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 | |
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 | |
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] |