IntroductionThe timing of maternal exposure to air pollution is crucial to define metabolic changes in the offspring. Here we aimed to determine the most critical period of maternal exposure to particulate matter (PM2.5) that impairs offspring's energy metabolism and gut microbiota composition.MethodsUnexposed female and male C57BL/6J mice were mated. PM2.5 or filtered air (FA) exposure occurred only in gestation (PM2.5/FA) or lactation (FA/PM2.5). We studied the offspring of both genders.ResultsPM2.5 exposure during gestation increased body weight (BW) at birth and from weaning to young in male adulthood. Leptin levels, food intake, Agrp, and Npy levels in the hypothalamus were also increased in young male offspring. Ikbke, Tnf increased in male PM2.5/FA. Males from FA/PM2.5 group were protected from these phenotypes showing higher O2 consumption and Ucp1 in the brown adipose tissue. In female offspring, we did not see changes in BW at weaning. However, adult females from PM2.5/FA displayed higher BW and leptin levels, despite increased energy expenditure and thermogenesis. This group showed a slight increase in food intake. In female offspring from FA/PM2.5, BW, and leptin levels were elevated. This group displayed higher energy expenditure and a mild increase in food intake. To determine if maternal exposure to PM2.5 could affect the offspring’s gut microbiota, we analyzed alpha diversity by Shannon and Simpson indexes and beta diversity by the Linear Discriminant Analysis (LDA) in offspring at 30 weeks. Unlike males, exposure during gestation led to higher adiposity and leptin maintenance in female offspring at this age. Gestation exposure was associated with decreased alpha diversity in the gut microbiota in both genders.DiscussionOur data support that exposure to air pollution during gestation is more harmful to metabolism than exposure during lactation. Male offspring had an unfavorable metabolic phenotype at a young age. However, at an older age, only females kept more adiposity. Ultimately, our data highlight the importance of controlling air pollution, especially during gestation.
Fine particulate matter (PM2.5) is the most harmful component of air pollution and is associated with an increased risk of cardiometabolic diseases, such as T2DM. The small diameter of PM2.5 allows it to be inhaled and subsequently invades tissues through the airways. Intake of PM2.5 is also possible even if this is not the primary route of entry of PM2.5 into the body. However, it is still unclear whether ingestion and inhalation of PM2.5 in a short time would be sufficient to alter the gut microbiota and energy metabolism. Thus, we aimed to investigate whether 1 day or 5 days of exposure to PM2.5 would be enough to alter energy metabolism and the composition of gut microbiota at the phylum level. Male C57BL/6J mice on a chow diet were exposed to PM2.5 in a fixed dose (600 μg/m3/day) or filtered air (FA) for 1 day or 5 days using the Harvard Ambient Fine Particle Concentrator. The 1-day exposure to PM2.5 did not change body weight, food intake or energy expenditure, but altered the composition of the gut microbiota compared to the FA group. In the gut, there was a reduction of Bacteroidetes and Verrucomicrobia and an increase of Tenericutes. After 5 days of exposure to PM2.5, there was an increase in food intake, fat mass. In the gut, there was an increase in Firmicutes and in the ratio of Firmicutes/Bacteroidetes after 5 days of exposure to PM2.5 compared to the FA group. Thus, after a short period of exposure to air pollution, there was a significant change in the gut microbiota, beginning with the reduction of the Bacteroidetes and Verrucomicrobia phyla and the increase of the phylum Tenericutes with 1 day of exposure. This result occurred without altering the energy balance. A robust dysbiosis installation happened after 5 days of exposure to PM2.5, Firmicutes/Bacteroidetes ratio was elevated and associated with fat mass gain, and hyperphagia.
Disclosure
O.P. Zordão: None. A. Santos: None. C.M. Campolim: None. R. Ataíde Lima: None. C.K. Ferreira: None. M. Saad: None. P. Saldiva: None. M. Veras: None. P.O. Prada: None.
Funding
Sao Paulo Research Foundation (2017/18498-62017/19703-22017/11518-1)
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