Publication Cover
Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
Latest Articles
103
Views
0
CrossRef citations to date
0
Altmetric
Review Article

Treating chronic stress and chronic pain by manipulating gut microbiota with diet: can we kill two birds with one stone?

&

References

  • Abdallah CG, Geha P. Chronic pain and chronic stress: two sides of the same coin? Chronic Stress (Thousand Oaks). 2017;1:2470547017704763. doi:10.1177/2470547017704763.
  • Vachon-Presseau E. Effects of stress on the corticolimbic system: implications for chronic pain. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87(Pt B):216–23. doi:10.1016/j.pnpbp.2017.10.014
  • Fülöp B, Hunyady Á, Bencze N, Kormos V, Szentes N, Dénes Á, et al. IL-1 Mediates chronic stress-induced hyperalgesia accompanied by microglia and astroglia morphological changes in pain-related brain regions in mice. Int J Mol Sci. 2023;24(6):5479. doi:10.3390/ijms24065479
  • Sharp TJ, Harvey AG. Chronic pain and posttraumatic stress disorder: mutual maintenance? Clin Psychol Rev. 2001;21(6):857–77. doi:10.1016/S0272-7358(00)00071-4
  • Hart RP, Wade JB, Martelli MF. Cognitive impairment in patients with chronic pain: the significance of stress. Curr Pain Headache Rep. 2003;7:116–26. doi:10.1007/s11916-003-0021-5
  • Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017;82(7):472–87. doi:10.1016/j.biopsych.2016.12.031
  • Guo R, Chen L-H, Xing C, Liu T. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth. 2019a;123(5):637–54. doi:10.1016/j.bja.2019.07.026
  • Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926–38. doi:10.1172/JCI76304
  • Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterol Clin North Am. 2017;46(1):77–89. doi:10.1016/j.gtc.2016.09.007
  • Wu M, Tian T, Mao Q, Zou T, Zhou CJ, Xie J, Chen JJ. Associations between disordered gut microbiota and changes of neurotransmitters and short-chain fatty acids in depressed mice. Transl Psychiatry. 2020;10(1):350. doi:10.1038/s41398-020-01038-3
  • Li H, Xiang Y, Zhu Z, Wang W, Jiang Z, Zhao M, et al. Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat. J Neuroinflammation. 2021;18(1):254. doi:10.1186/s12974-021-02303-y
  • van de Wouw M, Boehme M, Lyte JM, Wiley N, Strain C, O'Sullivan O, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol. 2018;596(20):4923–44. doi:10.1113/JP276431
  • Santoni M, Miccini F, Battelli N. Gut microbiota, immunity and pain. Immunol Lett. 2021;229:44–7. doi:10.1016/j.imlet.2020.11.010
  • Cruz-Pereira JS, Moloney GM, Bastiaanssen TFS, Boscaini S, Tofani G, Borras-Bisa J, et al. Prebiotic supplementation modulates selective effects of stress on behavior and brain metabolome in aged mice. Neurobiol Stress. 2022;21:100501. doi:10.1016/j.ynstr.2022.100501
  • Chen P, Li X, Yu Y, Zhang J, Zhang Y, Li C, et al. Administration time and dietary patterns modified the effect of inulin on CUMS-induced anxiety and depression. Mol Nutr Food Res. 2023;67(8):e2200566. doi:10.1002/mnfr.202200566
  • McIntosh K, Reed DE, Schneider T, Dang F, Keshteli AH, De Palma G, et al. FODMAPs alter symptoms and the metabolome of patients with IBS: a randomised controlled trial. Gut. 2017;66(7):1241–51. doi:10.1136/gutjnl-2015-311339
  • De Palma G, Shimbori C, Reed DE, Yu Y, Rabbia V, Lu J, et al. Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice. Sci Transl Med. 2022;14(655):eabj1895. doi:10.1126/scitranslmed.abj1895
  • Sugiyama Y, Mori Y, Nara M, Kotani Y, Nagai E, Kawada H, et al. Gut bacterial aromatic amine production: aromatic amino acid decarboxylase and its effects on peripheral serotonin production. Gut Microbes. 2022;14(1):2128605. doi:10.1080/19490976.2022.2128605
  • Musumeci G, Castrogiovanni P, Castorina S, Imbesi R, Szychlinska MA, Scuderi S, et al. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet. Brain Res Bull. 2015;119(Pt A):12–8. doi:10.1016/j.brainresbull.2015.09.010
  • Han XM, Qin YJ, Zhu Y, Zhang XL, Wang NX, Rang Y, et al. Development of an underivatized LC-MS/MS method for quantitation of 14 neurotransmitters in rat hippocampus, plasma and urine: application to CUMS induced depression rats. J Pharm Biomed Anal. 2019;174:683–95. doi:10.1016/j.jpba.2019.06.043
  • Wang D, Wu J, Zhu P, Xie H, Lu L, Bai W, et al. Tryptophan-rich diet ameliorates chronic unpredictable mild stress induced depression- and anxiety-like behavior in mice: the potential involvement of gut-brain axis. Food Res Int. 2022a;157:111289. doi:10.1016/j.foodres.2022.111289
  • Di Paola M, Bonechi E, Provensi G, Costa A, Clarke G, Ballerini C, et al. Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in peyer's patches of mice. Sci Rep. 2018;8(1):14881. doi:10.1038/s41598-018-32925-x
  • Vijay A, Kouraki A, Gohir S, Turnbull J, Kelly A, Chapman V, et al. The anti-inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids. Gut Microbes. 2021;13(1):1997559. doi:10.1080/19490976.2021.1997559
  • Guida F, Boccella S, Belardo C, Iannotta M, Piscitelli F, De Filippis F, et al. Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain. Brain Behav Immun. 2020;85:128–41. doi:10.1016/j.bbi.2019.04.006
  • Costa A, Rani B, Bastiaanssen TFS, Bonfiglio F, Gunnigle E, Provensi G, et al. Diet prevents social stress-induced maladaptive neurobehavioural and gut microbiota changes in a histamine-dependent manner. Int J Mol Sci. 2022;23(2):862. https://doi.org/10.3390/ijms23020862.
  • Provensi G, Schmidt SD, Boehme M, Bastiaanssen TFS, Rani B, Costa A, et al. Preventing adolescent stress-induced cognitive and microbiome changes by diet. Proc Natl Acad Sci U S A. 2019;116(19):9644–51. doi:10.1073/pnas.1820832116
  • Costantini L, Molinari R, Farinon B, Merendino N. Impact of omega-3 fatty acids on the gut microbiota. Int J Mol Sci. 2017;18(12):2645. doi:10.3390/ijms18122645.
  • Weng RX, Wei YX, Li YC, Xu X, Zhuang JB, Xu GY, Li R. Folic acid attenuates chronic visceral pain by reducing clostridiales abundance and hydrogen sulfide production. Mol Pain. 2023;19:17448069221149834.
  • Allen JM, Jaggers RM, Solden LM, Loman BR, Davies RH, Mackos AR, et al. Dietary oligosaccharides attenuate stress-induced disruptions in immune reactivity and microbial B-vitamin metabolism. Front Immunol. 2019;10:1774. doi:10.3389/fimmu.2019.01774
  • Kirmiz N, Robinson RC, Shah IM, Barile D, Mills DA. Milk glycans and their interaction with the infant-gut microbiota. Annu Rev Food Sci Technol. 2018;9:429–50. doi:10.1146/annurev-food-030216-030207
  • Pichler MJ, Yamada C, Shuoker B, Alvarez-Silva C, Gotoh A, Leth ML, et al. Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways. Nat Commun. 2020;11(1):3285. doi:10.1038/s41467-020-17075-x
  • Šuligoj T, Vigsnæs LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, et al. Effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients. 2020;12(9):2808. doi:10.3390/nu12092808
  • Ferrier L, Eutamène H, Siegwald L, Marquard AM, Tondereau V, Chevalier J, et al. Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis. J Nutr Biochem. 2022;99:108865. doi:10.1016/j.jnutbio.2021.108865
  • Mesías M, Delgado-Andrade C. Melanoidins as a potential functional food ingredient. Current Opinion in Food Science. 2017;14:37–42. doi:10.1016/j.cofs.2017.01.007
  • Pérez-Burillo S, Rajakaruna S, Pastoriza S, Paliy O, Ángel Rufián-Henares J. Bioactivity of food melanoidins is mediated by gut microbiota. Food Chem. 2020;316:126309. doi:10.1016/j.foodchem.2020.126309
  • Rajakaruna S, Pérez-Burillo S, Kramer DL, Rufián-Henares J, Paliy O. Dietary melanoidins from biscuits and bread crust alter the structure and short-chain fatty acid production of human gut microbiota. Microorganisms. 2022;10(7):1268. doi:10.3390/microorganisms10071268.
  • Emami Kazemabad MJ, Asgari Toni S, Tizro N, Dadkhah PA, Amani H, Akhavan Rezayat S, et al. Pharmacotherapeutic potential of pomegranate in age-related neurological disorders. Front Aging Neurosci. 2022;14:955735. doi:10.3389/fnagi.2022.955735
  • Millman JF, Okamoto S, Teruya T, Uema T, Ikematsu S, Shimabukuro M, Masuzaki H. Extra-virgin olive oil and the gut-brain axis: influence on gut microbiota, mucosal immunity, and cardiometabolic and cognitive health. Nutr Rev. 2021;79(12):1362–74. doi:10.1093/nutrit/nuaa148
  • Farag MA, Hariri MLM, Ehab A, Homsi MN, Zhao C, von Bergen M. Cocoa seeds and chocolate products interaction with gut microbiota; mining microbial and functional biomarkers from mechanistic studies, clinical trials and 16S rRNA amplicon sequencing. Crit Rev Food Sci Nutr. 2024;64(10):3122–38.
  • Rocchetti G, Luisa Callegari M, Senizza A, Giuberti G, Ruzzolini J, Romani A, et al. Oleuropein from olive leaf extracts and extra-virgin olive oil provides distinctive phenolic profiles and modulation of microbiota in the large intestine. Food Chem. 2022;380:132187. doi:10.1016/j.foodchem.2022.132187
  • Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav Immun. 2011;25(3):397–407. doi:10.1016/j.bbi.2010.10.023
  • Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102(31):11070–5. doi:10.1073/pnas.0504978102
  • Tilg H, Moschen AR, Kaser A. Obesity and the microbiota. Gastroenterology. 2009;136(5):1476–83. doi:10.1053/j.gastro.2009.03.030
  • Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest. 2011;121(6):2126–32. doi:10.1172/JCI58109
  • Cândido FG, Valente FX, Grześkowiak Ł, Moreira APB, Rocha DMUP, Alfenas RCG. Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity. Int J Food Sci Nutr. 2018;69(2):125–43. doi:10.1080/09637486.2017.1343286
  • Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302(9):G966–978. doi:10.1152/ajpgi.00380.2011
  • Qamar N, Castano D, Patt C, Chu T, Cottrell J, Chang SL. Meta-analysis of alcohol induced gut dysbiosis and the resulting behavioral impact. Behav Brain Res. 2019;376:112196. doi:10.1016/j.bbr.2019.112196
  • Shukla R, Ghoshal U, Dhole TN, Ghoshal UC. Fecal microbiota in patients with irritable bowel syndrome compared with healthy controls using real-time polymerase chain reaction: an evidence of dysbiosis. Dig Dis Sci. 2015;60:2953–62. doi:10.1007/s10620-015-3607-y
  • Liu Y, Zhang L, Wang X, Wang Z, Zhang J, Jiang R, et al. Similar fecal microbiota signatures in patients with diarrhea-predominant irritable bowel syndrome and patients with depression. Clin Gastroenterol Hepatol. 2016;14(11):1602–11. e1605. doi:10.1016/j.cgh.2016.05.033
  • Zhong W, Lu X, Shi H, Zhao G, Song Y, Wang Y, et al. Distinct microbial populations exist in the mucosa-associated microbiota of diarrhea predominant irritable bowel syndrome and ulcerative colitis. J Clin Gastroenterol. 2019;53(9):660–72. doi:10.1097/MCG.0000000000000961
  • Chakraborti A, Graham C, Chehade S, Vashi B, Umfress A, Kurup P, et al. High fructose corn syrup-moderate fat diet potentiates anxio-depressive behavior and alters ventral striatal neuronal signaling. Front Neurosci. 2021;15:669410. doi:10.3389/fnins.2021.669410
  • Ye J, Lee JW, Presley LL, Bent E, Wei B, Braun J, et al. Bacteria and bacterial rRNA genes associated with the development of colitis in IL-10−/− mice. Inflamm Bowel Dis. 2008;14(8):1041–50. doi:10.1002/ibd.20442
  • Dallman MF, Akana SF, Laugero KD, Gomez F, Manalo S, Bell ME, Bhatnagar S. A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress. Physiol Behav. 2003;79(1):3–12. doi:10.1016/S0031-9384(03)00100-8
  • Wilson ME, Fisher J, Fischer A, Lee V, Harris RB, Bartness TJ. Quantifying food intake in socially housed monkeys: social status effects on caloric consumption. Physiol Behav. 2008;94(4):586–94. doi:10.1016/j.physbeh.2008.03.019
  • Raspopow K, Abizaid A, Matheson K, Anisman H. Psychosocial stressor effects on cortisol and ghrelin in emotional and non-emotional eaters: influence of anger and shame. Horm Behav. 2010;58(4):677–84. doi:10.1016/j.yhbeh.2010.06.003
  • Kaiser B, Gemesi K, Holzmann SL, Wintergerst M, Lurz M, Hauner H, et al. Stress-induced hyperphagia: empirical characterization of stress-overeaters. BMC Public Health. 2022;22(1):100. doi:10.1186/s12889-021-12488-9
  • Ganley RM. Emotion and eating in obesity: a review of the literature. Int J Eating Disord. 1989;8:343–61. doi:10.1002/1098-108X(198905)8:3<343::AID-EAT2260080310>3.0.CO;2-C.
  • Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34(1):13–25. doi:10.1016/S0896-6273(02)00653-0
  • Bazhan N, Zelena D. Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis. Brain Res Bull. 2013;95:46–53. doi:10.1016/j.brainresbull.2013.04.002
  • Clauss N, Byrd-Craven J. Exposure to a sex-specific stressor mitigates sex differences in stress-induced eating. Physiol Behav. 2019;202:26–35. doi:10.1016/j.physbeh.2019.01.017
  • Maniam J, Morris MJ. The link between stress and feeding behaviour. Neuropharmacology. 2012;63(1):97–110. doi:10.1016/j.neuropharm.2012.04.017
  • Elman I, Borsook D. Common brain mechanisms of chronic pain and addiction. Neuron. 2016;89(1):11–36. doi:10.1016/j.neuron.2015.11.027
  • Lin Y, De Araujo I, Stanley G, Small D, Geha P. Chronic pain precedes disrupted eating behavior in low-back pain patients. PLOS ONE. 2022;17(2):e0263527.
  • Geha P, deAraujo I, Green B, Small DM. Decreased food pleasure and disrupted satiety signals in chronic low back pain. PAIN. 2014;155(4):712–22. doi:10.1016/j.pain.2013.12.027.
  • Wegierska AE, Charitos IA, Topi S, Potenza MA, Montagnani M, Santacroce L. The connection between physical exercise and gut microbiota: implications for competitive sports athletes. Sports Med. 2022;52(10):2355–69. doi:10.1007/s40279-022-01696-x
  • Pianucci L, Sonagra M, Greenberg BA, Priestley DR, Gmuca S. Disordered eating among adolescents with chronic pain: the experience of a pediatric rheumatology subspecialty pain clinic. Pediat Rheumatol. 2021;19(1):16. doi:10.1186/s12969-021-00506-4
  • Alhadeff AL, Su Z, Hernandez E, Klima ML, Phillips SZ, Holland RA, et al. A neural circuit for the suppression of pain by a competing need state. Cell. 2018;173(1):140–52. e115. doi:10.1016/j.cell.2018.02.057
  • Tang H-D, Dong W-Y, Hu R, Huang J-Y, Huang Z-H, Xiong W, et al. A neural circuit for the suppression of feeding under persistent pain. Nat Metabol. 2022;4(12):1746–55. doi:10.1038/s42255-022-00688-5.
  • O'Sullivan O, Cronin O, Clarke SF, Murphy EF, Molloy MG, Shanahan F, Cotter PD. Exercise and the microbiota. Gut Microbes. 2015;6(2):131–6. doi:10.1080/19490976.2015.1011875
  • Allen JM, Mailing LJ, Niemiro GM, Moore R, Cook MD, White BA, et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018;50(4):747–57. doi:10.1249/MSS.0000000000001495
  • Klingbeil E, de La Serre CB. Microbiota modulation by eating patterns and diet composition: impact on food intake. Am J Physiol Regul Integr Comp Physiol. 2018;315(6):R1254–r1260. doi:10.1152/ajpregu.00037.2018
  • Sen P, Molinero-Perez A, O'Riordan KJ, McCafferty CP, O'Halloran KD, Cryan JF. Microbiota and sleep: awakening the gut feeling. Trends Mol Med. 2021;27(10):935–45. doi:10.1016/j.molmed.2021.07.004
  • Boscaini S, Leigh SJ, Lavelle A, García-Cabrerizo R, Lipuma T, Clarke G, et al. Microbiota and body weight control: weight watchers within? Mol Metab. 2022;57:101427. doi:10.1016/j.molmet.2021.101427
  • Paine P. Current and future treatment approaches for pain in IBS. Aliment Pharmacol Ther. 2021;54:S75–S88. doi:10.1111/apt.16550
  • Bootz-Maoz H, Pearl A, Melzer E, Malnick S, Sharon E, Bennet Y, et al. Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome. Cell Rep. 2022;41(7):111657. doi:10.1016/j.celrep.2022.111657
  • Davidson JR. Pharmacologic treatment of acute and chronic stress following trauma: 2006. J Clin Psychiatry. 2006;67(Suppl 2):34–9.
  • Shapiro F. The role of eye movement desensitization and reprocessing (EMDR) therapy in medicine: addressing the psychological and physical symptoms stemming from adverse life experiences. Perm J. 2014;18(1):71–7. doi:10.7812/TPP/13-098
  • Nakao M, Shirotsuki K, Sugaya N. Cognitive-behavioral therapy for management of mental health and stress-related disorders: recent advances in techniques and technologies. Biopsychosoc Med. 2021;15(1):16. doi:10.1186/s13030-021-00219-w
  • Pierce P, Xie G-X, Levine J, Peroutka S. 5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: a polymerase chain reaction study. Neuroscience. 1996;70(2):553–9. doi:10.1016/0306-4522(95)00329-0
  • Neubert MJ, Kincaid W, Heinricher MM. Nociceptive facilitating neurons in the rostral ventromedial medulla. Pain. 2004;110(1-2):158–65. doi:10.1016/j.pain.2004.03.017
  • Roth W, Zadeh K, Vekariya R, Ge Y, Mohamadzadeh M. Tryptophan metabolism and gut-brain homeostasis. Int J Mol Sci. 2021;22(6):2973. doi:10.3390/ijms22062973.
  • Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012;13(10):701–12. doi:10.1038/nrn3346
  • Dehhaghi M, Kazemi Shariat Panahi H, Guillemin GJ. Microorganisms, tryptophan metabolism, and kynurenine pathway: a complex interconnected loop influencing human health status. Int J Tryptophan Res. 2019;12:1178646919852996. doi:10.1177/1178646919852996
  • Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpé S, Maes M. IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry. 2005;10(6):538–44. doi:10.1038/sj.mp.4001600
  • Li CC, Jiang N, Gan L, Zhao MJ, Chang Q, Liu XM, Pan RL. Peripheral and cerebral abnormalities of the tryptophan metabolism in the depression-like rats induced by chronic unpredicted mild stress. Neurochem Int. 2020;138:104771. doi:10.1016/j.neuint.2020.104771
  • Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43(2):164–74. doi:10.1016/j.jpsychires.2008.03.009
  • Hayashida K-I, Obata H, Nakajima K, Eisenach JC. Gabapentin acts within the locus coeruleus to alleviate neuropathic pain. J Am Soc Anesthesiol. 2008;109(6):1077–84.
  • Calvo M, Bennett DL. The mechanisms of microgliosis and pain following peripheral nerve injury. Exp Neurol. 2012;234(2):271–82. doi:10.1016/j.expneurol.2011.08.018
  • Asgharieh-Ahari M, Tamaddonfard E, Erfanparast A, Soltanalinejad-Taghiabad F. Histamine and its H1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors. Behav Pharmacol. 2023;34(8):457–67. doi:10.1097/FBP.0000000000000724.
  • Kaur G, Singh N, Jaggi AS. Mast cells in neuropathic pain: an increasing spectrum of their involvement in pathophysiology. Rev Neurosci. 2017;28(7):759–66. doi:10.1515/revneuro-2017-0007
  • Obara I, Telezhkin V, Alrashdi I, Chazot PL. Histamine, histamine receptors, and neuropathic pain relief. Br J Pharmacol. 2020;177(3):580–99. doi:10.1111/bph.14696
  • Micheli L, Durante M, Lucarini E, Sgambellone S, Lucarini L, Di Cesare Mannelli L, et al. The histamine H(4) receptor participates in the anti-neuropathic effect of the adenosine A(3) receptor agonist IB-MECA: role of CD4(+) T cells. Biomolecules. 2021;11(10). doi:10.3390/biom11101447
  • Micheli L, Lucarini E, Nobili S, Bartolucci G, Pallecchi M, Toti A, et al. Ultramicronized N-palmitoylethanolamine contributes to morphine efficacy against neuropathic pain: implication of mast cells and glia. Curr Neuropharmacol. 2022;22(1):88–106. doi:10.2174/1570159X21666221128091453.
  • Toti A, Micheli L, Lucarini E, Ferrara V, Ciampi C, Margiotta F, et al. Ultramicronized N-palmitoylethanolamine regulates mast cell-astrocyte crosstalk: a new potential mechanism underlying the inhibition of morphine tolerance. Biomolecules. 2023;13(2). doi:10.3390/biom13020233
  • Delvalle NM, Dharshika C, Morales-Soto W, Fried DE, Gaudette L, Gulbransen BD. Communication between enteric neurons, glia, and nociceptors underlies the effects of tachykinins on neuroinflammation. Cell Mol Gastroenterol Hepatol. 2018;6(3):321–44. doi:10.1016/j.jcmgh.2018.05.009
  • Hasler WL, Grabauskas G, Singh P, Owyang C. Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome. Neurogastroenterol Motil. 2022;34(7):e14339. doi:10.1111/nmo.14339
  • Vicentini FA, Keenan CM, Wallace LE, Woods C, Cavin JB, Flockton AR, et al. Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia. Microbiome. 2021;9(1):210. doi:10.1186/s40168-021-01165-z
  • Haxhiu MA, Tolentino-Silva F, Pete G, Kc P, Mack SO. Monoaminergic neurons, chemosensation and arousal. Respir Physiol. 2001;129(1-2):191–209. doi:10.1016/S0034-5687(01)00290-0
  • Taylor KM, Snyder SH. Histamine in rat brain: sensitive assay of endogenous levels, formation in vivo and lowering by inhibitors of histidine decarboxylase. J Pharmacol Exp Ther. 1971;179(3):619–33.
  • Endou M, Yanai K, Sakurai E, Fukudo S, Hongo M, Watanabe T. Food-deprived activity stress decreased the activity of the histaminergic neuron system in rats. Brain Res. 2001;891(1-2):32–41. doi:10.1016/S0006-8993(00)03226-1
  • Rani B, Santangelo A, Romano A, Koczwara JB, Friuli M, Provensi G, et al. Brain histamine and oleoylethanolamide restore behavioral deficits induced by chronic social defeat stress in mice. Neurobiol Stress. 2021;14:100317. doi:10.1016/j.ynstr.2021.100317
  • Thomas CM, Hong T, van Pijkeren JP, Hemarajata P, Trinh DV, Hu W, et al. Histamine derived from probiotic lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PLoS One. 2012;7(2):e31951. doi:10.1371/journal.pone.0031951
  • Russo R, Cristiano C, Avagliano C, De Caro C, La Rana G, Raso GM, et al. Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem. 2018;25(32):3930–52. doi:10.2174/0929867324666170216113756
  • Petitfils C, Maurel S, Payros G, Hueber A, Agaiz B, Gazzo G, et al. Identification of bacterial lipopeptides as key players in IBS. Gut. 2022;72(5):939–950. doi:10.1136/gutjnl-2022-328084.
  • Oh SF, Praveena T, Song H, Yoo JS, Jung DJ, Erturk-Hasdemir D, et al. Host immunomodulatory lipids created by symbionts from dietary amino acids. Nature. 2021;600(7888):302–7. doi:10.1038/s41586-021-04083-0
  • Ji R-R, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology. 2018;129(2):343–66. doi:10.1097/ALN.0000000000002130
  • Lang-Illievich K, Klivinyi C, Lasser C, Brenna CTA, Szilagyi IS, Bornemann-Cimenti H. Palmitoylethanolamide in the treatment of chronic pain: a systematic review and meta-analysis of double-blind randomized controlled trials. Nutrients. 2023;15(6):1350. doi:10.3390/nu15061350
  • Fu J, Astarita G, Gaetani S, Kim J, Cravatt BF, Mackie K, Piomelli D. Food intake regulates oleoylethanolamide formation and degradation in the proximal small intestine. J Biol Chem. 2007;282(2):1518–28. doi:10.1074/jbc.M607809200
  • Foster JA, Rinaman L, Cryan JF. Stress & the gut-brain axis: regulation by the microbiome. Neurobiol Stress. 2017;7:124–36. doi:10.1016/j.ynstr.2017.03.001
  • Winter G, Hart RA, Charlesworth RPG, Sharpley CF. Gut microbiome and depression: what we know and what we need to know. Rev Neurosci. 2018;29(6):629–43. doi:10.1515/revneuro-2017-0072
  • Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CSM. The gut microbiota in anxiety and depression - a systematic review. Clin Psychol Rev. 2021;83:101943. doi:10.1016/j.cpr.2020.101943
  • Jin P, Yu HL, Tian-Lan, Zhang F, Quan ZS. Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress. Pharmacol Biochem Behav. 2015;133:146–54. doi:10.1016/j.pbb.2015.04.001
  • Li M, Wang D, Bi W, Jiang ZE, Piao R, Yu H. -Palmitoylethanolamide Exerts antidepressant-like effects in rats: involvement of PPAR. J Pharmacol Exp Ther. 2019a;369(1):163–72. doi:10.1124/jpet.118.254524
  • Hill MN, Miller GE, Carrier EJ, Gorzalka BB, Hillard CJ. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 2009;34(8):1257–62. doi:10.1016/j.psyneuen.2009.03.013
  • Suardíaz M, Estivill-Torrús G, Goicoechea C, Bilbao A, Rodríguez de Fonseca F. Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain. Pain. 2007;133(1-3):99–110. doi:10.1016/j.pain.2007.03.008
  • Rodríguez de Fonseca F, Navarro M, Gómez R, Escuredo L, Nava F, Fu J, et al. An anorexic lipid mediator regulated by feeding. Nature. 2001;414(6860):209–12. doi:10.1038/35102582
  • Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez De Fonseca F, et al. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature. 2003;425(6953):90–3. doi:10.1038/nature01921
  • Fu J, Oveisi F, Gaetani S, Lin E, Piomelli D. Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology. 2005;48(8):1147–53. doi:10.1016/j.neuropharm.2005.02.013
  • Lo Verme J, Fu J, Astarita G, La Rana G, Russo R, Calignano A, Piomelli D. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol. 2005a;67(1):15–9. doi:10.1124/mol.104.006353
  • Lo Verme J, Gaetani S, Fu J, Oveisi F, Burton K, Piomelli D. Regulation of food intake by oleoylethanolamide. Cell Mol Life Sci. 2005b;62(6):708–16. doi:10.1007/s00018-004-4494-0
  • Paterniti I, Impellizzeri D, Crupi R, Morabito R, Campolo M, Esposito E, Cuzzocrea S. Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma. J Neuroinflammation. 2013;10:20.
  • Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 2006;3(3):167–75. doi:10.1016/j.cmet.2006.02.004
  • Almási R, Szoke E, Bölcskei K, Varga A, Riedl Z, Sándor Z, et al. Actions of 3-methyl-N-oleoyldopamine, 4-methyl-N-oleoyldopamine and N-oleoylethanolamide on the rat TRPV1 receptor in vitro and in vivo. Life Sci. 2008;82(11-12):644–51. doi:10.1016/j.lfs.2007.12.022
  • Godlewski G, Offertáler L, Wagner JA, Kunos G. Receptors for acylethanolamides-GPR55 and GPR119. Prostaglandins Other Lipid Mediat. 2009;89(3-4):105–11. doi:10.1016/j.prostaglandins.2009.07.001
  • Di Cesare Mannelli L, Corti F, Micheli L, Zanardelli M, Ghelardini C. Delay of morphine tolerance by palmitoylethanolamide. BioMed Res Int. 2015;2015:894732. doi:10.1155/2015/894732.
  • Di Cesare Mannelli L, Micheli L, Lucarini E, Ghelardini C. Ultramicronized N-palmitoylethanolamine supplementation for long-lasting, low-dosed morphine antinociception. Front Pharmacol. 2018;9:473. doi:10.3389/fphar.2018.00473
  • Micheli L, Lucarini E, Toti A, Ferrara V, Ciampi C, Parisio C, et al. Effects of ultramicronized N-palmitoylethanolamine supplementation on tramadol and oxycodone analgesia and tolerance prevention. Pharmaceutics. 2022b;14(2):403. doi:10.3390/pharmaceutics14020403
  • Keppel Hesselink J. Professor Rita Levi-Montalcini on nerve growth factor, mast cells and palmitoylethanolamide, an endogenous anti-inflammatory and analgesic compound. J Pain Relief. 2013;2(114):2167–0846.1000.
  • D’Antongiovanni V, Pellegrini C, Antonioli L, Benvenuti L, Di Salvo C, Flori L, et al. Palmitoylethanolamide counteracts enteric inflammation and bowel motor dysfunctions in a mouse model of Alzheimer’s disease. Front Pharmacol. 2021;12:748021. doi:10.3389/fphar.2021.748021.
  • Boeckxstaens GE. The emerging role of mast cells in irritable bowel syndrome. Gastroenterol Hepatol (N Y). 2018;14(4):250.
  • Lucarini E, Seguella L, Vincenzi M, Parisio C, Micheli L, Toti A, et al. Role of enteric glia as bridging element between Gut inflammation and visceral pain consolidation during acute colitis in rats. Biomedicines. 2021;9(11):1671. doi:10.3390/biomedicines9111671.
  • Fichna J, Wood JT, Papanastasiou M, Vadivel SK, Oprocha P, Sałaga M, et al. Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study. PLoS One. 2013;8(12):e85073. doi:10.1371/journal.pone.0085073
  • Brierley SM, Greenwood-Van Meerveld B, Sarnelli G, Sharkey KA, Storr M, Tack J. Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome. Nat Rev Gastroenterol Hepatol. 2023;20(1):5–25. doi:10.1038/s41575-022-00682-y
  • Schiano Moriello A, Di Marzo V, Petrosino S. Mutual links between the endocannabinoidome and the gut microbiome, with special reference to companion animals: a nutritional viewpoint. Animals. 2022;12(3):348. doi:10.3390/ani12030348
  • De Couck M, Nijs J, Gidron Y. You may need a nerve to treat pain: the neurobiological rationale for vagal nerve activation in pain management. Clin J Pain. 2014;30(12):1099–105. doi:10.1097/AJP.0000000000000071
  • Jia W, Xie G, Jia W. Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018;15(2):111–28. doi:10.1038/nrgastro.2017.119
  • Minerbi A, Gonzalez E, Brereton N, Fitzcharles M-A, Chevalier S, Shir Y. Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity. PAIN. 2023;164(2):e66–76. doi:10.1097/j.pain.0000000000002694.
  • Gottesman-Katz L, Latorre R, Vanner S, Schmidt BL, Bunnett NW. Targeting G protein-coupled receptors for the treatment of chronic pain in the digestive system. Gut. 2021;70(5):970–81. doi:10.1136/gutjnl-2020-321193
  • Ni Dhonnabhain R, Xiao Q, O’Malley D. Aberrant gut-to-brain signaling in irritable bowel syndrome-the role of bile acids. Front Endocrinol. 2021;12:745190. doi:10.3389/fendo.2021.745190.
  • Ocvirk S, O’Keefe SJD. Dietary fat, bile acid metabolism and colorectal cancer. Semin Cancer Biol. 2021;73:347–55. doi:10.1016/j.semcancer.2020.10.003
  • Alessandri JM, Guesnet P, Vancassel S, Astorg P, Denis I, Langelier B, et al. Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. Reprod Nutr Dev. 2004;44(6):509–38. doi:10.1051/rnd:2004063
  • Hennebelle M, Champeil-Potokar G, Lavialle M, Vancassel S, Denis I. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus. Nutr Rev. 2014;72(2):99–112. doi:10.1111/nure.12088
  • Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186–94. doi:10.1016/j.bbi.2015.03.016
  • Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79. doi:10.1186/gb-2012-13-9-r79
  • Carballo-Casla A, García-Esquinas E, Banegas JR, Rodríguez-Artalejo F, Ortolá R. Fish consumption, omega-3 fatty acid intake, and risk of pain: the seniors-ENRICA-1 cohort. Clin Nutr. 2022;41(11):2587–95. doi:10.1016/j.clnu.2022.09.007
  • Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007;129(1):210–23. doi:10.1016/j.pain.2007.01.020
  • Silva RV, Oliveira JT, Santos BLR, Dias FC, Martinez AMB, Lima CKF, etal Long-chain omega-3 fatty acids supplementation accelerates nerve regeneration and prevents neuropathic pain behavior in mice. Front Pharmacol. 2017;8:723. doi:10.3389/fphar.2017.00723.
  • Zhang E, Kim J-J, Shin N, Yin Y, Nan Y, Xu Y, et al. High omega-3 polyunsaturated fatty acids in fat-1 mice reduce inflammatory pain. J Med Food. 2017;20(6):535–41. doi:10.1089/jmf.2016.3871
  • Unda SR, Villegas EA, Toledo ME, Asis Onell G, Laino CH. Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain. J Pharm Pharmacol. 2019;72(3):437–47. doi:10.1111/jphp.13213
  • de Oliveira Galassi T, Fernandes PF, Salgado ASI, Cidral-Filho FJ, Piovezan AP, Lüdtke DD, et al. Preventive supplementation of omega-3 reduces pain and pro-inflammatory cytokines in a mouse model of complex regional pain syndrome type I. Front Integr Neurosci. 2022;16:840249. doi:10.3389/fnint.2022.840249.
  • Lucarini E, Micheli L, Pagnotta E, Toti A, Ferrara V, Ciampi C, et al. The efficacy of camelina sativa defatted seed meal against colitis-induced persistent visceral hypersensitivity: the relevance of PPAR α receptor activation in pain relief. Nutrients. 2022;14(15):3137. doi:10.3390/nu14153137.
  • MacIntosh-Smith W, Abdallah A, Cunningham C. The potential effects of polyunsaturated ω-3 fatty acids on spinal cord injury: a systematic review & meta-analysis of preclinical evidence. Prostaglandins, Leukotrienes Essent Fatty Acids. 2023;191:102554. doi:10.1016/j.plefa.2023.102554.
  • Lamberg-Allardt C. Vitamin D in foods and as supplements. Prog Biophys Mol Biol. 2006;92(1):33–8. doi:10.1016/j.pbiomolbio.2006.02.017
  • Jamilian H, Amirani E, Milajerdi A, Kolahdooz F, Mirzaei H, Zaroudi M, et al. The effects of vitamin D supplementation on mental health, and biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: a systematic review and meta-analysis of randomized controlled trials. Prog Neuropsychopharmacol Biol Psychiatry. 2019;94:109651. doi:10.1016/j.pnpbp.2019.109651
  • Lim W-C, Hanauer SB, Li YC. Mechanisms of disease: vitamin D and inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol. 2005;2(7):308–15. doi:10.1038/ncpgasthep0215
  • Jin D, Wu S, Zhang Y-G, Lu R, Xia Y, Dong H, Sun J. Lack of vitamin D receptor causes dysbiosis and changes the functions of the murine intestinal microbiome. Clin Ther. 2015a;37(5):996–1009. e1007. doi:10.1016/j.clinthera.2015.04.004
  • Su D, Nie Y, Zhu A, Chen Z, Wu P, Zhang L, et al. Vitamin D signaling through induction of Paneth cell defensins maintains gut microbiota and improves metabolic disorders and hepatic steatosis in animal models. Front Physiol. 2016;7:498.
  • Shang M, Sun J. Vitamin D/VDR, probiotics, and gastrointestinal diseases. Curr Med Chem. 2017;24(9):876–87. doi:10.2174/0929867323666161202150008
  • Akyuz G, Sanal-Toprak C, Yagci I, Giray E, Kuru-Bektasoglu P. The effect of vitamin D supplementation on pain, quality of life, and nerve conduction studies in women with chronic widespread pain. Int J Rehabil Res. 2017;40(1):76–83. doi:10.1097/MRR.0000000000000211
  • Zadro J, Shirley D, Ferreira M, Carvalho-Silva A, Lamb S, Cooper C, etal Mapping the association between vitamin D and low back pain: a systematic review and meta-analysis of observational studies. Pain Phys. 2017;20(7):611–40.
  • O’Mahony L, Stepien M, Gibney MJ, Nugent AP, Brennan L. The potential role of vitamin D enhanced foods in improving vitamin D status. Nutrients. 2011;3(12):1023–41. doi:10.3390/nu3121023
  • Sedaghat K, Yousefian Z, Vafaei AA, Rashidy-Pour A, Parsaei H, Khaleghian A, Choobdar S. Mesolimbic dopamine system and its modulation by vitamin D in a chronic mild stress model of depression in the rat. Behav Brain Res. 2019;356:156–69. doi:10.1016/j.bbr.2018.08.020
  • Bakhtiari-Dovvombaygi H, Izadi S, Zare M, Asgari Hassanlouei E, Dinpanah H, Ahmadi-Soleimani SM, Beheshti F. Vitamin D3 administration prevents memory deficit and alteration of biochemical parameters induced by unpredictable chronic mild stress in rats. Sci Rep. 2021a;11(1):16271. doi:10.1038/s41598-021-95850-6
  • Bakhtiari-Dovvombaygi H, Izadi S, Zare Moghaddam M, Hashemzehi M, Hosseini M, Azhdari-Zarmehri H, et al. Beneficial effects of vitamin D on anxiety and depression-like behaviors induced by unpredictable chronic mild stress by suppression of brain oxidative stress and neuroinflammation in rats. Naunyn Schmiedebergs Arch Pharmacol. 2021b;394(4):655–67. doi:10.1007/s00210-020-02002-0
  • Sedaghat K, Naderian R, Pakdel R, Bandegi AR, Ghods Z. Regulatory effect of vitamin D on pro-inflammatory cytokines and anti-oxidative enzymes dysregulations due to chronic mild stress in the rat hippocampus and prefrontal cortical area. Mol Biol Rep. 2021;48(12):7865–73. doi:10.1007/s11033-021-06810-2
  • Guo Y, Xie JP, Deng K, Li X, Yuan Y, Xuan Q, et al. Prophylactic effects of bifidobacterium adolescentis on anxiety and depression-like phenotypes after chronic stress: a role of the Gut microbiota-inflammation axis. Front Behav Neurosci. 2019b;13:126. doi:10.3389/fnbeh.2019.00126
  • Singh P, Rawat A, Alwakeel M, Sharif E, Al Khodor S. The potential role of vitamin D supplementation as a gut microbiota modifier in healthy individuals. Sci Rep. 2020;10(1):21641. doi:10.1038/s41598-020-77806-4
  • Gonzalez MJ, Miranda-Massari JR. Diet and stress. Psychiatr Clin North Am. 2014;37(4):579–89. doi:10.1016/j.psc.2014.08.004
  • Jomova K, Valko M. Health protective effects of carotenoids and their interactions with other biological antioxidants. Eur J Med Chem. 2013;70:102–10. doi:10.1016/j.ejmech.2013.09.054
  • Feng Y, Yu Y, Chen Z, Wang L, Ma J, Bai X, et al. Effects of β-carotin and green tea powder diets on alleviating the symptoms of gouty arthritis and improving gut microbiota in C57BL/6 mice. Front Microbiol. 2022;13:837182. doi:10.3389/fmicb.2022.837182
  • Kuo C-F, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol. 2015;11(11):649–62. doi:10.1038/nrrheum.2015.91
  • Chiaro TR, Soto R, Zac Stephens W, Kubinak JL, Petersen C, Gogokhia L, et al. A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med. 2017;9(380):eaaf9044. doi:10.1126/scitranslmed.aaf9044
  • Luongo L, Guida F, Maione S, Jacobson KA, Salvemini D. Adenosine metabotropic receptors in chronic pain management. Front Pharmacol. 2021;12:651038. doi:10.3389/fphar.2021.651038.
  • Mars RAT, Yang Y, Ward T, Houtti M, Priya S, Lekatz HR, et al. Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome. Cell. 2020;183(4):1137–40. doi:10.1016/j.cell.2020.10.040
  • Guillemot-Legris O, Masquelier J, Everard A, Cani PD, Alhouayek M, Muccioli GG. High-fat diet feeding differentially affects the development of inflammation in the central nervous system. J Neuroinflammation. 2016;13(1):206. doi:10.1186/s12974-016-0666-8
  • Saiyasit N, Chunchai T, Prus D, Suparan K, Pittayapong P, Apaijai N, et al. Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition. Nutrition. 2020;69:110576. doi:10.1016/j.nut.2019.110576
  • Wu H, Zhang W, Huang M, Lin X, Chiou J. Prolonged high-fat diet consumption throughout adulthood in mice induced neurobehavioral deterioration via gut-brain axis. Nutrients. 2023;15(2):392. doi:10.3390/nu15020392.
  • Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on body function: a review. EXCLI J. 2017;16:1057–72.
  • Tsai SF, Wu HT, Chen PC, Chen YW, Yu M, Tzeng SF, et al. Stress aggravates high-fat-diet-induced insulin resistance via a mechanism that involves the amygdala and is associated with changes in neuroplasticity. Neuroendocrinology. 2018;107(2):147–57. doi:10.1159/000491018
  • Wang W, Yang J, Xu J, Yu H, Liu Y, Wang R, et al. Effects of high-fat diet and chronic mild stress on depression-like behaviors and levels of inflammatory cytokines in the hippocampus and prefrontal cortex of rats. Neuroscience. 2022b;480:178–93. doi:10.1016/j.neuroscience.2021.11.015
  • Buwalda B, Blom WA, Koolhaas JM, van Dijk G. Behavioral and physiological responses to stress are affected by high-fat feeding in male rats. Physiol Behav. 2001;73(3):371–7. doi:10.1016/S0031-9384(01)00493-0
  • Jene T, Ruiz de Azua I, Hasch A, Klüpfel J, Deuster J, Maas M, et al. Chronic social stress lessens the metabolic effects induced by a high-fat diet. J Endocrinol. 2021;249(1):19–30. doi:10.1530/JOE-20-0633
  • MacKay JC, Kent P, James JS, Cayer C, Merali Z. Ability of palatable food consumption to buffer against the short- and long-term behavioral consequences of social defeat exposure during juvenility in rats. Physiol Behav. 2017;177:113–21. doi:10.1016/j.physbeh.2017.04.002
  • Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, etal The firmicutes/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients? Nutrients. 2020;12(5):1474. doi:10.3390/nu12051474.
  • Bridgewater LC, Zhang C, Wu Y, Hu W, Zhang Q, Wang J, et al. Gender-based differences in host behavior and gut microbiota composition in response to high fat diet and stress in a mouse model. Sci Rep. 2017;7(1):10776. doi:10.1038/s41598-017-11069-4
  • Marques Miranda C, de Lima Campos M, Leite-Almeida H. Diet, body weight and pain susceptibility – a systematic review of preclinical studies. Neurobiology of Pain. 2021;10:100066. doi:10.1016/j.ynpai.2021.100066
  • Liu J, Wong SCS. Molecular mechanisms and pathophysiological pathways of high-fat diets and caloric restriction dietary patterns on pain. Anesth Analg. 2023;137(1):137–52. doi:10.1213/ANE.0000000000006289.
  • Herman RM, Brower JB, Stoddard DG, Casano AR, Targovnik JH, Herman JH, Tearse P. Prevalence of somatic small fiber neuropathy in obesity. Int J Obes. 2007;31(2):226–35. doi:10.1038/sj.ijo.0803418
  • Callaghan BC, Gao L, Li Y, Zhou X, Reynolds E, Banerjee M, et al. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy. Ann Clin Transl Neurol. 2018;5(4):397–405. doi:10.1002/acn3.531
  • Nyavor Y, Brands CR, May G, Kuther S, Nicholson J, Tiger K, et al. High-fat diet–induced alterations to gut microbiota and gut-derived lipoteichoic acid contributes to the development of enteric neuropathy. Neurogastroenterol Motil. 2020;32(7):e13838. doi:10.1111/nmo.13838
  • Guo K, Figueroa-Romero C, Noureldein M, Hinder LM, Sakowski SA, Rumora AE, et al. Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics. Microbiome. 2023;11(1):52. doi:10.1186/s40168-022-01436-3
  • Apkarian AV, Neugebauer V, Koob G, Edwards S, Levine JD, Ferrari L, et al. Neural mechanisms of pain and alcohol dependence. Pharmacol Biochem Behav. 2013;112:34–41. doi:10.1016/j.pbb.2013.09.008
  • Maleki N, Tahaney K, Thompson BL, Oscar-Berman M. At the intersection of alcohol use disorder and chronic pain. Neuropsychology. 2019;33(6):795. doi:10.1037/neu0000558
  • Brown RA, Cutter HS. Alcohol, customary drinking behavior, and pain. J Abnorm Psychol. 1977;86(2):179. doi:10.1037/0021-843X.86.2.179
  • Jochum T, Boettger MK, Burkhardt C, Juckel G, Bär K-J. Increased pain sensitivity in alcohol withdrawal syndrome. Eur J Pain. 2010;14(7):713–8. doi:10.1016/j.ejpain.2009.11.008
  • You DS, Hahn HA, Welsh Jr TH, Meagher MW. Hyperalgesia after a drinking episode in young adult binge drinkers: a cross-sectional study. Alcohol Alcohol. 2020;55(6):608–15. doi:10.1093/alcalc/agaa035
  • Wang G, Liu Q, Guo L, Zeng H, Ding C, Zhang W, et al. Gut microbiota and relevant metabolites analysis in alcohol dependent mice. Front Microbiol. 2018;9:1874. doi:10.3389/fmicb.2018.01874
  • Mendes BG, Schnabl B. From intestinal dysbiosis to alcohol-associated liver disease. Clin Mol Hepatol. 2020;26(4):595. doi:10.3350/cmh.2020.0086
  • Gupta H, Suk KT, Kim DJ. Gut microbiota at the intersection of alcohol, brain, and the liver. J Clin Med. 2021;10(3):541. doi:10.3390/jcm10030541
  • Green PG, Alvarez P, Levine JD. Probiotics attenuate alcohol-induced muscle mechanical hyperalgesia: preliminary observations. Mol Pain. 2022;18:17448069221075345. doi:10.1177/17448069221075345
  • Banerjee N. Neurotransmitters in alcoholism: a review of neurobiological and genetic studies. Indian J Hum Genet. 2014;20(1):20–31. doi:10.4103/0971-6866.132750
  • Barandouzi ZA, Lee J, del Carmen Rosas M, Chen J, Henderson WA, Starkweather AR, Cong XS. Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome. Sci Rep. 2022;12(1):1648. doi:10.1038/s41598-022-05756-0
  • Becker HC, Lopez MF, Doremus-Fitzwater TL. Effects of stress on alcohol drinking: a review of animal studies. Psychopharmacology (Berl. 2011;218(1):131–56. doi:10.1007/s00213-011-2443-9
  • Gomez JL, Lewis MJ, Luine VN. The interaction of chronic restraint stress and voluntary alcohol intake: effects on spatial memory in male rats. Alcohol. 2012;46(5):499–504. doi:10.1016/j.alcohol.2011.12.005
  • Bahi A. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress. Stress. 2013;16(4):441–51. doi:10.3109/10253890.2012.754419
  • Higley JD, Hasert MF, Suomi SJ, Linnoila M. Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. Proc Natl Acad Sci USA. 1991;88(16):7261–5. doi:10.1073/pnas.88.16.7261
  • Rinninella E, Cintoni M, Raoul P, Gasbarrini A, Mele MC. Food additives, gut microbiota, and irritable bowel syndrome: a hidden track. Int J Environ Res Public Health. 2020;17(23):8816. doi:10.3390/ijerph17238816.
  • Palmnäs MS, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, et al. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PloS one. 2014;9(10):e109841. doi:10.1371/journal.pone.0109841
  • Wang Y-N, Meng X-C, Dong Y-F, Zhao X-H, Qian J-M, Wang H-Y, Li J-N. Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing. Chin Med J. 2019;132(15):1833–42. doi:10.1097/CM9.0000000000000308
  • Lucarini E, Di Pilato V, Parisio C, Micheli L, Toti A, Pacini A, et al. Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence. Pain. 2022a;163(5):861. doi:10.1097/j.pain.0000000000002438
  • Lowette K, Desmet AS, Farré RM, Tack J, Vanden Berghe P. Fructose consumption impairs serotonergic signaling in the murine enteric nervous system. Neurogastroenterol Motil. 2016;28(9):1438–42. doi:10.1111/nmo.12827
  • Ijssennagger N, van der Meer R, van Mil SWC. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med. 2016;22(3):190–9. doi:10.1016/j.molmed.2016.01.002
  • Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017;66(8):1414. doi:10.1136/gutjnl-2016-313099
  • Jiang Z, Zhao M, Zhang H, Li Y, Liu M, Feng F. Antimicrobial emulsifier–glycerol monolaurate induces metabolic syndrome, gut microbiota dysbiosis, and systemic low-grade inflammation in low-fat diet fed mice. Mol Nutr Food Res. 2018;62(3):1700547. doi:10.1002/mnfr.201700547
  • Furuhashi H, Higashiyama M, Okada Y, Kurihara C, Wada A, Horiuchi K, et al. Dietary emulsifier polysorbate-80-induced small-intestinal vulnerability to indomethacin-induced lesions via dysbiosis. J Gastroenterol Hepatol. 2020;35(1):110–7. doi:10.1111/jgh.14808
  • Pinget G, Tan J, Janac B, Kaakoush NO, Angelatos AS, O'Sullivan J, et al. Impact of the food additive titanium dioxide (E171) on gut microbiota-host interaction. Front Nutr. 2019;6:57. doi:10.3389/fnut.2019.00100.
  • Kwon YH, Banskota S, Wang H, Rossi L, Grondin JA, Syed SA, et al. Chronic exposure to synthetic food colorant Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice. Nat Commun. 2022;13(1):7617. doi:10.1038/s41467-022-35309-y
  • van Heel DA. Interleukin 15: its role in intestinal inflammation. Gut. 2006;55(4):444. doi:10.1136/gut.2005.079335
  • Hrncirova L, Machova V, Trckova E, Krejsek J, Hrncir T. Food preservatives induce proteobacteria dysbiosis in human-microbiota associated Nod2-deficient mice. Microorganisms. 2019;7(10):383. doi:10.3390/microorganisms7100383
  • Esquerre N, Basso L, Dubuquoy C, Djouina M, Chappard D, Blanpied C, et al. Aluminum ingestion promotes colorectal hypersensitivity in rodents. Cell Mol Gastroenterol Hepatol. 2019;7(1):185–96. doi:10.1016/j.jcmgh.2018.09.012
  • Helou C, Denis S, Spatz M, Marier D, Rame V, Alric M, et al. Insights into bread melanoidins: fate in the upper digestive tract and impact on the gut microbiota using in vitro systems. Food Funct. 2015;6(12):3737–45. doi:10.1039/C5FO00836K
  • Guerrero-Solano JA, Jaramillo-Morales OA, Velázquez-González C, De la OAM, Castañeda-Ovando A, Betanzos-Cabrera G, etal Pomegranate as a potential alternative of pain management: a review. Plants (Basel). 2020;9(4):419. doi:10.3390/plants9040419.
  • Haranishi Y, Hara K, Terada T. Analgesic potency of intrathecally administered punicalagin in rat neuropathic and inflammatory pain models. J Nat Med. 2022;76(1):314–20. doi:10.1007/s11418-021-01576-0
  • Jain V, Pareek A, Bhardwaj YR, Sinha SK, Gupta MM, Singh N. Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition. Nutr Neurosci. 2022;25(10):2149–66. doi:10.1080/1028415X.2021.1954293
  • Naveen S, Siddalingaswamy M, Singsit D, Khanum F. Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress. Psychiatry Clin Neurosci. 2013;67(7):501–8. doi:10.1111/pcn.12100
  • Hasan S, Suhail N, Bilal N, Ashraf GM, Zaidi SK, AlNohair S, Banu N. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway. Tumour Biol. 2016;37(5):5999–6006. doi:10.1007/s13277-015-4469-9
  • Parisio C, Lucarini E, Micheli L, Toti A, Khatib M, Mulinacci N, et al. Pomegranate mesocarp against colitis-induced visceral pain in rats: effects of a decoction and Its fractions. Int J Mol Sci. 2020;21(12):10423–35. doi:10.3390/ijms21124304.
  • Banc R, Rusu ME, Filip L, Popa DS. The impact of ellagitannins and their metabolites through Gut microbiome on the Gut health and brain wellness within the Gut-brain axis. Foods. 2023;12(2):270. doi:10.3390/foods12020270.
  • Parisio C, Lucarini E, Micheli L, Toti A, Bellumori M, Cecchi L, et al. Extra virgin olive oil and related by-products (Olea europaea L.) as natural sources of phenolic compounds for abdominal pain relief in gastrointestinal disorders in rats. Food Funct. 2020a;11(12):10423–35. doi:10.1039/D0FO02293D
  • Derry CJ, Derry S, Moore RA. Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database Syst Rev. 2014;2014(12):CD009281–CD009281.
  • Bagó-Mas A, Korimová A, Deulofeu M, Verdú E, Fiol N, Svobodová V, et al. Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice. Sci Rep. 2022;12(1):14980. doi:10.1038/s41598-022-19109-4
  • Soler-Martínez R, Deulofeu M, Bagó-Mas A, Dubový P, Verdú E, Fiol N, Boadas-Vaello P. Central neuropathic pain development modulation using coffee extract major polyphenolic compounds in spinal-cord-injured female mice. Biology. 2022;11(11):1617. doi:10.3390/biology11111617
  • De Feo M, Paladini A, Ferri C, Carducci A, Del Pinto R, Varrassi G, Grassi D. Anti-inflammatory and anti-nociceptive effects of cocoa: a review on future perspectives in treatment of pain. Pain Ther. 2020;9(1):231–40. doi:10.1007/s40122-020-00165-5
  • Machado M, Ferreira H, Oliveira M, Alves RC. Coffee by-products: an underexplored source of prebiotic ingredients. Crit Rev Food Sci Nutr. 2023;27:1–20.
  • Nehlig A. Effects of coffee on the gastro-intestinal tract: a narrative review and literature update. Nutrients. 2022;14(2):399. doi:10.3390/nu14020399.
  • Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010;9(3):318–30. doi:10.1016/S1474-4422(09)70290-X
  • Zis P, Sarrigiannis PG, Rao DG, Hadjivassiliou M. Gluten neuropathy: prevalence of neuropathic pain and the role of gluten-free diet. J Neurol. 2018;265(10):2231–6. doi:10.1007/s00415-018-8978-5
  • Marziali M, Venza M, Lazzaro S, Lazzaro A, Micossi C, Stolfi VM, Stolfi VM. Gluten-free diet: a new strategy for management of painful endometriosis related symptoms? Minerva Chir. 2012;67(6):499–504.
  • Marziali M, Capozzolo T. Role of gluten-free diet in the management of chronic pelvic pain of deep infiltranting endometriosis. J Minim Invasive Gynecol. 2015;22(6):S51–S52. doi:10.1016/j.jmig.2015.08.142
  • Isasi C, Stadnitsky A, Casco F, Tejerina E, Royuela A, Esteban B, Puga NF. Non-celiac gluten sensitivity and chronic refractory low back pain with spondyloarthritis features. Med Hypotheses. 2020;140:109646. doi:10.1016/j.mehy.2020.109646
  • Sharma N, Bhatia S, Chunduri V, Kaur S, Sharma S, Kapoor P, et al. Pathogenesis of celiac disease and other gluten related disorders in wheat and strategies for mitigating them. Front Nutr. 2020;7:6. doi:10.3389/fnut.2020.00006
  • Rodrigo L, Blanco I, Bobes J, de Serres FJ. Remarkable prevalence of coeliac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study. Arthritis Res Ther. 2013;15(6):1–12. doi:10.1186/ar4391
  • Dionne J, Ford AC, Yuan Y, Chey WD, Lacy BE, Saito YA, et al. A systematic review and meta-analysis evaluating the efficacy of a gluten-free diet and a low FODMAPs diet in treating symptoms of irritable bowel syndrome. Off J Am Coll Gastroenterol| ACG. 2018;113(9):1290–300.
  • Busby E, Bold J, Fellows L, Rostami K. Mood disorders and gluten: it's not all in your mind! a systematic review with meta-analysis. Nutrients. 2018;10(11):1708. doi:10.3390/nu10111708.
  • Wolf RL, Lebwohl B, Lee AR, Zybert P, Reilly NR, Cadenhead J, et al. Hypervigilance to a gluten-free diet and decreased quality of life in teenagers and adults with celiac disease. Dig Dis Sci. 2018;63(6):1438–48. doi:10.1007/s10620-018-4936-4
  • Caminero A, Galipeau HJ, McCarville JL, Johnston CW, Bernier SP, Russell AK, et al. Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity. Gastroenterology. 2016;151(4):670–83. doi:10.1053/j.gastro.2016.06.041
  • Constante M, Libertucci J, Galipeau HJ, Szamosi JC, Rueda G, Miranda PM, et al. Biogeographic variation and functional pathways of the gut microbiota in celiac disease. Gastroenterology. 2022;163(5):1351–63. e1315. doi:10.1053/j.gastro.2022.06.088
  • De Palma G, Reed DE, Bercik P. Diet-microbial cross-talk underlying increased visceral perception. Gut Microbes. 2023;15(1):2166780. doi:10.1080/19490976.2023.2166780
  • Berger B, Porta N, Foata F, Grathwohl D, Delley M, Moine D, et al. Linking human milk oligosaccharides, infant fecal community types, and later risk to require antibiotics. MBio. 2020;11(2):e03196–03119. doi:10.1128/mBio.03196-19
  • Gnoth MJ, Kunz C, Kinne-Saffran E, Rudloff S. Human milk oligosaccharides are minimally digested in vitro. J Nutr. 2000;130(12):3014–20. doi:10.1093/jn/130.12.3014
  • Davis JC, Totten SM, Huang JO, Nagshbandi S, Kirmiz N, Garrido DA, et al. Identification of oligosaccharides in feces of breast-fed infants and their correlation with the gut microbial community. Mol Cell Proteomics. 2016;15(9):2987–3002. doi:10.1074/mcp.M116.060665
  • Goehring KC, Kennedy AD, Prieto PA, Buck RH. Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants. PloS one. 2014;9(7):e101692. doi:10.1371/journal.pone.0101692
  • Tarr AJ, Galley JD, Fisher SE, Chichlowski M, Berg BM, Bailey MT. The prebiotics 3′ Sialyllactose and 6′ Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut–brain axis. Brain Behav Immun. 2015;50:166–77. doi:10.1016/j.bbi.2015.06.025
  • Foata F, Sprenger N, Rochat F, Damak S. Activation of the G-protein coupled receptor GPR35 by human milk oligosaccharides through different pathways. Sci Rep. 2020;10(1):16117. doi:10.1038/s41598-020-73008-0
  • Iribarren C, Törnblom H, Aziz I, Magnusson MK, Sundin J, Vigsnæs LK, et al. Human milk oligosaccharide supplementation in irritable bowel syndrome patients: a parallel, randomized, double-blind, placebo-controlled study. Neurogastroenterol Motil. 2020;32(10):e13920. doi:10.1111/nmo.13920
  • Palsson OS, Peery A, Seitzberg D, Amundsen ID, McConnell B, Simrén M. Human milk oligosaccharides support normal bowel function and improve symptoms of irritable bowel syndrome: a multicenter, open-label trial. Clin Transl Gastroenterol. 2020;11(12):e00276. doi:10.14309/ctg.0000000000000276.
  • Cavaletto M, Giuffrida MG, Conti A. Milk fat globule membrane components–a proteomic approach. Adv Exp Med Biol. 2008;606:129–41. doi:10.1007/978-0-387-74087-4_4
  • Hernell O, Timby N, Domellöf M, Lönnerdal B. Clinical benefits of milk fat globule membranes for infants and children. J Pediatr. 2016;173(Suppl):S60–65. doi:10.1016/j.jpeds.2016.02.077
  • O'Mahony SM, McVey Neufeld KA, Waworuntu RV, Pusceddu MM, Manurung S, Murphy K, et al. The enduring effects of early-life stress on the microbiota-gut-brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend. Eur J Neurosci. 2020;51(4):1042–58. doi:10.1111/ejn.14514
  • Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol. 2019;16(8):461–78. doi:10.1038/s41575-019-0157-3
  • Li S, Hua D, Wang Q, Yang L, Wang X, Luo A, Yang C. The role of bacteria and its derived metabolites in chronic pain and depression: recent findings and research progress. Int J Neuropsuchopharmacolog. 2019b;23(1):26–41. doi:10.1093/ijnp/pyz061
  • Jiang W, Wu J, Zhu S, Xin L, Yu C, Shen Z. The role of short chain fatty acids in irritable bowel syndrome. J Neurogastroenterol Motil. 2022;28(4):540–8. doi:10.5056/jnm22093
  • Li Z, Sun T, He Z, Li Z, Zhang W, Wang J, Xiang H. SCFAs ameliorate chronic postsurgical pain-related cognition dysfunction via the ACSS2-HDAC2 axis in rats. Mol Neurobiol. 2022;59(10):6211–27. doi:10.1007/s12035-022-02971-8
  • Tang Y, Du J, Wu H, Wang M, Liu S, Tao F. Potential therapeutic effects of short-chain fatty acids on chronic pain. Curr Neuropharmacol. 2022;22(2):191–203.
  • Kannampalli P, Shaker R, Sengupta JN. Colonic butyrate - algesic or analgesic? Neurogastroenterol Motil. 2011;23(11):975–9. doi:10.1111/j.1365-2982.2011.01775.x
  • Bonomo RR, Cook TM, Gavini CK, White CR, Jones JR, Bovo E, et al. Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice. Proc Natl Acad Sci USA. 2020;117(42):26482–93. doi:10.1073/pnas.2006065117
  • Lanza M, Filippone A, Ardizzone A, Casili G, Paterniti I, Esposito E, Campolo M. SCFA treatment alleviates pathological signs of migraine and related intestinal alterations in a mouse model of NTG-induced migraine. Cells. 2021;10(10):2756. doi:10.3390/cells10102756
  • Lanza M, Scuderi SA, Filippone A, Casili G, Campolo M, Paterniti I, et al. The role of SCFAs on microbiota composition in a mouse model of NTG-induced migraine. FASEB J. 2022;36. doi:10.1096/fasebj.2022.36.S1.R4645.
  • Esquerre N, Basso L, Defaye M, Vicentini FA, Cluny N, Bihan D, et al. Colitis-induced microbial perturbation promotes postinflammatory visceral hypersensitivity. Cell Mol Gastroenterol Hepatol. 2020;10(2):225–44. doi:10.1016/j.jcmgh.2020.04.003
  • Zhou F, Wang X, Han B, Tang X, Liu R, Ji Q, et al. Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization. Mol Pain. 2021;17:1744806921996520.
  • Caputi V, Bastiaanssen TF, Peterson V, Sajjad J, Simons LP, Murphy A, et al. Sex, pain, and the microbiome: the relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals. Brain Behav Immun. 2022;104:191–204. doi:10.1016/j.bbi.2022.06.002
  • van de Wouw M, Wang Y, Workentine ML, Vaghef-Mehrabani E, Dewey D, Reimer RA, et al. Associations between the gut microbiota and internalizing behaviors in preschool children. Psychosom Med. 2022;84(2):159–69. doi:10.1097/PSY.0000000000001026
  • Moayyedi P, Simrén M, Bercik P. Evidence-based and mechanistic insights into exclusion diets for IBS. Nature Reviews Gastroenterology & Hepatology. 2020;17(7):406–13. doi:10.1038/s41575-020-0270-3
  • Tuck CJ, Abu Omar A, De Palma G, Osman S, Jiménez-Vargas NN, Yu Y, et al. Changes in signalling from faecal neuroactive metabolites following dietary modulation of IBS pain. Gut. 2022:327260.
  • Cox SR, Lindsay JO, Fromentin S, Stagg AJ, McCarthy NE, Galleron N, et al. Effects of low FODMAP diet on symptoms, fecal microbiome, and markers of inflammation in patients with quiescent inflammatory bowel disease in a randomized trial. Gastroenterology. 2020;158(1):176–88.e177. doi:10.1053/j.gastro.2019.09.024
  • Han K, Nam J, Xu J, Sun X, Huang X, Animasahun O, et al. Generation of systemic antitumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel. Nat Biomed Eng. 2021;5(11):1377–88. doi:10.1038/s41551-021-00749-2
  • Boehme M, van de Wouw M, Bastiaanssen TFS, Olavarría-Ramírez L, Lyons K, Fouhy F, et al. Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Mol Psychiatry. 2020;25(10):2567–83. doi:10.1038/s41380-019-0425-1
  • Eswaran S, Dolan RD, Ball SC, Jackson K, Chey W. The impact of a 4-week low-FODMAP and mNICE diet on nutrient intake in a sample of US adults with irritable bowel syndrome with diarrhea. J Acad Nutr Diet. 2020;120(4):641–9. doi:10.1016/j.jand.2019.03.003
  • Staudacher HM, Ralph FSE, Irving PM, Whelan K, Lomer MCE. Nutrient intake, diet quality, and diet diversity in irritable bowel syndrome and the impact of the low FODMAP diet. J Acad Nutr Diet. 2020;120(4):535–47. doi:10.1016/j.jand.2019.01.017
  • Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux J-J, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;105(43):16731–6. doi:10.1073/pnas.0804812105
  • Dong H, Rowland I, Yaqoob P. Comparative effects of six probiotic strains on immune function in vitro. Br J Nutr. 2012;108(3):459–70. doi:10.1017/S0007114511005824
  • Shahidi F. Antioxidant factors in plant foods and selected oilseeds. Biofactors. 2000;13(1-4):179–85. doi:10.1002/biof.5520130129
  • Yakoob J, Jafri W, Mehmood MH, Abbas Z, Tariq K. Immunomodulatory effects of psyllium extract on helicobacter pylori interaction with gastric epithelial cells. J Evid Based Complementary Altern Med. 2016;21(4):NP18–24. doi:10.1177/2156587215611517
  • Nie Y, Lin Q, Luo F. Effects of non-starch polysaccharides on inflammatory bowel disease. Int J Mol Sci. 2017;18(7):1372.
  • Chan-Zapata I, Arana-Argáez VE, Torres-Romero JC, Segura-Campos MR. Anti-inflammatory effects of the protein hydrolysate and peptide fractions isolated from salvia hispanica L. seeds. Food Agric Immunol. 2019;30(1):786–803. doi:10.1080/09540105.2019.1632804
  • Martínez Leo EE, Segura Campos MR. Neuroprotective effect from salvia hispanica peptide fractions on pro-inflammatory modulation of HMC3 microglial cells. J Food Biochem. 2020;44(6):e13207. doi:10.1111/jfbc.13207
  • Currò D. Current evidence on the therapeutic use of fiber in irritable bowel syndrome. Expert Rev Gastroenterol Hepatol. 2022;16(5):425–36. doi:10.1080/17474124.2021.1924057
  • Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007;119(3):535–43. doi:10.1542/peds.2006-2447
  • El-Rashidy OF, Nassar MF, Shokair WA, El Gendy YGA. Ketogenic diet for epilepsy control and enhancement in adaptive behavior. Sci Rep. 2023;13(1):2102. doi:10.1038/s41598-023-27373-1
  • Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY. The gut microbiota mediates the anti-seizure effects of the ketogenic diet. Cell. 2018;173(7):1728–41.e1713. doi:10.1016/j.cell.2018.04.027
  • Tremont-Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. Drugs. 2000;60(5):1029–52. doi:10.2165/00003495-200060050-00005
  • Finnerup NB, Kuner R, Jensen TS. Neuropathic pain: from mechanisms to treatment. Physiol Rev. 2021;101(1):259–301. doi:10.1152/physrev.00045.2019
  • Field R, Pourkazemi F, Rooney K. Effects of a low-carbohydrate ketogenic diet on reported pain, blood biomarkers and quality of life in patients with chronic pain: a pilot randomized clinical trial. Pain Med. 2021;23(2):326–38. doi:10.1093/pm/pnab278
  • Field RJ, Field TJ, Pourkazemi F, Rooney KB. Experience of participants with chronic pain in a pilot randomized clinical trial using a ketogenic diet. Pain Manag. 2022;12(3):313–22. doi:10.2217/pmt-2021-0084
  • Sahagun E, Ward LM, Kinzig KP. Attenuation of stress-induced weight loss with a ketogenic diet. Physiol Behav. 2019;212:112654. doi:10.1016/j.physbeh.2019.112654
  • Brownlow ML, Jung SH, Moore RJ, Bechmann N, Jankord R. Nutritional ketosis affects metabolism and behavior in Sprague-Dawley rats in both control and chronic stress environments. Front Mol Neurosci. 2017;10:129. doi:10.3389/fnmol.2017.00129
  • de Toledo FW, Buchinger A, Burggrabe H, Hölz G, Kuhn C, Lischka E, et al. Fasting therapy-an expert panel update of the 2002 consensus guidelines. Complemen Med Res. 2013;20(6):434–43. doi:10.1159/000357602
  • Philpot U, Johnson MI. Diet therapy in the management of chronic pain: better diet less pain? Pain Manag. 2019;9(4):335–8. doi:10.2217/pmt-2019-0014
  • Serger E, Luengo-Gutierrez L, Chadwick JS, Kong G, Zhou L, Crawford G, et al. The gut metabolite indole-3 propionate promotes nerve regeneration and repair. Nature. 2022;607(7919):585–92. doi:10.1038/s41586-022-04884-x
  • Tofalo R, Cocchi S, Suzzi G. Polyamines and gut microbiota. Front Nutr. 2019;6:16. doi:10.3389/fnut.2019.00016
  • Williams K, Romano C, Dichter MA, Molinoff PB. Modulation of the NMDA receptor by polyamines. Life Sci. 1991;48(6):469–98. doi:10.1016/0024-3205(91)90463-L
  • Pegg AE. Functions of polyamines in mammals. J Biol Chem. 2016;291(29):14904–12. doi:10.1074/jbc.R116.731661
  • Lionetto L, Guglielmetti M, Cipolla F, Bernardini S, Koehler BE, Capi M, et al. Polyamines serum levels in episodic and chronic migraine. Expert Rev Neurother. 2021;21(2):249–54. doi:10.1080/14737175.2021.1862650
  • Estebe J-P, Degryse C, Rezzadori G, Dimache F, Daccache G, Le Naoures A, et al. Tolerance and efficacy of a polyamine-deficient diet for the treatment of perioperative pain. Nutrition. 2017;36:33–40. doi:10.1016/j.nut.2016.02.018
  • Bjørklund G, Aaseth J, Doşa MD, Pivina L, Dadar M, Pen JJ, Chirumbolo S. Does diet play a role in reducing nociception related to inflammation and chronic pain? Nutrition. 2019;66:153–65. doi:10.1016/j.nut.2019.04.007
  • Laboureyras E, Boujema MB, Mauborgne A, Simmers J, Pohl M, Simonnet G. Fentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet. Neuropsychopharmacology. 2022;47(2):599–608. doi:10.1038/s41386-021-01200-5
  • Karimi R, Mallah N, Nedjat S, Beasley MJ, Takkouche B. Association between alcohol consumption and chronic pain: a systematic review and meta-analysis. Br J Anaesth. 2022;129(3):355–65. doi:10.1016/j.bja.2022.03.010
  • Yousefi-Manesh H, Shirooie S, Noori T, Sheibani M, Tavangar SM, Hemmati S, et al. Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats. Fundam Clin Pharmacol. 2023;37(4):779–85.
  • Botschuijver S, Roeselers G, Levin E, Jonkers DM, Welting O, Heinsbroek SE, et al. Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats. Gastroenterology. 2017;153(4):1026–39. doi:10.1053/j.gastro.2017.06.004
  • Underhill DM, Braun J. Fungal microbiome in inflammatory bowel disease: a critical assessment. J Clin Invest. 2022;132:5. doi:10.1172/JCI155786
  • van Thiel I, de Jonge W, van den Wijngaard R. Fungal feelings in the irritable bowel syndrome: the intestinal mycobiome and abdominal pain. Gut Microbes. 2023;15(1):2168992. doi:10.1080/19490976.2023.2168992.
  • Gupta Y, Ernst AL, Vorobyev A, Beltsiou F, Zillikens D, Bieber K, et al. Impact of diet and host genetics on the murine intestinal mycobiome. Nat Commun. 2023;14(1):834. doi:10.1038/s41467-023-36479-z

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.