria Carlota ; Verger, Eric O ; Hedjazi, Lyamine ; Bouillot, Jean-Luc ; Chevallier, Jean-Marc ; Pons, Nicolas ; Le Chatelier, Emmanuelle ; Levenez, Florence ; Ehrlich, Stanislav Dusko ; Dore, Joel ; Zucker, Jean-Daniel ; Clément, Karine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b568t-d7d654bac24a0ed428ae9048b1576d273cccc17573f2539e280b6462df73383e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Bariatric Surgery</topic><topic>Biomarkers - blood</topic><topic>Body composition</topic><topic>Body fat</topic><topic>Body mass index</topic><topic>Body weight</topic><topic>Chromatography, Liquid</topic><topic>Comorbidity</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diet</topic><topic>Dysbacteriosis</topic><topic>Dysbiosis - etiology</topic><topic>Female</topic><topic>Gastric bypass</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal surgery</topic><topic>Histidine</topic><topic>Humans</topic><topic>Inflammatory bowel disease</topic><topic>Insulin resistance</topic><topic>Intestinal microflora</topic><topic>Life Sciences</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metagenomics</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Nutrition research</topic><topic>Obesity</topic><topic>Obesity, Morbid - microbiology</topic><topic>Obesity, Morbid - surgery</topic><topic>Overweight</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Prospective Studies</topic><topic>Protein families</topic><topic>Protein turnover</topic><topic>Risk Factors</topic><topic>Surgery</topic><topic>Weight control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aron-Wisnewsky, Judith</creatorcontrib><creatorcontrib>Prifti, Edi</creatorcontrib><creatorcontrib>Belda, Eugeni</creatorcontrib><creatorcontrib>Ichou, Farid</creatorcontrib><creatorcontrib>Kayser, Brandon D</creatorcontrib><creatorcontrib>Dao, Maria Carlota</creatorcontrib><creatorcontrib>Verger, Eric O</creatorcontrib><creatorcontrib>Hedjazi, Lyamine</creatorcontrib><creatorcontrib>Bouillot, Jean-Luc</creatorcontrib><creatorcontrib>Chevallier, Jean-Marc</creatorcontrib><creatorcontrib>Pons, Nicolas</creatorcontrib><creatorcontrib>Le Chatelier, Emmanuelle</creatorcontrib><creatorcontrib>Levenez, Florence</creatorcontrib><creatorcontrib>Ehrlich, Stanislav Dusko</creatorcontrib><creatorcontrib>Dore, Joel</creatorcontrib><creatorcontrib>Zucker, Jean-Daniel</creatorcontrib><creatorcontrib>Clément, Karine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes.DesignSixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included.ResultsLow gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients.ConclusionsWe identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome–host interactions in severe obesity.Trial registration number NCT01454232.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>29899081</pmid><doi>10.1136/gutjnl-2018-316103</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-6284-7352</orcidid><orcidid>https://orcid.org/0000-0001-8861-1305</orcidid><orcidid>https://orcid.org/0000-0002-7563-4046</orcidid><orcidid>https://orcid.org/0000-0002-5597-7922</orcidid><orcidid>https://orcid.org/0000-0002-2489-3355</orcidid><orcidid>https://orcid.org/0000-0002-8756-0718</orcidid><orcidid>https://orcid.org/0000-0002-8689-8290</orcidid><orcidid>https://orcid.org/0000-0001-6293-5133</orcidid><orcidid>https://orcid.org/0000-0003-4619-6785</orcidid><orcidid>https://orcid.org/0000-0002-2724-0536</orcidid><oa>free_for_read</oa></addata></record>
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1468-3288
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source MEDLINE; PubMed Central
subjects Adult
Bariatric Surgery
Biomarkers - blood
Body composition
Body fat
Body mass index
Body weight
Chromatography, Liquid
Comorbidity
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diet
Dysbacteriosis
Dysbiosis - etiology
Female
Gastric bypass
Gastrointestinal Microbiome
Gastrointestinal surgery
Histidine
Humans
Inflammatory bowel disease
Insulin resistance
Intestinal microflora
Life Sciences
Liquid chromatography
Male
Mass Spectrometry
Mass spectroscopy
Metabolism
Metabolites
Metagenomics
Microbiomes
Microbiota
Nutrition research
Obesity
Obesity, Morbid - microbiology
Obesity, Morbid - surgery
Overweight
Phenotype
Phenotypes
Prospective Studies
Protein families
Protein turnover
Risk Factors
Surgery
Weight control
title Major microbiota dysbiosis in severe obesity: fate after bariatric surgery
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