The gut microbiota, a complicated and highly dynamic ecosystem, consists of microorganisms that live within the gastrointestinal tract of its hosts and its structure and stability is relevant to the host health. The gut-brain axis of vertebrates is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the knowledge regarding the interactions between the gut microbiota and the nervous system (e.g., brain) is lacking. For example, the influence of chronic muscle pain with or without peripheral nerve injury on gut microbiota has not been extensively addressed. Here we used spared-nerve injury (SNI) model that mimics neuropathic pain and acid-induced muscle pain (AIMP) model that mimics fibromyalgia to investigate the link between chronic muscle pain and the dynamics of gut microbiota in C57BL/6 mice. We cut the peripheral nerves for SNI model and performed repeated muscle insult on the left gastrocnemius muscle using acidic saline for AIMP model, evaluated with pain behavioral test, and collected multiple fecal samples to generate time-series data. High-throughput amplicon sequencing coupled with mothur identified certain bacteria genera such as Adlercreutzia, Bifidobacterium, Muribacullum, Oscillospira, Staphylococcus, and Erysipelatoclostridium significantly affected by the chronic pain treatments. Microbial interaction network analysis based on generalized Lotka–Volterra (gLV) equations with multiple simulations showed the instability of gut microbial community when the mice were exhibiting chronic pain. Moreover, the metagenome imputation shed light on the functional profiles of gut microbial communities. Altogether, our bioinformatic analyses of mice gut microbiota indicated the impact of chronic pain on the structure and stability of gut microbial community in vertebrates.

Ai, D., Pan, H., Li, X., Wu, M., & Xia, L.C. (2019). Association network analysis identifies enzymatic components of gut microbiota that significantly differ between colorectal cancer patients and healthy controls. PeerJ, 7, 7315.

Agler, M.T., Ruhe, J., Kroll, S., Morhenn, C., Kim, S.T., Weigel, D., & Kemen, E.M. (2016). Microbial hub taxa link host and abiotic factors to plant microbiome variation. PLoS biology, 14, e1002352.

Alberts, B., Johnson, A., Lewis, J., Roberts, K., & Raff, M. (2002). Helper T cells and lymphocyte activation. Molecular Biology of the Cell. 4th edition. New York: Garland Science.

Ayres, J.S. (2016). Cooperative microbial tolerance behaviors in host-microbiota mutualism. Cell, 165, 1323-1331.

Ayres, J.S. (2013). Inflammasome-microbiota interplay in host physiologies. Cell host & microbe, 14, 491-497.

Ayala, D.I., Cook, P.W., Franco, J.G., Bugarel, M., Kottapalli, K.R., Loneragan, G.H., et al. (2019). A systematic approach to identify and characterize the effectiveness and safety of novel probiotic strains to control foodborne pathogens. Frontiers in microbiology, 10, 1108.

Bäckhed, F., Ding, H., Wang, T., Hooper, L.V., Koh, G.Y., Nagy, A., Semenkovich, C.F., & Gordon, J.I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America, 101, 15718-15723.

Bäckhed, F., Fraser, C.M., Ringel, Y., Sanders, M.E., Sartor, R.B., Sherman, P.M., et al. (2012). Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell host & microbe, 12, 611-622.

Baganz, N.L., & Blakely, R.D. (2013). A dialogue between the immune system and brain, spoken in the language of serotonin. ACS chemical neuroscience, 4, 48-63.

Banerjee, S., Schlaeppi, K., & van der Heijden, M. (2018). Keystone taxa as drivers of microbiome structure and functioning. Nature reviews. Microbiology, 16, 567-576.

Baron, R., Tolle, T.R., Gockel, U., Brosz, M., & Freynhagen, R. (2009). A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: Differences in demographic data and sensory symptoms. Pain, 146, 34-40.

Bazzocchi, G., Turroni, S., Bulzamini, M. C., D'Amico, F., Bava, A., Castiglioni, M., et al. (2021). Changes in gut microbiota in the acute phase after spinal cord injury correlate with severity of the lesion. Scientific reports, 11, 12743.

Berry, D., & Widder, S. (2014). Deciphering microbial interactions and detecting keystone species with co-occurrence networks. Frontiers in microbiology, 5, 219.

Bhattarai, Y., Williams, B.B., Battaglioli, E.J., et al. (2018). Gut microbiota-produced tryptamine activates an epithelial G-protein-coupled receptor to increase colonic secretion. Cell host & microbe, 23, 775-785.e5.

Biggs, M.B., Medlock, G.L., Moutinho, T.J., Lees, H.J., Swann, J.R., Kolling, G.L., & Papin, J.A. (2017). Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota. The ISME journal, 11, 426-438.

Blake, K.J, Baral, P., Voisin, T., Lubkin, A., Pinho-Ribeiro, F.A., Adams, K.L., et al. (2018). Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314. Nature communications, 9, 37.

Bliven, K.A., & Maurelli, A.T. (2016). Evolution of Bacterial Pathogens Within the Human Host. Microbiology spectrum, 4, 10.1128/microbiolspec.VMBF-0017-2015.

Boccella, S., Guida, F., Palazzo, E., Marabese, I., de Novellis, V., Maione, S., & Luongo, L. (2018). Spared nerve injury as a long-lasting model of neuropathic pain. Methods in molecular biology (Clifton, N.J.), 1727, 373-378.

Bordenstein, S.R., & Theis, K.R. (2015). Host biology in light of the microbiome: Ten principles of holobionts and hologenomes. PLoS biology, 13, e1002226.

Boon T. (1972). Inactivation of ribosomes in vitro by colicin E 3 and its mechanism of action. Proceedings of the National Academy of Sciences of the United States of America, 69, 549-552.

Bradley, L.A. (2009). Pathophysiology of fibromyalgia. Am J Med, 122, S22-30.

Brandon-Mong, G.J., Shaw, G.T.W., Chen, W.H., Chen, C.C., & Wang D. (2020). A network approach to investigating the key microbes and stability of gut microbial communities in a mouse neuropathic pain model. BMC microbiology, 20, 295.

Bravo, J.A., Forsythe, P., Chew, M.V., Escaravage, E., Savignac, H.M., Dinan, T.G., et al. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America, 108, 16050-1655.

Brüssow, H. (2019). Problems with the concept of gut microbiota dysbiosis. Microbial biotechnology, 13, 423-434.

Buchon, N., Silverman, N., & Cherry, S. (2014). Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology. Nature reviews. Immunology, 14, 796-810.

Cani, P.D., Amar, J., Iglesias, M.A., Poggi, M., Knauf, C., Bastelica, D. et al. (2007a). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56, 1761-1772.

Cani, P.D., Neyrinck, A.M., Fava, F., Knauf, C., Burcelin, R.G., Tuohy, K.M. et al. (2007b). Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia, 50, 2374-2383.

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28, 203-209.

Cascales, E., Buchanan, S.K., Duché, D., Kleanthous, C., Lloubès, R., Postle, K., Riley, M., Slatin, S., & Cavard, D. (2007). Colicin biology. Microbiology and molecular biology reviews : MMBR, 71, 158-229.

Castelli, V., Palumbo, P., d'Angelo, M., Moorthy, N.K., Antonosante, A., Catanesi, M., et al. (2018). Probiotic DSF counteracts chemotherapy induced neuropathic pain. Oncotarget, 9, 27998-28008.

Catanzaro, J.R., Strauss, J.D., Bielecka, A., Porto, A.F., Lobo, F.M., & Urban, A. (2019). IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM. Scientific reports, 9, 13574.

Chang, Y.T., Chen, W.H., Shih, H.C., Min, M.Y., Shyu, B.C., & Chen, C.C. (2019). Anterior nucleus of paraventricular thalamus mediates chronic mechanical hyperalgesia. Pain, 160, 1208-1223.

Charitou, T., Bryan, K., & Lynn, D.J. (2016). Using biological networks to integrate, visualize and analyze genomics data. Genetics, selection, evolution : GSE, 48, 27.

Chen, C.H. (2014). Staphylococcus saprophyticus bacteremia with pyelonephritis cured by gentamicin. Journal of the Formosan Medical Association = Taiwan yi zhi, 113, 483-484.

Chen, Q.L., Ding, J., Zhu, D., Hu, H.W., Delgado-Baquerizo, M., Ma, Y.B., et al. (2020). Rare microbial taxa as the major drivers of ecosystem multifunctionality in long-term fertilized soils. Soil Biology and Biochemistry, 141, 107686.

Chen, W.H., Chang, Y.T., Chen, Y.C., Cheng, S.J., & Chen, C.C. (2018). Spinal PKC/ERK signal pathway mediates hyperalgesia priming. Pain, 159, 907-918.

Cheng, H.Y., Ning, M.X., Chen, D.K., & Ma, W.T. (2019). Interactions between the gut microbiota and the host innate immune response against pathogens. Frontiers in immunology, 10, 607.

Clapp, M., Aurora, N., Herrera, L., Bhatia, M., Wilen, E., & Wakefield, S. (2017). Gut microbiota's effect on mental health: The gut-brain axis. Clinics and practice, 7, 987.

Clos-Garcia, M., Andrés-Marin, N., Fernández-Eulate, G., Abecia, L., Lavín, J.L., van Liempd, S., et al. (2019). Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia. EBioMedicine, 46, 499-511.

Colloca, L., Ludman, T., Bouhassira, D., Baron, R., Dickenson, A.H., Yarnitsky, D., et al. (2017). Neuropathic pain. Nature reviews. Disease primers, 3, 17002.

Coraggio, V., Guida, F., Boccella, S., Scafuro, M., Paino, S., Romano, D., et al. (2018). Neuroimmune-driven neuropathic pain establishment: A focus on gender differences. International journal of molecular sciences, 19, pii:E281.

Costa, N.R., Mendes, N., Marcos, N.T., Reis, C.A., Caffrey, T., Hollingsworth, M. A., & Santos-Silva, F. (2008). Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells. World journal of gastroenterology, 14, 1411-1414.

Costello, E.K., Stagaman, K., Dethlefsen, L., Bohannan, B.J., & Relman, D.A. (2012). The application of ecological theory toward an understanding of the human microbiome. Science, 336, 1255-1262.

Cotillard, A., Kennedy, S.P., Kong, L.C., Prifti, E., Pons, N., Le Chatelier, E., et al. (2013). Dietary intervention impact on gut microbial gene richness. Nature, 500, 585-588.

Coyte, K.Z., Schluter, J., Foster, K.R. (2015). The ecology of the microbiome: Networks, competition, and stability. Science, 350, 663-666.

Crook, R.J., Dickson, K., Hanlon, R.T., & Walters, E.T. (2014). Nociceptive sensitization reduces predation risk. Current biology : CB, 24, 1121-1125.

Crofford, L.J., Rowbotham, M.C., Mease, P.J., Russell, I.J., Dworkin, R.H., Corbin, A.E., et al. (2005). Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis and rheumatism, 52, 1264-1273.

Dean, S.N., Leary, D.H., Sullivan, C.J., Oh, E., & Walper, S.A. (2019). Isolation and characterization of Lactobacillus-derived membrane vesicles. Scientific reports, 9, 877.

Decosterd, I., & Woolf, C.J. (2000). Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain, 87, 149-158.

Douglas, S.M., Chubiz, L.M., Harcombe, W.R., & Marx, C.J. (2017). Identification of the potentiating mutations and synergistic epistasis that enabled the evolution of inter-species cooperation. PLoS ONE, 12, e0174345.

Douglas, S.M., Chubiz, L.M., Harcombe, W.R., Ytreberg, F.M., & Marx, C.J. (2016). Parallel mutations result in a wide range of cooperation and community consequences in a two-species bacterial consortium. PLoS ONE, 11, e0161837.

D'Souza, G., Shitut, S., Preussger, D., Yousif, G., Waschina, S., & Kost, C. (2018). Ecology and evolution of metabolic cross-feeding interactions in bacteria. Natural product reports, 35, 455-488.

Dickenson, A.H., & Ghandehari, J. (2007). Anti-convulsants and anti-depressants. Handbook of Experimental Pharmacology, 177, 145-177.

Duché, D., Parker, M.W., González-Mañas, J.M., Pattus, F., & Baty, D. (1994). Uncoupled steps of the colicin A pore formation demonstrated by disulfide bond engineering. The Journal of biological chemistry, 269, 6332-6339.

Edgar, R.C. (2013). UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nature methods, 10, 996-998.

El Ghachi, M., Bouhss, A., Barreteau, H., Touzé, T., Auger, G., Blanot, D., & Mengin-Lecreulx, D. (2006). Colicin M exerts its bacteriolytic effect via enzymatic degradation of undecaprenyl phosphate-linked peptidoglycan precursors. The Journal of biological chemistry, 281, 22761-22772.

Erdrich, S., Hawrelak, J.A., Myers, S.P., & Harnett, J.E. (2020). Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review. BMC musculoskeletal disorders, 21, 181.

Escobar, J.S., Klotz, B., Valdes, B.E., & Agudelo, G.M. (2014). The gut microbiota of Colombians differs from that of Americans, Europeans and Asians. BMC microbiology, 14, 311.

Euzéby, J.P. (1997). List of bacterial names with standing in nomenclature: a folder available on the Internet. International journal of systematic bacteriology, 47, 590-592.

Falony, G., Vieira-Silva, S., & Raes, J. (2018). Richness and ecosystem development across faecal snapshots of the gut microbiota. Nature microbiology, 3, 526-528.

Faust, K., & Raes, J. (2012). Microbial interactions: from networks to models. Nature reviews. Microbiology, 10, 538-550.

Fettweis, J.M., Serrano, M.G., Brooks, J.P., Edwards, D.J., Girerd, P.H., Parikh, H.I., et al. (2019). The vaginal microbiome and preterm birth. Nature medicine, 25, 1012-1021.

Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., et al. (2018). Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites. Cell reports, 22, 3072-3086.

Foster, T. Staphylococcus. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 12. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8448/

Fung, T.C., Olson, C.A., & Hsiao, E.Y. (2017). Interactions between the microbiota, immune and nervous systems in health and disease. Nature neuroscience, 20, 145-155.

Gebert, B., Fischer, W., Weiss, E., Hoffmann, R., & Haas, R. (2003). Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science, 301, 1099-1102.

Gentile, C.L., & Weir, T.L. (2018). The gut microbiota at the intersection of diet and human health. Science, 362, 776-780.

Ghoul, M., & Mitri, S. (2016). The ecology and evolution of microbial competition. Trends in microbiology, 24, 833-845.

González, A., Gálvez, N., Martín, J., Reyes, F., Pérez-Victoria, I., & Dominguez-Vera, J. M. (2017). Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. Food chemistry, 228, 374-380.

Gonze, D., Coyte, K.Z., Lahti, L., & Faust, K. (2018). Microbial communities as dynamical systems. Current opinion in microbiology, 44, 41-49.

Goodrich, J.K., Waters, J.L., Poole, A.C., Sutter, J.L., Koren, O., Blekhman, R., et al. (2014). Human genetics shape the gut microbiome. Cell, 159,789-799.

Gophna, U., Konikoff, T., Nielsen, & H.B. (2017). Oscillospira and related bacteria - From metagenomic species to metabolic features. Environmental microbiology, 19, 835-841.

Gou, Z., Jiang, S., Zheng, C., Tian, Z., & Lin, X. (2015). Equol inhibits LPS-induced oxidative stress and enhances the immune response in chicken HD11 macrophages. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 36, 611-621.

Guida, F., Boccella, S., Belardo, C., Iannotta, M., Piscitelli, F., De Filippis, F., et al. (2020). Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain. Brain, behavior, and immunity, 85, 128-141.

Guo, L., Xiao, P., Zhang, X., Yang, Y., Yang, M., Wang, T., et al. (2021). Inulin ameliorates schizophrenia via modulation of the gut microbiota and anti-inflammation in mice. Food & function, 12, 1156-1175.

Guo, R., Chen, L. H., Xing, C., & Liu, T. (2019). Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. British journal of anaesthesia, 123, 637-654.

Hadadi, N., Berweiler, V., Wang, H., & Trajkovski, M. (2021). Intestinal microbiota as a route for micronutrient bioavailability. Current opinion in endocrine and metabolic research, 20, 100285.

Halfvarson, J., Brislawn, C.J., Lamendella, R., Vázquez-Baeza, Y., Walters, W.A., Bramer, L.M., et al. (2017). Dynamics of the human gut microbiome in inflammatory bowel disease. Nature microbiology, 2, 17004.

Harcombe, W. (2010). Novel cooperation experimentally evolved between species. Evolution; international journal of organic evolution, 64, 2166-2172.

Harkness, R. E., & Braun, V. (1989). Colicin M inhibits peptidoglycan biosynthesis by interfering with lipid carrier recycling. The Journal of biological chemistry, 264, 6177-6182.

Heinken, A., & Thiele, I. (2015). Anoxic conditions promote species-specific mutualism between gut microbes in silico. Applied and environmental microbiology, 81, 4049-4061.

Herren, C. M., & McMahon, K. D. (2018). Keystone taxa predict compositional change in microbial communities. Environmental microbiology, 20, 2207-2217.

Hildebrand, F., Nguyen, T.L., Brinkman, B., Yunta, R.G., Cauwe, B., Vandenabeele, P., Liston, A., & Raes, J. (2013). Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice. Genome biology, 14, R4.

Hirano, H., & Takemoto, K. (2019). Difficulty in inferring microbial community structure based on co-occurrence network approaches. BMC bioinformatics, 20, 329.

Huang, J., Zhang, C., Wang, J., Guo, Q., & Zou, W. (2019). Oral Lactobacillus reuteri LR06 or Bifidobacterium BL5b supplement do not produce analgesic effects on neuropathic and inflammatory pain in rats. Brain and behavior, 9, e01260.

Hufeldt, M.R., Nielsen, D.S., Vogensen, F.K., Midtvedt, T., & Hansen, A.K. (2010). Variation in the gut microbiota of laboratory mice is related to both genetic and environmental factors. Comparative medicine, 60, 336-347.

Hugenholtz, F., & de Vos, W.M. (2018). Mouse models for human intestinal microbiota research: a critical evaluation. Cellular and molecular life sciences : CMLS, 75, 149-160.

Hur, J., Lee, A., Hong, J., Jo, W.Y., Cho, O.H., Kim, S., & Bae, I.G. (2016). Staphylococcus saprophyticus bacteremia originating from urinary tract infections: A Case Report and Literature Review. Infection & chemotherapy, 48, 136-139.

Indelli, P.F., Dillingham, M., Fanton, G., & Schurman, D.J. (2002). Septic arthritis in postoperative anterior cruciate ligament reconstruction. Clinical orthopaedics and related research, 398, 182-188.

Ishigaki, S., & Lockley M.G. (2010). Didactyl, tridactyl and tetradactyl theropod trackways from the Lower Jurassic of Morocco: evidence of limping, labouring and other irregular gaits. Historical biology, 22, 100-108.

Jang, J.H., Song, E.M., Do, Y.H., et al. (2021). Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex. Pain, 162, 514-530.

Jiang, D., Armour, C. R., Hu, C., Mei, M., Tian, C., Sharpton, T. J., & Jiang, Y. (2019). Microbiome multi-omics network analysis: Statistical considerations, limitations, and opportunities. Frontiers in genetics, 10, 995.

Johnson, K.V., & Burnet, P.W. (2016). Microbiome: Should we diversify from diversity? Gut Microbes, 7, 455-458.

Kaur, H., Bose, C., & Mande, S. S. (2019). Tryptophan metabolism by gut microbiome and gut-brain-axis: An in silico analysis. Frontiers in neuroscience, 13, 1365.

Khan, A.A., Yurkovetskiy, L., O'Grady, K., Pickard, J.M., de Pooter, R., Antonopoulos, D.A., Golovkina, T., & Chervonsky, A. (2019). Polymorphic immune mechanisms regulate commensal repertoire. Cell reports, 29, 541–550.e4.

Kim, Y.M., & Joo, Y.B. (2012). Clinical presentation of Staphylococcus epidermidis septic arthritis following anterior cruciate ligament reconstruction. Knee surgery & related research, 24, 46-51.

Kloppers, P.H., & Greeff, J.C. (2013). Lotka–Volterra model parameter estimation using experiential data. Applied mathematics and computation, 224, 817-825.

Koroschetz, J., Rehm, S.E., Gockel, U., Brosz, M., Freynhagen, R., Tölle, T.R., & Baron, R. (2011). Fibromyalgia and neuropathic pain--differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia. BMC neurology, 11, 55.

Kropp, C., Le Corf, K., Relizani, K., Tambosco, K., Martinez, C., Chain, F., Rawadi, G., Langella, P., Claus, S. P., & Martin, R. (2021). The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo. Scientific reports, 11, 11494.

Krych, L., Hansen, C.H., Hansen, A.K., van den Berg, F.W., & Nielsen, D.S. (2013). Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome. PLoS ONE, 8, e62578.

Kuhar, M. J., Couceyro, P. R., & Lambert, P. D. (1999). Biosynthesis of Catecholamines. Basic Neurochem. Mol. Cell. Med. Asp, 6th Edn. Available at: https://www.ncbi.nlm.nih.gov/books/NBK27988/ [accessed December 12, 2021].

Lagkouvardos, I., Lesker, T.R., Hitch, T.C.A., Gálvez, E.J.C., Smit, N., Neuhaus, K., et al. (2019). Sequence and cultivation study of Muribaculaceae reveals novel species, host preference, and functional potential of this yet undescribed family. Microbiome, 7, 28.

Lattanzio, S.M. (2017). Fibromyalgia syndrome: A metabolic approach grounded in biochemistry for the remission of symptoms. Frontiers in medicine, 4, 198.

Layeghifard, M., Hwang, D.M., & Guttman, D.S. (2017). Disentangling Interactions in the Microbiome: A Network Perspective. Trends in microbiology, 25, 217-228.

Leblois, J., Massart, S., Li, B., Wavreille, J., Bindelle, J., & Everaert N. (2017). Modulation of piglets' microbiota: differential effects by a high wheat bran maternal diet during gestation and lactation. Scientific reports, 7, 7426.

Levy, M., Thaiss, C.A., & Elinav, E. (2015). Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome. Genome medicine, 7, 120.

Lin, B., Wang, Y., Zhang, P., Yuan, Y., Zhang, Y., & Chen, G. (2020). Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. The journal of headache and pain, 21, 103.

Liu, X., Teng, T., Li, X., Fan, L., Xiang, Y., Jiang, Y., Du, K., Zhang, Y., Zhou, X., & Xie, P. (2021). Impact of inosine on chronic unpredictable mild stress-induced depressive and anxiety-like behaviors with the alteration of gut microbiota. Frontiers in cellular and infection microbiology, 11, 697640.

Liu, Y., Wu, X., & Jiang, H. (2019). High dietary fat intake lowers serum equol concentration and promotes prostate carcinogenesis in a transgenic mouse prostate model. Nutrition & metabolism, 16, 24.

Liu, Z., Wei, H., Zhang, J., Saleem, M., He, Y., Zhong, J., & Ma, R. (2021). Higher sensitivity of microbial network than community structure under acid rain. Microorganisms, 9, 118.

Lloyd-Price, J., Abu-Ali, G., & Huttenhower, C. (2016). The healthy human microbiome. Genome medicine, 8, 51.

Love, M.I., Huber, W., & Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome biology, 15, 550.

Lowy, F.D. (1998). Staphylococcus aureus infections. The New England journal of medicine, 339, 520-532.

Lozupone, C.A., Stombaugh, J., Gordon, J., Jansson, J.K., Knight, R. (2012). Diversity, stability and resilience of the human gut microbiota. Nature, 489, 220-230.

Luczynski, P., Tramullas, M., Viola, M., Shanahan, F., Clarke, G., O'Mahony, S., et al. (2017). Microbiota regulates visceral pain in the mouse. eLife, 6, e25887.

Ma, Q., Li, Y., Wang, J., Li, P., Duan, Y., Dai, H., et al. (2020). Investigation of gut microbiome changes in type 1 diabetic mellitus rats based on high-throughput sequencing. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 124, 109873.

Ma, B., Wang, H., Dsouza, M., Lou, J., He, Y., Dai, Z., Brookes, P.C., Xu, J., & Gilbert, J.A. (2016). Geographic patterns of co-occurrence network topological features for soil microbiota at continental scale in eastern China. The ISME journal, 10, 1891-1901.

Magnúsdóttir, S., Ravcheev, D., de Crécy-Lagard, V., & Thiele, I. (2015). Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Frontiers in genetics, 6, 148.

Mancabelli, L., Milani, C., Lugli, G.A., Turroni, F., Cocconi, D., van Sinderen, D., et al. (2017). Identification of universal gut microbial biomarkers of common human intestinal diseases by meta-analysis. FEMS microbiology ecology, 93, fix153.

Manichanh, C., Borruel, N., Casellas, F., & Guarner, F. (2012). The gut microbiota in IBD. Nature reviews. Gastroenterology & hepatology, 9, 599-608.

Martin, L.J., Tuttle, A.H., & Mogil, J.S. (2014). The interaction between pain and social behavior in humans and rodents. Current topics in behavioral neurosciences, 20, 233-250.

Martinson, V.G., Douglas, A.E., & Jaenike, J. (2017). Community structure of the gut microbiota in sympatric species of wild Drosophila. Ecology letters, 20, 629-639.

Maruo, T., Sakamoto, M., Ito, C., Toda, T., & Benno, Y. (2008). Adlercreutzia equolifaciens gen. nov., sp. nov., an equol-producing bacterium isolated from human faeces, and emended description of the genus Eggerthella. International journal of systematic and evolutionary microbiology, 58, 1221-1227.

Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Sawaki, E., Koga, Y., & Benno, Y. (2013). Cerebral low-molecular metabolites influenced by intestinal microbiota: a pilot study. Frontiers in systems neuroscience, 7, 9.

McGuckin, M.A., Lindén, S.K., Sutton, P., & Florin, T.H. (2011). Mucin dynamics and enteric pathogens. Nature reviews. Microbiology, 9, 265-278.

Medlock, G.L., Carey, M.A., McDuffie, D.G., Mundy, M.B., Giallourou, N., Swann, J.R., et al. (2018). Inferring metabolic mechanisms of interaction within a defined gut microbiota. Cell systems, 7, 245-257.

Mikaelyan, A., Thompson, C.L., Hofer, M.J., & Brune, A. (2015). Deterministic assembly of complex bacterial communities in guts of germ-free cockroaches. Applied and environmental microbiology, 82, 1256–1263.

Min, M. Y., Yang, H. W., Yen, C. T., Chen, C. C., Chen, C. C., & Cheng, S. J. (2011). ERK, synaptic plasticity and acid-induced muscle pain. Communicative & integrative biology, 4, 394-396.

Minerbi, A., Gonzalez, E., Brereton, N.J.B., Anjarkouchian, A., Dewar, K., Fitzcharles, M.A., Chevalier, S., & Shir, Y. (2019). Altered microbiome composition in individuals with fibromyalgia. Pain, 160, 2589-2602.

Mitri, S., & Foster, K.R. (2013). The genotypic view of social interactions in microbial communities. Annual review of genetics, 47, 247-273.

Miyake, S., Ding, Y., Soh, M., Low, A., & Seedorf, H. (2020). Muribaculum gordoncarteri sp. nov., an anaerobic bacterium from the faeces of C57BL/6J mice. International journal of systematic and evolutionary microbiology, 70, 4725-4729.

Montgomery, T. L., Künstner, A., Kennedy, J. J., Fang, Q., Asarian, L., Culp-Hill, R., D'Alessandro, A., Teuscher, C., Busch, H., & Krementsov, D. N. (2020). Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Proceedings of the National Academy of Sciences of the United States of America, 117, 27516–27527.

Nagel, R., Traub, R.J., Allcock, R.J., Kwan, M.M., & Bielefeldt-Ohmann, H. (2016). Comparison of faecal microbiota in Blastocystis-positive and Blastocystis-negative irritable bowel syndrome patients. Microbiome, 4, 47.

Nakamura, Y., Oscherwitz, J., Cease, K.B., Chan, S.M., Muñoz-Planillo, R., Hasegawa, M., et al. (2013). Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature, 503, 397-401.

Näpflin, K., & Schmid‐Hempel, P. (2018). Host effects on microbiota community assembly. Journal of animal ecology, 87, 331-340.

Näpflin, K., & Schmid-Hempel, P. (2016). Immune response and gut microbial community structure in bumblebees after microbiota transplants. Proceedings. Biological sciences, 283, 20160312.

Oksanen, J., Blanchet, F.G., Friendly, M., Kindt, R., Legendre, P., McGlinn, D., et al. (2019). vegan: Community Ecology Package. R package version 2.5-6. https://CRAN.R-project.org/package=vegan

Oliveira, L.R., de Melo, V.U., Macedo, F.N., Barreto, A.S., Badaue-Passos, D., Jr, Viana dos Santos, et al. (2012). Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats. Autonomic neuroscience : basic & clinical, 167, 45-49.

Pande, S., Merker, H., Bohl, K., Reichelt, M., Schuster, S., de Figueiredo, L. F., Kaleta, C., & Kost, C. (2014). Fitness and stability of obligate cross-feeding interactions that emerge upon gene loss in bacteria. The ISME journal, 8, 953-962.

Piewngam, P., Zheng, Y., Nguyen, T.H., Dickey, S.W., Joo, H.S., Villaruz, A.E., et al. (2018). Pathogen elimination by probiotic Bacillus via signalling interference. Nature, 562:532-537.

Qiu, Y., Zhang, T.J., Meng, L.B., Cheng, X.T., & Hua, Z. (2021). Bioinformatics analysis of gene and microRNA targets for fibromyalgia. Clinical and experimental rheumatology, 39, 21-31.

Rajilić-Stojanović, M., Biagi, E., Heilig, H.G., Kajander, K., Kekkonen, R.A., Tims, S., & de Vos, W.M. (2011). Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology, 141, 1792-1801.

Rooijakkers, S.H., Ruyken, M., Roos, A., Daha, M.R., Presanis, J.S., Sim, R.B., van Wamel, W.J., van Kessel, K.P., & van Strijp, J.A. (2005). Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nature immunology, 6, 920-927.

Rooks, M.G., & Garrett, W.S. (2016). Gut microbiota, metabolites and host immunity. Nature reviews. Immunology, 16, 341-352.

Scholz, B.A., Hammonds, C.L., & Boomershine, C.S. (2009). Duloxetine for the management of fibromyalgia syndrome. Journal of pain research, 2, 99-108.

Schloss, P.D., Westcott, S.L., Ryabin, T., Hall, J.R., Hartmann, M., Hollister, E.B., et al. (2009). Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Applied and environmental microbiology, 75, 7537-7541.

Schulfer, A.F., Battaglia, T., Alvarez, Y., Bijnens, L., Ruiz, V.E., Ho, M., et al. (2018). Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nature microbiology, 3, 234-242.

Schwarz, M.J., Offenbaecher, M., Neumeister, A., Ewert, T., Willeit, M., Praschak-Rieder, N., Zach, J., Zacherl, M., Lossau, K., Weisser, R., Stucki, G., & Ackenheil, M. (2002). Evidence for an altered tryptophan metabolism in fibromyalgia. Neurobiology of disease, 11, 434-442.

Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLoS biology, 14, e1002533.

Shade, A. (2017). Diversity is the question, not the answer. The ISME journal, 11, 1-6.

Shade, A., Jones, S.E., Caporaso, J.G., Handelsman, J., Knight, R., Fierer, N., & Gilbert, J.A. (2014). Conditionally rare taxa disproportionately contribute to temporal changes in microbial diversity. mBio, 5, e01371-14.

Shaw, G.T., Pao, Y.Y., & Wang, D. (2016). MetaMIS: a metagenomic microbial interaction simulator based on microbial community profiles. BMC bioinformatics, 17, 488.

Sheahan, T.D., Siuda, E.R., Bruchas, M.R., et al. (2017). Inflammation and nerve injury minimally affect mouse voluntary behaviors proposed as indicators of pain. Neurobiology of pain (Cambridge, Mass.), 2, 1-12.

Shields, S.D., Eckert, W.A.3rd., & Basbaum, A.I. (2003). Spared nerve injury model of neuropathic pain in the mouse: a behavioral and anatomic analysis. The journal of pain, 4, 465-470.

Sikander, A., Rana, S.V., & Prasad, K.K. (2009). Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clinica chimica acta; international journal of clinical chemistry, 403, 47–55.

Sluka, K.A., Kalra, A., & Moore, S.A. (2001). Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle & nerve, 24, 37-46.

Sommer, F., & Bäckhed, F. (2013). The gut microbiota--masters of host development and physiology. Nature reviews. Microbiology, 11, 227-238.

Smith, N.W., Shorten, P.R., Altermann, E., Roy, N.C., & McNabb, W.C. (2019). The Classification and Evolution of Bacterial Cross-Feeding. Frontiers in Ecology and Evolution, 7, 153.

Stein, R.R., Bucci, V., Toussaint, N.C., Buffie, C.G., Rätsch, G., & Pamer, E.G., et al. (2013). Ecological modeling from time-series inference: insight into dynamics and stability of intestinal microbiota. PLoS computational biology, 9, e1003388.

Szentirmai, É., Millican, N.S., Massie, A.R., & Kapás, L. (2019). Butyrate, a metabolite of intestinal bacteria, enhances sleep. Scientific reports, 9, 7035.

Tamboli, C.P., Neut, C., Desreumaux, P., & Colombel, J.F. (2004). Dysbiosis in inflammatory bowel disease. Gut, 53, 1-4.

Tansley, S.N., Tuttle, A.H., Wu, N., Tohyama, S., Dossett, K., Gerstein, L., et al. (2019). Modulation of social behavior and dominance status by chronic pain in mice. Genes, brain, and behavior, 18, e12514.

Tims, S., Derom, C., Jonkers, D.M., Vlietinck, R., Saris, W.H., Kleerebezem, M., et al. (2013). Microbiota conservation and BMI signatures in adult monozygotic twins. The ISME journal, 7, 707-717.

Toju, H., Tanabe, A. S., & Sato, H. (2018). Network hubs in root-associated fungal metacommunities. Microbiome, 6, 116.

Ueda, H. (2019). Systems Pathology of Neuropathic Pain and Fibromyalgia. Biological & pharmaceutical bulletin, 42, 1773-1782.

van Berlo, C. L., de Jonge, H. R., van den Bogaard, A. E., van Eijk, H. M., Janssen, M. A., & Soeters, P. B. (1987). gamma-Aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora. Gastroenterology, 93, 472-479.

Vankemmelbeke, M., Healy, B., Moore, G.R., Kleanthous, C., Penfold, C.N., & James, R. (2005). Rapid detection of colicin E9-induced DNA damage using Escherichia coli cells carrying SOS promoter-lux fusions. Journal of bacteriology, 187, 4900-4907.

Venturelli, O.S., Carr, A.C., Fisher, G., Hsu, R.H., Lau, R., Bowen, B.P., et al. (2018). Deciphering microbial interactions in synthetic human gut microbiome communities. Molecular systems biology, 14, e8157.

Verdam, F.J., Fuentes, S., de Jonge, C., Zoetendal, E.G., Erbil, R., Greve, J.W., Buurman, W.A., de Vos, W.M., & Rensen, S.S. (2013). Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring), 21, E607-E615.

Vierck, C.J., Wong, F., King, C.D., Mauderli, A.P., Schmidt, S., & Riley, J.L.3rd. (2014). Characteristics of sensitization associated with chronic pain conditions. The Clinical journal of pain, 30, 119-128.

Walters, E.T., & Williams, A. (2019). Evolution of mechanisms and behaviour important for pain. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 374, 20190275.

Wang, X., Li, X., & Ling, J. (2017). Streptococcus gordonii LuxS/autoinducer-2 quorum-sensing system modulates the dual-species biofilm formation with Streptococcus mutans. Journal of basic microbiology, 57, 605-616.

Wang, X., Sun, G., Feng, T., Zhang, J., Huang, X., Wang, T., et al. (2019). Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell research, 29, 787-803.

Welsch, P., Uceyler, N., Klose, P., Walitt, B., & Hauser, W. (2018). Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. The Cochrane database of systematic reviews, 2, CD010292.

Weiss, S., Van Treuren, W., Lozupone, C., Faust, K., Friedman, J., Deng, Y., et al. (2016). Correlation detection strategies in microbial data sets vary widely in sensitivity and precision. The ISME journal, 10, 1669-1681.

Weiss, S., Xu, Z.Z., Peddada, S., Amir, A., Bittinger, K., Gonzalez, A., et al. (2017). Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome, 5, 27.

Weng, F.C., Shaw, G.T., Weng, C.Y., Yang, Y.J., & Wang, D. (2017). Inferring microbial interactions in the gut of the Hong Kong whipping frog (Polypedates megacephalus) and a validation using probiotics. Frontiers in microbiology, 8, 525.

XLSTAT. Statistical Software for Excel. 2007. https://www.xlstat.com

Yang, C., Fang, X., Zhan, G., Huang, N., Li, S., Bi. J., et al. (2019). Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain. Translational psychiatry. 9, 57.

Yang, J., Park, J., Park, S., Baek, I., & Chun, J. (2019). Introducing murine microbiome database (MMDB): A curated database with taxonomic profiling of the healthy mouse gastrointestinal microbiome. Microorganisms, 7, 480.

Yang, S., Boudier-Revéret, M., Choo, Y. J., & Chang, M. C. (2020). Association between chronic pain and alterations in the mesolimbic dopaminergic system. Brain sciences, 10, 701.

Yang, T.Y., Chen, C.S., Lin, C.L., Lin, W.M., Kuo, C.N., & Kao, C.H. (2017). Risk for irritable bowel syndrome in fibromyalgia patients: A national database study. Medicine (Baltimore). 96, e6657.

Yu, H., Kim, P. M., Sprecher, E., Trifonov, V., & Gerstein, M. (2007). The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS computational biology, 3, e59.

Zaneveld, J.R., McMinds, R., & Vega Thurber, R. (2017). Stress and stability: applying the Anna Karenina principle to animal microbiomes. Nature microbiology, 2, 17121.

Zamkovaya, T., Foster, J. S., de Crécy-Lagard, V., & Conesa, A. (2021). A network approach to elucidate and prioritize microbial dark matter in microbial communities. The ISME journal, 15, 228–244.