Alterations in Gut Microbiota Co‐Occurrence Networks in the Alzheimer’s Disease Continnum

阿尔茨海默病连续谱中肠道菌群共现网络的改变

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Abstract

BACKGROUND: The gastrointestinal system hosts the intestinal microbiota—a diverse community of microorganisms, including bacteria, fungi, and viruses. Emerging evidence suggests that alterations in the intestinal microbiota may be linked to the development of Alzheimer's disease (AD). However, these evidences comes from studies in the Global North. This pilot study aims to explore whether gut bacterial communities are associated with the clinical stages of Alzheimer's disease (AD) in a small cohort in the south of Brazil. METHOD: This study was conducted with 12 elderly participants classified as cognitively unimpaired (CU), mild cognitive impairment (MCI), or Alzheimer's disease (AD). Fecal samples were sequenced using the Illumina MiSeq™ platform, targeting the V3–V4 regions of the 16S rRNA gene. The sequences were processed using the DADA2 pipeline, generating Amplicon Sequence Variants (ASVs) that were taxonomically classified with the SILVA database. To analyze microbial interactions, centered log‐ratio (CLR) transformed abundance data were used to construct correlation networks between genera across the cognitive groups. RESULT: A reduction in bacterial abundance and connectivity was observed across the stages of AD (Figure 1). Despite differences in abundance, certain bacterial groups were present at all stages, namely Lachnospiraceae, Bacteroidaceae, and Prevotella. Changes were observed in the genera Prevotella_7 and Bacteroides_pectinophilus_group, which were abundant in CU individuals, but showed a gradual decrease in abundance in MCI and AD patients. CAG_56 became reduced in MCI and absent in the AD group. Additionally, the interactions involving Roseburia and Megamonas were altered across the different stages of the disease. CONCLUSION: Our findings support the hypothesis that disruptions in the gut microbiota network are associated clinical stages of AD. The observed decline in microbial interactions and the persistence of certain bacterial groups across disease stages, suggests that those may play a role in the neurodegenerative process. Future studies involving a larger number of participants from this cohort are needed to explore potential interactions between microbiota‐gut‐brain and AD in this underrepresented population.

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