Gut microbiota genus network reflects Alzheimer’s disease clinical stages

Abstract

AbstractBackgroundBidirectional communication through the gut‐brain axis is fundamental to maintaining physiological functions. Imbalance in the intestinal microbial composition due to taxonomic or functional dysbiosis may be related to increased deposition of amyloid‐β plaques and tau tangles, which are the main hallmarks of Alzheimer’s disease (AD). We hypothesized that dysfunctional associations between the bacterial groups of the gut microbiota could be associated with AD clinical stages. Thus, we compared gut‐microbiota networks in cognitively unimpaired (CU), mild cognitive impaired (MCI), and AD dementia individuals.MethodsWe selected 16S rRNA gene sequencing data from fecal samples of CU, MCI and AD (n = 30, per group) available at NCBI repository (PRJNA489760). Individuals of both sexes aged between 57 and 73 years were included in the study. Adaptors were removed from the FASTQ files using the Trimmomatic tool for each sample and submitted to the DADA2 pipeline. Briefly, after filter and trimming, amplicon sequence variants (ASVs) were inferred using the dada function, taxonomic assignment was implemented using the SILVA resource and normalized by rarefaction without replacement. Afterward, normalized centered‐log ratio transformed abundance data were used to construct correlation networks between genus for CU, MCI, and AD.ResultsWe observed different correlation patterns between bacterial genera in CU, MCI, and AD. More especially, we found a progressive increase in network density toward AD clinical progression. Genus reportedly associated with cerebral amyloidosis and tau show few connections in the CU individuals (Figure 1A), which are increased in MCI (Figure 1B) and highly connected in AD (Figure 1C). Interestingly, we also noted that the opportunistic pathogen Escherichia_Shigella, strongly associated with AD pathology, was exclusively present in the AD network and showed a negative correlation with Faecalibacterium, a reportedly indicator of health.ConclusionMicrobial association networks at the genus level reflect different pathological stages of AD and could provide insights into preventive therapeutic strategies aiming to delay disease progression through the modulation of the gut microbiota.