Dutta Moumita, Weigel Kris M, Patten Kelley T, Valenzuela Anthony E, Wallis Christopher, Bein Keith J, Wexler Anthony S, Lein Pamela J, Cui Julia Yue
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Department of Molecular Biosciences, University of California Davis (UC Davis) School of Veterinary Medicine, Davis, CA, USA.
Toxicol Rep. 2022 Mar 10;9:432-444. doi: 10.1016/j.toxrep.2022.03.003. eCollection 2022.
Traffic-related air pollution (TRAP) is linked to increased risk for age-related dementia, including Alzheimer's disease (AD). The gut microbiome is posited to influence AD risk, and an increase in microbial-derived secondary bile acids (BAs) is observed in AD patients. We recently reported that chronic exposure to ambient TRAP modified AD risk in a sex-dependent manner in the TgF344 AD (TG) rat.
In this study, we used samples from the same cohort to test our hypothesis that TRAP sex-dependently produces gut dysbiosis and increases secondary BAs to a larger extent in the TG rat relative to wildtype (WT) controls.
Male and female TG and age-matched WT rats were exposed to either filtered air (FA) or TRAP from 28 days up to 15 months of age (n = 5-6). Tissue samples were collected after 9 or 14months of exposure.
At 10 months of age, TRAP tended to decrease the alpha diversity as well as the beneficial taxa and uniquely in male TG rats as determined by 16 S rDNA sequencing. A basal decrease in Firmicutes/Bacteroidetes ( ratio was also noted in TG rats at 10 months. At 15 months of age, TRAP altered inflammation-related bacteria in the gut of female rats from both genotypes. BAs were more affected by chronic TRAP exposure in females, with a general trend of increase in host-produced unconjugated primary and microbiota-produced secondary BAs. Most of the mRNAs of the hepatic BA-processing genes were not altered by TRAP, except for a down-regulation of the BA-uptake transporter Ntcp in males.
In conclusion, chronic TRAP exposure produced distinct gut dysbiosis and altered BA homeostasis in a sex and host genotype-specific manner.
交通相关空气污染（TRAP）与年龄相关性痴呆（包括阿尔茨海默病（AD））风险增加有关。肠道微生物群被认为会影响AD风险，并且在AD患者中观察到微生物衍生的次级胆汁酸（BAs）增加。我们最近报道，在TgF344 AD（TG）大鼠中，长期暴露于环境TRAP会以性别依赖的方式改变AD风险。
在本研究中，我们使用来自同一队列的样本，以检验我们的假设，即TRAP在TG大鼠中相对于野生型（WT）对照以性别依赖的方式导致肠道菌群失调，并更大程度地增加次级BAs。
雄性和雌性TG大鼠以及年龄匹配的WT大鼠从28天龄至15月龄暴露于过滤空气（FA）或TRAP（n = 5 - 6）。在暴露9或14个月后收集组织样本。
在10月龄时，通过16S rDNA测序确定，TRAP倾向于降低雄性TG大鼠的α多样性以及有益类群 和 。在10月龄的TG大鼠中还注意到厚壁菌门/拟杆菌门（ ）比率的基础下降。在15月龄时，TRAP改变了两种基因型雌性大鼠肠道中与炎症相关的细菌。雌性大鼠的BAs受长期TRAP暴露的影响更大，宿主产生的未结合初级胆汁酸和微生物群产生的次级胆汁酸总体呈增加趋势。除了雄性中胆汁酸摄取转运蛋白Ntcp的下调外，肝脏胆汁酸加工基因的大多数mRNA未被TRAP改变。
总之，长期TRAP暴露以性别和宿主基因型特异性方式导致明显的肠道菌群失调并改变胆汁酸稳态。
