Guillain-Barré syndrome (GBS) is a potential major cause of an immune-mediated acute flaccid paralysis disorder characterized by inflammatory cell infiltration, demyelination, and axonal damage to the peripheral nervous system (PNS) (van den Berg et al., 2014). About two-thirds of GBS patients are triggered by previous infectious agents, such as Campylobacter jejuni, Cytomegalovirus, Zika virus, and Dengue virus (Liu et al., 2018). Humoral and cell-mediated autoimmune responses to recent infections are thought to be involved in the pathogenesis of GBS (Wakerley and Yuki, 2013). Activated T cells, macrophages, and cytokines participate in the inflammatory process of GBS (Shahrizaila et al., 2021).

Normal microorganisms in human beings include bacteria, fungi, viruses, archaea, and eukaryotic organisms, trillions of them live within the human gastrointestinal (GI) tract, and they make up what is collectively called the gut microbiome (Cryan et al., 2019). There are about 1014 bacterial cells in the human GI tract (Picca et al., 2018). The Human Gut Metagenomics and Human Microbiome Project provides the most complete view of human-related microbes, with 2172 species currently reported isolated from humans. They were divided into 12 distinct phyla, of which 93.5 % belong to Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetesphyla (Hugon et al., 2015). During the first days at the beginning of life, the gut microbiota (GM) is unstable and not very diverse, with age the GM gets relatively stable (Golofast and Vales, 2020). Many factors, such as genetics, sex, lifestyle, illness, smoking, drug addiction, place of residence, and climate, can affect GM (Blum, 2017). The microbiota participates in the process of homeostasis and greatly influences human health by producing various bioactive molecules (Golofast and Vales, 2020). GM is not only linked to GI function but also to several complex modulatory processes, for example, inflammation and immune response, glucose and bone metabolism, and peripheral and central neurotransmission (Zhao et al., 2019). GM plays a crucial role in innate and adaptive immunity (Olszak et al., 2012). The alteration of GM composition can induce lymphocyte aggregation and changes in the digestive tract barrier, thereby affecting the immune system function (Artis, 2008). The communication between microorganisms and intestinal mucosal cell regulate various cytokines and chemokines, including interleukin (IL)-8, IL-1, and IL-10 etc (Neish, 2009) Brooks PT et al. found that transplanted human fecal microbiota enhanced the autoantibody response of GBS, which indicated that the composition of colonic microbiota is another factor regulating susceptibility to GBS (Brooks et al., 2017). However, there haven't been studies that successfully explored GM and the risk of GBS.

With the increasing popularity of genome-wide association studies (GWAS) databases, Mendelian randomization (MR) research has received more attention. As opposed to randomized controlled trials (RCTs) results that can be influenced by confounding factors, MR utilizes instrumental variables (IVs) to research the genetic causality of exposure and outcome, which can mimic RCTs and is expected to be a reliable statistical method (Davies et al., 2018; Bennett and Holmes, 2017). Accumulating studies have verified the effects of GM on the risk of autoimmune diseases by MR studies (Xu et al., 2021; Xu et al., 2023). Therefore, in here, a two-sample MR (TSMR) study was carried out to explore the causal relationship between GM and GBS using the GWAS database, providing theoretical basis and new ideas for prevention and treatment of GBS.