Intestinal permeability

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

The "leaky gut" syndrome or increased intestinal permeability or chronic increase of intestinal permeability hypothesis states that certain stressors increase intestinal mucosal paracellular permeability, which allows harmful bacteria and bacterial toxins to cross through the lining of intestines (gut) into circulation in the body, which is then proposed causes widespread inflammation and triggers a variety of diseases.[1][2] In a healthy digestive tract, the intestinal walls provide a tight, selective barrier to allow the absorption of nutrients but prevent the entry of bacteria or pathogens.[2]

The leaky gut hypothesis has been linked to irritable bowel syndrome (IBS), Alzheimer's disease, asthma, type 2 diabetes, numerous gastrointestinal diseases, and many others illnesses, although evidence supporting this is largely limited or lacking.[1]

Possible causes[edit | edit source]

  • Physiologic stressors proposed to cause intestinal permeability include anxiety, intense exercise and food emulsifiers.[1]
  • Short chain fatty acids can increase intestinal permeability.[2]
  • Micro-organisms in the gut increase intestinal permeability.[3]
  • Lipopolysaccharide (LPS) endotoxin from Gram-negative bacteria increases intestinal permeability.[4][5]
  • Organophosphate pesticides increase gut leakiness.[6]
  • Clostridium perfringens epsilon toxin increases small intestinal permeability in mice and rats.[7]
  • Clostridium difficile toxin A increases intestinal permeability.[8]
  • Enteropathogenic Escherichia coli bacteria disrupt the tight junction barrier function and structure.[9]
  • Many bacteria "alter tight junction state, presumably to enhance their own growth requirements. Vibrio cholerae secretes a variety of toxins and one of these, zonula occludens toxin, was recognised as increasing paracellular permeability".[10]
  • Cytomegalovirus can cause increased intestinal permeability.[11]
  • Enterovirus is associated with increased intestinal permeability.[12]
  • Mycotoxin ochratoxin A, that can contaminate cereals and animal feed, alters intestinal barrier function, and increases intestinal permeability.[13][14]
  • Mycotoxins especially trichothecenes and patulin ingested via food contamination affect the intestinal barrier integrity and can result in an increased translocation intestinal contents into the body.[15] Dr Joseph Brewer found ochratoxin A in 83% of ME/CFS patients, and trichothecenes in 44% of of ME/CFS patients.[16]
  • Blastocystis hominis a protozoan parasite can cause increased intestinal permeability.
  • TNF-alpha an inflammatory cytokine causes an increase in intestinal permeability, likely by increasing ERK1/2.[17]
  • IL-1beta causes an increase in intestinal epithelial tight junction permeability.[18]
  • Nonsteroidal antiinflammatory drug (NSAIDs) increase intestinal permeability.[19]
  • NSAIDs compromise intestinal permeability in IBS patients to a greater extent than in healthy subjects.[20]
  • Aspartame and sucralose (artificial sweeteners) increase leaky gut.[21]
  • Capsaicin from chili peppers increases leaky gut.[22]
  • Solanaceae spices (paprika, cayenne pepper) increase gut permeability.[23]
  • Chloramines (NH2Cl) in tap drinking water compromise tight junctions and so increase gut permeability.[24] Chloramines are added to drinking water along with chlorine in certain regions.
  • Gliadin (one of the components of gluten) increases gut permeability.[25][26]
  • Nonalcoholic fatty liver disease (NAFLD) is associated with increased gut permeability, and this related to the increased prevalence of SIBO in NAFLD patients.[27]
  • Traumatic brain injury (TBI) can increase intestinal permeability.[28]
  • Vitamin C in higher doses increases leaky gut.[29]
  • Compression of the vagus nerve can cause leaky gut, POTS, MCAS, anxiety, in the opinion of Dr Ross Hauser.[30]

Theory[edit | edit source]

Evidence[edit | edit source]

Prevalence[edit | edit source]

Symptom recognition[edit | edit source]

Potential treatments[edit | edit source]

Notable studies[edit | edit source]

  • 2007, Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome[32] (Full text)
  • 2007, Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syn- drome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability[33] (Full text)
  • 2013, High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients[34] (Full text)
  • 2015, Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto) immune, leaky gut, oxidative and nitrosative stress biomarkers[35] (Abstract)
  • 2015, Changes in gut and plasma microbiome following exercise challenge in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)[36] (Full text)
  • 2016, The role of microbiota and intestinal permeability in the pathophysiology of autoimmune and neuroimmune processes with an emphasis on inflammatory bowel disease type 1 diabetes and chronic fatigue syndrome[37] (Full text)
  • 2016, A role for the intestinal microbiota and virome in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)[38] (Full text)
  • 2018, The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications[39] (Full text)
  • 2018, A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)[40] (Thesis - Full text)
  • 2020, The “Leaky Gut”: Tight Junctions but Loose Associations?[1] (Full text)
  • 2020, Mitochondria and immunity in chronic fatigue syndrome[41] (Full text)
  • 2021, The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications[42] (Full text)
  • 2021, Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome[43] (Full text)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 1.3 1.4 Hollander, Daniel; Kaunitz, Jonathan D. (May 2020). "The "Leaky Gut": Tight Junctions but Loose Associations?". Digestive diseases and sciences. 65 (5): 1277–1287. doi:10.1007/s10620-019-05777-2. ISSN 0163-2116. PMC 7193723. PMID 31471860.
  2. 2.0 2.1 2.2 Usuda, Haruki; Okamoto, Takayuki; Wada, Koichiro (July 16, 2021). "Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier". International Journal of Molecular Sciences. 22 (14): 7613. doi:10.3390/ijms22147613. ISSN 1422-0067. PMC 8305009. PMID 34299233.
  3. Weaver, L T; Chapman, P D; Madeley, C R; Laker, M F; Nelson, R (1985-04). "Intestinal permeability changes and excretion of micro-organisms in stools of infants with diarrhoea and vomiting". Archives of Disease in Childhood. 60 (4): 326–332. ISSN 0003-9888. PMC 1777215. PMID 3923945. Check date values in: |date= (help)
  4. O'Dwyer, S. T.; Michie, H. R.; Ziegler, T. R.; Revhaug, A.; Smith, R. J.; Wilmore, D. W. (1988-12). "A single dose of endotoxin increases intestinal permeability in healthy humans". Archives of Surgery (Chicago, Ill.: 1960). 123 (12): 1459–1464. doi:10.1001/archsurg.1988.01400360029003. ISSN 0004-0010. PMID 3142442. Check date values in: |date= (help)
  5. Guo, Shuhong; Al-Sadi, Rana; Said, Hamid M.; Ma, Thomas Y. (2013-02). "Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14". The American Journal of Pathology. 182 (2): 375–387. doi:10.1016/j.ajpath.2012.10.014. ISSN 1525-2191. PMC 3562736. PMID 23201091. Check date values in: |date= (help)
  6. Liang, Yiran; Zhan, Jing; Liu, Donghui; Luo, Mai; Han, Jiajun; Liu, Xueke; Liu, Chang; Cheng, Zheng; Zhou, Zhiqiang; Wang, Peng (February 11, 2019). "Organophosphorus pesticide chlorpyrifos intake promotes obesity and insulin resistance through impacting gut and gut microbiota". Microbiome. 7 (1): 19. doi:10.1186/s40168-019-0635-4. ISSN 2049-2618. PMC 6371608. PMID 30744700.
  7. Goldstein, Jorge; Morris, Winston E.; Loidl, César Fabián; Tironi-Farinati, Carla; McClane, Bruce A.; Uzal, Francisco A.; Fernandez Miyakawa, Mariano E. (September 18, 2009). "Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats". PloS One. 4 (9): e7065. doi:10.1371/journal.pone.0007065. ISSN 1932-6203. PMC 2739291. PMID 19763257.
  8. Moore, R.; Pothoulakis, C.; LaMont, J. T.; Carlson, S.; Madara, J. L. (1990-08). "C. difficile toxin A increases intestinal permeability and induces Cl- secretion". The American Journal of Physiology. 259 (2 Pt 1): G165–172. doi:10.1152/ajpgi.1990.259.2.G165. ISSN 0002-9513. PMID 2116728. Check date values in: |date= (help)
  9. Shifflett, Donnie E.; Clayburgh, Daniel R.; Koutsouris, Athanasia; Turner, Jerrold R.; Hecht, Gail A. (2005-10). "Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo". Laboratory Investigation; a Journal of Technical Methods and Pathology. 85 (10): 1308–1324. doi:10.1038/labinvest.3700330. ISSN 0023-6837. PMID 16127426. Check date values in: |date= (help)
  10. Arrieta, M C; Bistritz, L; Meddings, J B (2006-10). "Alterations in intestinal permeability". Gut. 55 (10): 1512–1520. doi:10.1136/gut.2005.085373. ISSN 0017-5749. PMC 1856434. PMID 16966705. Check date values in: |date= (help)
  11. de Maar, E. F.; Kleibeuker, J. H.; Boersma-van Ek, W.; The, T. H.; van Son, W. J. (1996). "Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients". Transplant International: Official Journal of the European Society for Organ Transplantation. 9 (6): 576–580. doi:10.1007/BF00335558. ISSN 0934-0874. PMID 8914238.
  12. Vorobjova, Tamara; Raikkerus, Helerin; Kadaja, Lumme; Talja, Ija; Uibo, Oivi; Heilman, Kaire; Uibo, Raivo (2017-02). "Circulating Zonulin Correlates with Density of Enteroviruses and Tolerogenic Dendritic Cells in the Small Bowel Mucosa of Celiac Disease Patients". Digestive Diseases and Sciences. 62 (2): 358–371. doi:10.1007/s10620-016-4403-z. ISSN 1573-2568. PMID 27995404. Check date values in: |date= (help)
  13. Maresca, M.; Mahfoud, R.; Pfohl-Leszkowicz, A.; Fantini, J. (October 1, 2001). "The mycotoxin ochratoxin A alters intestinal barrier and absorption functions but has no effect on chloride secretion". Toxicology and Applied Pharmacology. 176 (1): 54–63. doi:10.1006/taap.2001.9254. ISSN 0041-008X. PMID 11578148.
  14. McLaughlin, John; Padfield, Philip J.; Burt, Julian P. H.; O'Neill, Catherine A. (2004-11). "Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms". American Journal of Physiology. Cell Physiology. 287 (5): C1412–1417. doi:10.1152/ajpcell.00007.2004. ISSN 0363-6143. PMID 15229101. Check date values in: |date= (help)
  15. Akbari, Peyman; Braber, Saskia; Varasteh, Soheil; Alizadeh, Arash; Garssen, Johan; Fink-Gremmels, Johanna (2017-03). "The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins". Archives of Toxicology. 91 (3): 1007–1029. doi:10.1007/s00204-016-1794-8. ISSN 1432-0738. PMC 5316402. PMID 27417439. Check date values in: |date= (help)
  16. Brewer, Joseph H.; Thrasher, Jack D.; Straus, David C.; Madison, Roberta A.; Hooper, Dennis (April 11, 2013). "Detection of mycotoxins in patients with chronic fatigue syndrome". Toxins. 5 (4): 605–617. doi:10.3390/toxins5040605. ISSN 2072-6651. PMC 3705282. PMID 23580077.
  17. Al-Sadi, Rana; Guo, Shuhong; Ye, Dongmei; Ma, Thomas Y. (2013-12). "TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1". The American Journal of Pathology. 183 (6): 1871–1884. doi:10.1016/j.ajpath.2013.09.001. ISSN 1525-2191. PMC 5745548. PMID 24121020. Check date values in: |date= (help)
  18. Al-Sadi, Rana M.; Ma, Thomas Y. (April 1, 2007). "IL-1beta causes an increase in intestinal epithelial tight junction permeability". Journal of Immunology (Baltimore, Md.: 1950). 178 (7): 4641–4649. doi:10.4049/jimmunol.178.7.4641. ISSN 0022-1767. PMC 3724221. PMID 17372023.
  19. Bjarnason, Ingvar; Takeuchi, Ken (2009). "Intestinal permeability in the pathogenesis of NSAID-induced enteropathy". Journal of Gastroenterology. 44 Suppl 19: 23–29. doi:10.1007/s00535-008-2266-6. ISSN 0944-1174. PMID 19148789.
  20. Kerckhoffs, Angèle P. M.; Akkermans, Louis M. A.; de Smet, Martin B. M.; Besselink, Marc G. H.; Hietbrink, Falco; Bartelink, Imke H.; Busschers, Wim B.; Samsom, Melvin; Renooij, Willem (2010-03). "Intestinal permeability in irritable bowel syndrome patients: effects of NSAIDs". Digestive Diseases and Sciences. 55 (3): 716–723. doi:10.1007/s10620-009-0765-9. ISSN 1573-2568. PMID 19255843. Check date values in: |date= (help)
  21. Shil, Aparna; Olusanya, Oluwatobi; Ghufoor, Zaynub; Forson, Benjamin; Marks, Joanne; Chichger, Havovi (June 22, 2020). "Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3". Nutrients. 12 (6): 1862. doi:10.3390/nu12061862. ISSN 2072-6643. PMC 7353258. PMID 32580504.
  22. Shiobara, Tomoko; Usui, Takeo; Han, Junkyu; Isoda, Hiroko; Nagumo, Yoko (2013). "The reversible increase in tight junction permeability induced by capsaicin is mediated via cofilin-actin cytoskeletal dynamics and decreased level of occludin". PloS One. 8 (11): e79954. doi:10.1371/journal.pone.0079954. ISSN 1932-6203. PMC 3832373. PMID 24260326.
  23. Jensen-Jarolim, E.; Gajdzik, L.; Haberl, I.; Kraft, D.; Scheiner, O.; Graf, J. (1998-03). "Hot spices influence permeability of human intestinal epithelial monolayers". The Journal of Nutrition. 128 (3): 577–581. doi:10.1093/jn/128.3.577. ISSN 0022-3166. PMID 9482766. Check date values in: |date= (help)
  24. Musch, Mark W.; Walsh-Reitz, Margaret Mary; Chang, Eugene B. (2006-02). "Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption". American Journal of Physiology. Gastrointestinal and Liver Physiology. 290 (2): G222–231. doi:10.1152/ajpgi.00301.2005. ISSN 0193-1857. PMID 16239402. Check date values in: |date= (help)
  25. Drago, Sandro; El Asmar, Ramzi; Di Pierro, Mariarosaria; Grazia Clemente, Maria; Tripathi, Amit; Sapone, Anna; Thakar, Manjusha; Iacono, Giuseppe; Carroccio, Antonio; D'Agate, Cinzia; Not, Tarcisio (2006-04). "Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines". Scandinavian Journal of Gastroenterology. 41 (4): 408–419. doi:10.1080/00365520500235334. ISSN 0036-5521. PMID 16635908. Check date values in: |date= (help)
  26. Lammers, Karen M.; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir; Alkan, Sefik; Netzel-Arnett, Sarah (2008-07). "Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3". Gastroenterology. 135 (1): 194–204.e3. doi:10.1053/j.gastro.2008.03.023. ISSN 1528-0012. PMC 2653457. PMID 18485912. Check date values in: |date= (help)
  27. Miele, Luca; Valenza, Venanzio; La Torre, Giuseppe; Montalto, Massimo; Cammarota, Giovanni; Ricci, Riccardo; Mascianà, Roberta; Forgione, Alessandra; Gabrieli, Maria L.; Perotti, Germano; Vecchio, Fabio M. (2009-06). "Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease". Hepatology (Baltimore, Md.). 49 (6): 1877–1887. doi:10.1002/hep.22848. ISSN 1527-3350. PMID 19291785. Check date values in: |date= (help)
  28. Bansal, Vishal; Costantini, Todd; Kroll, Lauren; Peterson, Carrie; Loomis, William; Eliceiri, Brian; Baird, Andrew; Wolf, Paul; Coimbra, Raul (2009-08). "Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis". Journal of Neurotrauma. 26 (8): 1353–1359. doi:10.1089/neu.2008.0858. ISSN 1557-9042. PMC 2989839. PMID 19344293. Check date values in: |date= (help)
  29. Sequeira, Ivana R.; Kruger, Marlena C.; Hurst, Roger D.; Lentle, Roger G. (2015-09). "Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability". Basic & Clinical Pharmacology & Toxicology. 117 (3): 195–203. doi:10.1111/bcpt.12388. ISSN 1742-7843. PMID 25641731. Check date values in: |date= (help)
  30. Hauser, Ross. "Compression of the vagus nerve due to cervical instability in Ehlers-Danlos Syndrome". www.youtube.com. Timecode 2:24. Retrieved June 2, 2024.
  31. Rapin, Jean Robert; Wiernsperger, Nicolas (2010-6). "Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine". Clinics. 65 (6): 635–643. doi:10.1590/S1807-59322010000600012. ISSN 1807-5932. PMC 2898551. PMID 20613941. Check date values in: |date= (help)
  32. Maes, Michael; Coucke, Francis; Leunis, Jean-Claude (December 2007). "Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome". Neuro Endocrinology Letters. 28 (6): 739–744. ISSN 0172-780X. PMID 18063928.
  33. Maes, Michael; Mihaylova, Ivana; Leunis, Jean-Claude (April 1, 2007). "Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability". Journal of Affective Disorders. 99 (1): 237–240. doi:10.1016/j.jad.2006.08.021. ISSN 0165-0327.
  34. Frémont, Marc; Coomans, Danny; Massart, Sebastien; De Meirleir, Kenny (August 1, 2013). "High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients". Anaerobe. 22: 50–56. doi:10.1016/j.anaerobe.2013.06.002. ISSN 1075-9964.
  35. Maes, Michael; Bosmans, Eugene; Kubera, Marta (2015). "Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers". Neuro Endocrinology Letters. 36 (5): 439–446. ISSN 0172-780X. PMID 26707044.
  36. Shukla, Sanjay K.; Cook, Dane; Meyer, Jacob; Vernon, Suzanne D.; Le, Thao; Clevidence, Derek; Robertson, Charles E.; Schrodi, Steven J.; Yale, Steven; Frank, Daniel N. (December 18, 2015). "Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". PLOS ONE. 10 (12): e0145453. doi:10.1371/journal.pone.0145453. ISSN 1932-6203. PMC 4684203. PMID 26683192.
  37. Morris, Gerwyn; Berk, Michael; Carvalho, André F.; Caso, Javier R.; Sanz, Yolanda; Maes, Michael (2016). "The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome". Current Pharmaceutical Design. 22 (40): 6058–6075. doi:10.2174/1381612822666160914182822. ISSN 1873-4286. PMID 27634186.
  38. Morris, Gerwyn; Berk, Michael; Carvalho, André F.; Caso, Javier R.; Sanz, Yolanda; Maes, Michael (2016). "The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome". Current Pharmaceutical Design. 22 (40): 6058–6075. doi:10.2174/1381612822666160914182822. ISSN 1873-4286. PMID 27634186.
  39. Varesi, Angelica; Deumer, Undine-Sophie; Ananth, Sanjana; Ricevuti, Giovanni (October 29, 2021). "The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications". Journal of Clinical Medicine. 10 (21): 5077. doi:10.3390/jcm10215077. ISSN 2077-0383. PMC 8584653. PMID 34768601.
  40. Vipond, Daniel (2018). "A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)". University of East Anglia.
  41. Anderson, G.; Maes, M. (December 20, 2020). "Mitochondria and immunity in chronic fatigue syndrome". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 103: 109976. doi:10.1016/j.pnpbp.2020.109976. ISSN 0278-5846.
  42. Varesi, Angelica; Deumer, Undine-Sophie; Ananth, Sanjana; Ricevuti, Giovanni (October 29, 2021). "The Emerging Role of Gut Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Current Evidence and Potential Therapeutic Applications". Journal of Clinical Medicine. 10 (21): 5077. doi:10.3390/jcm10215077. ISSN 2077-0383. PMC 8584653. PMID 34768601.
  43. Simonato, Manuela; Dall’Acqua, Stefano; Zilli, Caterina; Sut, Stefania; Tenconi, Romano; Gallo, Nicoletta; Sfriso, Paolo; Sartori, Leonardo; Cavallin, Francesco; Fiocco, Ugo; Cogo, Paola (November 19, 2021). "Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Biomedicines. 9 (11): 1724. doi:10.3390/biomedicines9111724. ISSN 2227-9059. PMC 8615774. PMID 34829952.