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Table 1 Microbial mediators/species associated with the underlying mechanisms of neuropathic pain

From: Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy

Microbial mediators or species Function Potential mechanisms related to neuropathic pain References
LPS Activate TLR4 TLR4 contributes to neuropathic pain Kawai et al. (2010) [31]
Activate TRPA1 in a TLR4-independent and membrane-delimited manner The activation of TRPA1 can evoke nociceptive neurons depolarization and firing Meseguer et al. (2014) [32]
Activate TRPV1-mediated capsaicin responses via TLR4 Capsaicin responses lead to the excitation of nociception neurons Diogenes et al. (2011) [33]
Bacterial flagellin Activate TLR5 TLR5 facilitates the release of pro-inflammatory mediators Kawai et al. (2010) [31]
Activate TLR5 TLR5-mediated A-fiber blockade inhibits mechanical allodynia Kawai et al. (2010) [31]
Indole, LPS Regulate the secretion of GLP-1 GLP-1 is associated with pain hypersensitivity Chimerel et al. (2014) [34], Nguyen et al. (2014) [35]
SCFAs Activate microglia The activation of microglia leads to pain hypersensitivity Borre et al. (2014) [36]
Stimulates the production of PYY and GLP-1 in a FFAR2 and FFAR3 receptors dependent way GLP-1, PYY are associated with pain hypersensitivity Tolhurst et al. (2012) [37], Psichas et al. (2015) [38], Lin et al. (2012) [39]
PUFAs An endogenous agonist of TRPV4 The activation of TRPV4 leads to peripheral hypersensitivity Cenac et al.(2015) [40]
Bacteria-derived secondary bile acids Facilitates the release of GLP-1 and PYY via TRG5 GLP-1, PYY are associated with pain hypersensitivity Ullmer et al. (2013) [41], Thomas et al. (2009) [42], Katsuma et al. (2005) [43]
Lactobacillus fermentum KBL374 and KBL375 Increase IL-10 secretion while decrease pro-inflammatory mediators secretion IL-10 is associated with anti-inflammatory effects Jang et al. (2019) [28]
Bacteroides fragilis Facilitate the polarization of macrophages to M1 type and enhance their phagocytosis M1 macrophages can release pro-inflammatory cytokines and express TLRs Deng et al. (2016) [44]
Escherichia coli, Lactobacillus Synthesize GABA GABA can reverse allodynia in the neuropathic pain model Zhao et al. (2017) [45], Wu et al. (2017) [46]
Escherichia coli, Streptococcus spp., and Enterococcus spp. Produce 5-HT 5-HT serve as a special regulator in NP Guo et al. (2019) [11]
Corynebacterium glutamicum Produce glutamate Glutamate can affect hyperalgesia in neuropathic pain models Nakayama et al. (2018) [47], Yang et al. (2017) [48], Persicke et al. (2015) [49]
Lactobacillus, Peptostreptococcus, Clostridium sporogenes Generate AHR ligands derived from tryptophan Act directly on astrocytes through AHR and limit inflammation and neurodegeneration Zelante et al. (2013) [50], Wlodarska et al.(2017) [51], Dodd et al. (2017) [52]
DSF formulation Attenuate inflammatory signals Neutralize the influence of upregulation of TRPV1 and TRPV4 induced by paclitaxel Castelli et al. (2018) [53]
  1. Abbreviations: LPS lipopolysaccharide, TLR Toll-like receptor, TRPA1 transient receptor potential cation channel, subfamily A, member 1, TRPV1 transient receptor potential cation channel, subfamily V, member 1, TRPV4 transient receptor potential cation channel, subfamily V, member 4, SCFAs short-chain fatty acids, PUFAs polyunsaturated fatty acids, GABA γ-aminobutyric acid, GLP-1 glucagon-like peptide 1, PYY peptide YY, FFAR free fatty acid receptor, TRG5 G protein-coupled bile acid receptor, AHR aryl hydrocarbon receptor, IL-10 interleukin-10