Abstract PR04: Potential of metformin to modify the gut microbiota and prevent inflammation in nondiabetic people with HIV
Notice bibliographique
Résumé
Abstract Background: Persisting inflammation is associated with increased risk of comorbidities and cancer development in people living with HIV (PLWH) under antiretroviral therapy (ART). Indeed, our observations show that a low CD4/CD8 ratio is predictive of the number of polyps in the colon in those people. Mechanistically, we and other have shown that coinfection with viruses such as cytomegalovirus and gut damage inducing microbial translocation induce inflammation in ART-treated PLWH. Metformin, an antidiabetic drug with antiaging effect, was shown to decrease inflammation by improving glucose metabolism and changing gut microbiota composition in diabetic people and in nondiabetic women with polycystic ovary syndrome. In healthy men, metformin was also associated with modification of the gut microbiota. In PLWH, the gut microbiota is different than the general population, and its composition was associated with inflammatory profiles. Herein, we report results from the LILAC (CIHR/CTN PT027) pilot clinical trial evaluating the effect of 12 weeks of metformin on blood/gut inflammation and gut microbial composition in nondiabetic PLWH on ART. Methods: A total of 22 nondiabetic (HbA1c <6%) PLWH, on ART with undetectable viral load for more than 3 years and CD4/CD8 ratio ≤0.7, received 12 weeks of metformin 850 mg bid. Blood and stools were collected at baseline (V1), after 12 weeks of metformin (V2), and 12 weeks after metformin discontinuation (V3). Soluble CD14 was measured in plasma. DNA was extracted from stools and 16S rRNA sequenced. Bacterial microbiota composition variations were analyzed using LefSe. Serum short chain fatty acids (SCFA) were measured by LC-MS. The beneficial Akkermansia muciniphila, enriched in stools of diabetic people initiating metformin, was quantified by qPCR. Results: CD4 T-cell count, CD4/CD8, and HbA1c levels did not vary between visits; however, plasma sCD14 levels decreased at V2 and V3 compared to V1. Bacterial alpha diversity tended to increase at V2 and V3. However, we observed a significant increase of Escherichia/Shigella and Lachnoclostridium and a decrease of Collinsella abundances at V2 compared to V1. A. muciniphila abundance was increased at V2. Abundance of Lachnospiraceae, specialized in butyrate production, was increased at V3 compared to V1. Accordingly, we found increased serum butyrate/isobutyrate levels at V2 and V3 compared to V1. No differences were observed for other SCFA propionate, succinate, and methylmalonate. Conclusion: A 12-week metformin therapy in nondiabetic PLWH on ART was safe and decreased plasma levels of the inflammatory marker sCD14 in association with an enrichment of butyrate-producing bacteria in stools and increased serum butyrate levels. As microbiota composition was associated with response to cancer therapy (especially immunotherapy), metformin use should be tested before immunotherapy. This abstract is also being presented as Poster A15. Citation Format: Stéphane Isnard, John Lin, Brandon Frombuena, Thibaut V. Varin, André Marette, Delphine Planas, Meriem Messaoudene, Bertrand Routy, Claude Van Der Ley, Ido Kema, Petronela Ancuta, Jonathan Angel, Jean-Pierre Routy. Potential of metformin to modify the gut microbiota and prevent inflammation in nondiabetic people with HIV [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR04.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».