Avelar-Barragan, J. | bioRxiv Science

bioRxiv2022

Longitudinal analysis of the gut microbiome in the 5xfAD mouse model of Alzheimer's disease

INTRODUCTIONMicrobial exposures impact Alzheimers disease (AD), and a baseline understanding of AD model microbiomes is vital for improving model efficacy. We describe the evaluation of the microbiome and metabolome in longitudinal samples from the 5xfAD transgenic mouse model. METHODSCecal and fecal samples from 5xfAD and wild-type B6J (WT) animals from 4- 18 months of age were subjected to DNA extraction and shotgun Illumina sequencing. Metabolomics was performed on plasma and feces from a subset of animals. RESULTSSignificant sex, age, and cage-specific differences were observed in the microbiome. Eight bacteria species were elevated in older 5xfAD mice and nine were depleted, including Turicibacter spp. Contradicting published findings covering persons with AD, plasma measurements revealed elevated serotonin in 18 month 5xfAD animals. DISCUSSIONTaken together, these findings strengthen the link between Turicibacter abundance and AD and provide a basis for further microbiome studies of murine models for AD.

microbiology↗

bioRxiv2021

Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps

BackgroundColorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is less clear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways. ResultsWe discovered significant differences between the microbiomes of colon mucosa and fecal samples, with sample type explaining 14% of the variation observed in the microbiome. Multiple mucosal samples were collected from each individual to investigate whether the gut microbiome differed between polyp and healthy intestinal tissue, but no differences were found. Colon mucosa sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 2-10% of the variance in the microbiome. Further analysis revealed differential abundances of 6 microbes and 1,143 microbial genes across tubular adenoma, serrated polyp, and polyp-free cases. ConclusionBy directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, this study helps characterize potential mechanistic targets for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each methods practicality and effect on microbial community composition.

microbiology↗