| Summary: | This systematic review aims to provide a comprehensive understanding of the current literature regarding gut microbiota composition in patients with Parkinson’s disease (PD) and Alzheimer’s disease (AD) compared to healthy controls. To identify the relevant studies, a thorough search of PubMed, Medline, and Embase was conducted following the PRISMA guidelines. Out of 5627 articles, 73 studies were assessed for full-text eligibility, which led to the inclusion of 42 studies (26 PD and 16 AD studies). The risk of bias assessment showed a medium risk in 32 studies (20 PD studies and 12 AD studies), a low risk in 9 studies (5 PD studies and 4 AD studies), and 1 PD study with a high risk. Among the PD studies, 22 out of 26 studies reported a different gut microbiota composition between the PD cases and the healthy controls, and 15 out of 16 AD studies reported differences in gut microbiota composition between the AD cases and the healthy controls. The PD and AD studies consistently identified the phyla Bacteroidetes, Firmicutes, and Proteobacteria as prevalent in the gut microbiota in both the healthy groups and the case groups. Microbial dysbiosis was specifically characterized in the PD studies by a high abundance of <i>Akkermansia</i>, <i>Verrucomicrobiaceae</i>, <i>Lachnospiraceae</i>, and <i>Ruminococcaceae</i> in the cases and a high abundance of <i>Blautia</i>, <i>Coprococcus</i>, <i>Prevotellaceae</i>, and <i>Roseburia</i> in the controls. Similarly, Bacteroides and Acidobacteriota were abundant in the AD cases, and <i>Acidaminococcaceae</i>, Firmicutes, <i>Lachnospiraceae</i>, and <i>Ruminiclostridium</i> were abundant in the AD controls. The microbial signature assessment showed the association of several microbial taxa, including <i>Akkermansia</i>, <i>Lachnospiraceae</i>, <i>Verrucomicrobiaceae</i>, <i>Bifidobacterium</i>, <i>Ruminococcacea</i>, and Verrucomicrobia with PD and <i>Ruminococcaceae</i>, <i>Bacteroides</i>, and Actinobacteria with AD. The microbial diversity evaluations in the PD and AD studies indicated comparable alpha diversity in some groups and distinct gut microbiota composition in others, with consistent beta diversity differences between the cases and the controls across multiple studies. The bacterial signatures identified in this study that are associated with PD and AD may offer promising prospects for efficient management and treatment approaches.
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