The Role of the Human Microbiome in the Pathogenesis of Pain

Ustianowska, Klaudia; Ustianowski, Łukasz; Machaj, Filip; Gorący, Anna; Rosik, Jakub; Szostak, Bartosz; Szostak, Joanna; Pawlik, Andrzej

doi:10.3390/ijms232113267

Cited by 37 publications

(35 citation statements)

References 171 publications

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“…An accumulating body of evidence has highlighted the existence of bidirectional interplay between the microbiome and CNS, and this interaction [ 3 ], the so-called gut–brain axis, has an impact on mood change [ 3 , 4 , 5 ], sleep disorders [ 6 ] and cognitive impairment [ 7 ], which are commonly reported in patients with FMS. In addition, recent studies have revealed that the composition of the gut microbiome can play a role in the central sensitization of chronic pain by regulating astrocytes, microglia, and other immune cells [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia

Kim

Kang

2023

IJERPH

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Background: The present study aimed to evaluate microbial diversity, taxonomic profiles, and fecal short chain fatty acid (SCFA) in female patients with fibromyalgia syndrome (FMS). Methods: Forty participants (19 patients with FMS and 21 controls) were included in the study, and the diagnosis of FMS was made based on the revised American College of Rheumatology criteria. DNA extraction from fecal samples and 16S rRNA gene sequencing were conducted to estimate microbial composition. To compare alpha diversity, the Shannon index accounting for both evenness and richness, Pielou’s evenness, and Faith’s phylogenetic diversity (PD) were calculated. Unweighted and weighted UniFrac distances, Jaccard distance, and Bray–Curtis dissimilarity were used to calculate beta diversity. Furthermore, stool metabolites were analyzed using gas chromatography-mass spectrometry, and a generalized regression model was used to compare the SCFA of stools between FMS and healthy controls. Results: Compared with the control, patients with FMS had lower observed OTU (p = 0.048), Shannon’s index (p = 0.044), and evenness (p < 0.001). Although patients with FMS had a lower PD than did controls, statistical significance was not reached. We observed significant differences in unweighted (p = 0.007), weighted UniFrac-based diversity (p < 0.005), Jaccard distance (p < 0.001), and Bray–Curtis dissimilarity (p < 0.001) between the two groups. Although the FMS groups showed lower propionate levels compared with those of the control group, only marginal significance was observed (0.82 [0.051] mg/g in FMS vs. 1.16 [0.077] mg/g in the control group, p = 0.069). Conclusions: The diversity of the microbiome in the FMS group was lower than that in the control group, and the reduced stool propionate levels could be associated with the decreased abundance of propionate-producing bacteria.

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Section: Introductionmentioning

confidence: 99%

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia

Kim

Kang

2023

IJERPH

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“…Estrogen has been reported to stimulate neural growth and differentiation both in vitro ( 63 ) and in animal studies ( 64 ). The gut-brain axis promotes the central sensitization of chronic pain ( 65 ). Therefore, endometriosis-associated pain may be affected by regulation of microglia and astrocytes via the dysbiotic gut-brain axis ( 65 ).…”

Section: Resultsmentioning

confidence: 99%

“…The gut-brain axis promotes the central sensitization of chronic pain ( 65 ). Therefore, endometriosis-associated pain may be affected by regulation of microglia and astrocytes via the dysbiotic gut-brain axis ( 65 ). Severe pain and infertility associated with endometriosis have been reported to be associated with decreased cervical microbial diversity and abundance ( 66 ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, fecal microbiota transplantation is a promising therapeutic option to target Clostridium difficile infections and holds promise in developing novel therapeutics for multiple sclerosis, autism, obesity and other systemic diseases ( 74 ). Additionally, the gut microbiota could induce inflammatory pain in endometriosis by increasing glutamate and decreasing gamma-aminobutyric acid levels through modulation of microglia, astrocytes and immune cells ( 65 ). Fecal microbiota transplantation has been reported to be a potential treatment option for endometriosis due to its beneficial effects in reducing pain despite the absence of no clinical data ( 74 ).…”

Section: Resultsmentioning

confidence: 99%

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Gut and reproductive tract microbiota: Insights into the pathogenesis of endometriosis (Review)

Kobayashi

2023

Biomed Rep

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Endometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.

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“…Interestingly, T reg lymphocytes alleviate chronic neuropathic pain by inhibiting the Th1 response via CD4+ helper cells 42 . Emerging clinical evidence proposes that the pathogenesis of neuropathic pain may be a centrally-mediated neuroimmune phenomenon with an important contribution by the gut microbiome 43 , e.g. by influencing the balance between pro-inflammatory and anti-inflammatory T cells 44 .…”

Section: Discussionmentioning

confidence: 99%

Expanding the Characterization of Microbial Ecosystems using DIA-PASEF Metaproteomics

Gómez-Varela

Xian

Grundtner

et al. 2023

Preprint

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Metaproteomics is gaining momentum in microbiome research due to the multi-dimensional information it provides. However, current approaches have reached their detection limits. We present a highly-sensitive metaproteomic workflow using the extra information captured by Parallel Accumulation-Serial Fragmentation (PASEF) technology. The comparison of different acquisition modes and data analysis software packages showed that DIA-PASEF and DIA-NN doubled protein identifications of mouse gut microbiota and, importantly, also of the host proteome. DIA-PASEF significantly improved peptide detection reproducibility and quantification accuracy, which resulted in more than twofold identified taxa, reaching depths comparable to metagenomic studies. Consequently, DIA-PASEF exhibited improved coverage of functional networks revealing 131 additional pathways compared to DDA-PASEF. We applied our optimized workflow to a pre-clinical mouse model of chronic pain, in which we deciphered novel host-microbiome interactions. In summary, we present here a metaproteomic approach that paves the way for increasing the functional characterization of microbiome ecosystems and is applicable to diverse fields of biological research.

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The Role of the Human Microbiome in the Pathogenesis of Pain

Cited by 37 publications

References 171 publications

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia

Microbial Composition and Stool Short Chain Fatty Acid Levels in Fibromyalgia

Gut and reproductive tract microbiota: Insights into the pathogenesis of endometriosis (Review)

Expanding the Characterization of Microbial Ecosystems using DIA-PASEF Metaproteomics

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