Maternal heme-enriched diet promotes a gut pro-oxidative status associated with microbiota alteration, gut leakiness and glucose intolerance in mice offspring

被引：5

作者：

Mazenc, Anais ^{[1
]}

Mervant, Loic ^{[1
,2
]}

Maslo, Claire ^{[1
]}

Lencina, Corinne ^{[1
]}

Bezirard, Valerie ^{[1
]}

Leveque, Mathilde ^{[1
]}

Ahn, Ingrid ^{[1
]}

Alquier-Bacquie, Valerie ^{[1
]}

Naud, Nathalie ^{[1
]}

Helies-Toussaint, Cecile ^{[1
]}

Debrauwer, Laurent ^{[1
,2
]}

Chevolleau, Sylvie ^{[1
,2
]}

Gueraud, Francoise ^{[1
]}

Pierre, Fabrice H. F. ^{[1
]}

Theodorou, Vassilia ^{[1
]}

Olier, Maiwenn ^{[1
,3
]}

机构：

[1] Univ Toulouse, Toxalim Res Ctr Food Toxicol, INRAE, ENT,INP Purpan,UPS, Toulouse, France

[2] MetaboHUB, Metatoul AXIOM Plaform, Natl Infrastruct Metabol & Flux, Toulouse, France

[3] Toxalim, UMR INRAE 1331, 180 Chemin Tournefeuille,BP93173, F-31027 Toulouse, France

来源：

REDOX BIOLOGY | 2022年 / 53卷

关键词：

Heme iron; Early life nutrition; Lipoperoxidation; Red meat; Gut barrier; Gut microbiota; Glucose metabolism; COLON CARCINOGENESIS; DIABETES-MELLITUS; RED MEAT; INTESTINAL MICROBIOTA; LIPID-PEROXIDATION; IRON; STRESS; RISK; HYPERPROLIFERATION; CONSEQUENCES;

D O I：

10.1016/j.redox.2022.102333

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Maternal environment, including nutrition and microbiota, plays a critical role in determining offspring's risk of chronic diseases such as diabetes later in life. Heme iron requirement is amplified during pregnancy and lactation, while excessive dietary heme iron intake, compared to non-heme iron, has shown to trigger acute oxidative stress in the gut resulting from reactive aldehyde formation in conjunction with microbiota reshape. Given the immaturity of the antioxidant defense system in early life, we investigated the extent to which a maternal diet enriched with heme iron may have a lasting impact on gut homeostasis and glucose metabolism in 60-day-old C3H/HeN mice offspring. As hypothesized, the form of iron added to the maternal diet differentially governed the offspring's microbiota establishment despite identical fecal iron status in the offspring. Importantly, despite female offspring was unaffected, oxidative stress markers were however higher in the gut of male offspring from heme enriched-fed mothers, and were accompanied by increases in fecal lipocalin-2, intestinal para-cellular permeability and TNF-alpha expression. In addition, male mice displayed blood glucose intolerance resulting from impaired insulin secretion following oral glucose challenge. Using an integrated approach including an aldehydomic analysis, this male-specific phenotype was further characterized and revealed close covariations between unidentified putative reactive aldehydes and bacterial communities belonging to Bacteroidales and Lachnospirales orders. Our work highlights how the form of dietary iron in the maternal diet can dictate the oxidative status in gut offspring in a sex-dependent manner, and how a gut microbiota-driven oxidative challenge in early life can be associated with gut barrier defects and glucose metabolism disorders that may be predictive of diabetes development.

引用

页数：11