Microbiota-dependent and -independent effects of obesity on transplant rejection and hyperglycemia.
Am J Transplant
; 23(10): 1526-1535, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37356668
ABSTRACT
Obesity is associated with dysbiosis and a state of chronic inflammation that contributes to the pathogenesis of metabolic diseases, including diabetes. We have previously shown that obese mice develop glucose intolerance, increased alloreactivity, and accelerated transplant rejection. In the present study, we investigated the influence of the microbiota on diet-induced obesity (DIO)-associated transplant rejection and hyperglycemia. Antibiotic treatment prolonged graft survival and reduced fasting glycemia in high-fat diet (HFD)-fed specific-pathogen-free (SPF) mice, supporting a role for the microbiota in promoting accelerated graft rejection and hyperglycemia induced by DIO. Further supporting a microbiota-dependent effect, fecal microbiota transfer from DIO SPF mice into germ-free mice also accelerated graft rejection when compared with lean mice-fecal microbiota transfer. Notably, HFD could be also detrimental to the graft independently from microbiota, obesity, and hyperglycemia. Thus, whereas HFD-associated hyperglycemia was exclusively microbiota-dependent, HFD affected transplant outcomes via both microbiota-dependent and -independent mechanisms. Importantly, hyperglycemia in DIO SPF mice could be reduced by the addition of the gut commensal Alistipes onderdonkii, which alleviated both HFD-induced inflammation and glucose intolerance. Thus, microbial dysbiosis can be manipulated via antibiotics or select probiotics to counter some of the pathogenic effects of obesity in transplantation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Intolerância à Glucose
/
Microbioma Gastrointestinal
/
Hiperglicemia
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos