PHT Live – Autoimmune Disorders

This weeks hangout discussed novel natural treatments for autoimmune disease.  Many facets to this were discussed including the foods that we eat, infections, stress, hormones, and toxic exposure.  The articles below focus on the growing knowledge regarding infectious triggers of autoimmune disease, and how the mouth and the gastrointestinal tract are key areas of this research.

Several of the articles we have posted concern mouth and gastrointestinal bacteria that are being found to have implications in Rheumatoid Arthritis.  Not only is the DNA of these bacteria being found in the joints of RA patient’s, but it is also being observed that the biochemical reaction that leads to RA, termed citrullination, is caused by one and possibly both of these bacteria.
Other articles attached discuss the relationship between the gastrointestinal barrier and autoimmune disease.  In essence, from a simplistic standpoint, we want the cells of our gastrointestinal tract to be bound together tightly, analogous to a dam.  The current literature is demonstrating that in certain patient populations the immune system can target the proteins that bind the cells of our gastrointestinal tract together, and therefore compromise this barrier between the bacteria in our gut and our immune system.
For further reading, I highly recommend reading the articles by Alessia Fasano, MD on the pubmed database as well as Integrative Rheumatology by Dr. Alex Vasquez, D.C., N.D., D.O.

Below are the referenced articles

1.The link between periodontal disease and rheumatoid arthritis: an updated review.
Koziel J, Mydel P, Potempa J.
Curr Rheumatol Rep. 2014 Mar;16(3):408. doi: 10.1007/s11926-014-0408-9.
PMID: 24458478 [PubMed – in process] Free PMC Article
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2.Bugs & us: the role of the gut in autoimmunity.
Luckey D, Gomez A, Murray J, White B, Taneja V.
Indian J Med Res. 2013 Nov;138(5):732-43.
PMID: 24434325 [PubMed – in process] Free PMC Article
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3.Role of SFB in autoimmune arthritis: An example of regulation of autoreactive T cell sensitivity in the gut.
Chappert P.
Gut Microbes. 2014 Feb 6;5(2). [Epub ahead of print]
PMID: 24637598 [PubMed – as supplied by publisher]
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4.Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association.
Atanasova KR, Yilmaz O.
Mol Oral Microbiol. 2014 Apr;29(2):55-66. doi: 10.1111/omi.12047. Epub 2014 Feb 8.
PMID: 24506890 [PubMed – in process]
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5.Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry.
Alam J, Kim YC, Choi Y.
Immune Netw. 2014 Feb;14(1):7-13. Epub 2014 Feb 21. Review.
PMID: 24605075 [PubMed – as supplied by publisher] Free PMC Article
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6.Treatment of rheumatoid arthritis with ornidazole: a randomized, double-blind, placebo-controlled study.
Ogrendik M.
Rheumatol Int. 2006 Oct;26(12):1132-7. Epub 2006 Jun 13.
PMID: 16770616 [PubMed – indexed for MEDLINE]
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7.Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients.
Moen K, Brun JG, Madland TM, Tynning T, Jonsson R.
Clin Diagn Lab Immunol. 2003 Nov;10(6):1043-50.
PMID: 14607865 [PubMed – indexed for MEDLINE] Free PMC Article
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8.Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs.
Moen K, Brun JG, Valen M, Skartveit L, Eribe EK, Olsen I, Jonsson R.
Clin Exp Rheumatol. 2006 Nov-Dec;24(6):656-63.
PMID: 17207381 [PubMed – indexed for MEDLINE]
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9.Fecal microbiota in early rheumatoid arthritis.
Vaahtovuo J, Munukka E, Korkeamäki M, Luukkainen R, Toivanen P.
J Rheumatol. 2008 Aug;35(8):1500-5. Epub 2008 Jun 1.
PMID: 18528968 [PubMed – indexed for MEDLINE]
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10.Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients.
Martinez-Martinez RE, Abud-Mendoza C, Patiño-Marin N, Rizo-Rodríguez JC, Little JW, Loyola-Rodríguez JP.
J Clin Periodontol. 2009 Dec;36(12):1004-10. doi: 10.1111/j.1600-051X.2009.01496.x.
PMID: 19929953 [PubMed – indexed for MEDLINE]
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11.Does periodontopathic bacterial infection contribute to the etiopathogenesis of the autoimmune disease rheumatoid arthritis?
Ogrendik M.
Discov Med. 2012 May;13(72):349-55.
PMID: 22642916 [PubMed – indexed for MEDLINE] Free Article
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12.Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis.
Scher JU, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A, Lipuma L, Attur M, Pillinger MH, Weissmann G, Littman DR, Pamer EG, Bretz WA, Abramson SB.
Arthritis Rheum. 2012 Oct;64(10):3083-94. doi: 10.1002/art.34539.
PMID: 22576262 [PubMed – indexed for MEDLINE] Free PMC Article
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13.Effects of clarithromycin in patients with active rheumatoid arthritis.
Ogrendik M.
Curr Med Res Opin. 2007 Mar;23(3):515-22.
PMID: 17355733 [PubMed – indexed for MEDLINE]
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14.Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens.
Ogrendik M.
Int J Gen Med. 2013 May 24;6:383-6. doi: 10.2147/IJGM.S45929. Print 2013.
PMID: 23737674 [PubMed] Free PMC Article
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15.Rheumatoid arthritis: Prevotella copri associated with new-onset untreated RA.
Bernard NJ.
Nat Rev Rheumatol. 2014 Jan;10(1):2. doi: 10.1038/nrrheum.2013.187. Epub 2013 Nov 26. No abstract available.
PMID: 24275964 [PubMed – in process]
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16.Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis.
Miquel E, Cassina A, Martínez-Palma L, Souza JM, Bolatto C, Rodríguez-Bottero S, Logan A, Smith RA, Murphy MP, Barbeito L, Radi R, Cassina P.
Free Radic Biol Med. 2014 Feb 26;70C:204-213. doi: 10.1016/j.freeradbiomed.2014.02.019. [Epub ahead of print]
PMID: 24582549 [PubMed – as supplied by publisher]
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17.Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice.
Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong Z, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV.
Proc Natl Acad Sci U S A. 2014 Mar 3. [Epub ahead of print]
PMID: 24591593 [PubMed – as supplied by publisher] Free Article
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18.Autophagy and apoptosis dysfunction in neurodegenerative disorders.
Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, ?os MJ.
Prog Neurobiol. 2014 Jan;112:24-49. doi: 10.1016/j.pneurobio.2013.10.004. Epub 2013 Nov 6.
PMID: 24211851 [PubMed – in process]
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19.Neuropsychiatric changes precede classic motor symptoms in ALS and do not affect survival.
Mioshi E, Caga J, Lillo P, Hsieh S, Ramsey E, Devenney E, Hornberger M, Hodges JR, Kiernan MC.
Neurology. 2014 Jan 14;82(2):149-55. doi: 10.1212/WNL.0000000000000023. Epub 2013 Dec 11.
PMID: 24336140 [PubMed – indexed for MEDLINE]
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20.Basal ganglia involvement in amyotrophic lateral sclerosis.
Bede P, Elamin M, Byrne S, McLaughlin RL, Kenna K, Vajda A, Pender N, Bradley DG, Hardiman O.
Neurology. 2013 Dec 10;81(24):2107-15. doi: 10.1212/01.wnl.0000437313.80913.2c. Epub 2013 Nov 8.
PMID: 24212388 [PubMed – indexed for MEDLINE]
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21.Microglia and motor neurons during disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis: changes in arginase1 and inducible nitric oxide synthase.
Lewis KE, Rasmussen AL, Bennett W, King A, West AK, Chung RS, Chuah MI.
J Neuroinflammation. 2014 Mar 23;11(1):55. [Epub ahead of print]
PMID: 24655927 [PubMed – as supplied by publisher] Free Article
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22.Berberine inhibits cytosolic phospholipase A2 and protects against LPS-induced lung injury and lethality independent of the alpha2-adrenergic receptor in mice.
Zhang HQ, Wang HD, Lu DX, Qi RB, Wang YP, Yan YX, Fu YM.
Shock. 2008 May;29(5):617-22. doi: 10.1097/SHK.0b013e318157ea14.
PMID: 18414236 [PubMed – indexed for MEDLINE]
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23.Global transcriptional profiles of Staphylococcus aureus treated with berberine chloride.
Wang D, Yu L, Xiang H, Fan J, He L, Guo N, Feng H, Deng X.
FEMS Microbiol Lett. 2008 Feb;279(2):217-25. doi: 10.1111/j.1574-6968.2007.01031.x. Epub 2008 Jan 3.
PMID: 18179590 [PubMed – indexed for MEDLINE]
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24.Preparation and evaluation of a microemulsion for oral delivery of berberine.
Gui SY, Wu L, Peng DY, Liu QY, Yin BP, Shen JZ.
Pharmazie. 2008 Jul;63(7):516-9.
PMID: 18717486 [PubMed – indexed for MEDLINE]
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25.Effect of berberine on Staphylococcus epidermidis biofilm formation.
Wang X, Yao X, Zhu Z, Tang T, Dai K, Sadovskaya I, Flahaut S, Jabbouri S.
Int J Antimicrob Agents. 2009 Jul;34(1):60-6. doi: 10.1016/j.ijantimicag.2008.10.033. Epub 2009 Jan 20.
PMID: 19157797 [PubMed – indexed for MEDLINE]
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26.Berberine chloride causes a caspase-independent, apoptotic-like death in Leishmania donovani promastigotes.
Saha P, Sen R, Hariharan C, Kumar D, Das P, Chatterjee M.
Free Radic Res. 2009;43(11):1101-10. doi: 10.1080/10715760903186124.
PMID: 19669998 [PubMed – indexed for MEDLINE]
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27.In vitro antifungal activity of the berberine and its synergism with fluconazole.
Iwazaki RS, Endo EH, Ueda-Nakamura T, Nakamura CV, Garcia LB, Filho BP.
Antonie Van Leeuwenhoek. 2010 Feb;97(2):201-5. doi: 10.1007/s10482-009-9394-8. Epub 2009 Nov 2.
PMID: 19882381 [PubMed – indexed for MEDLINE]
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28.Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders.
Kulkarni SK, Dhir A.
Phytother Res. 2010 Mar;24(3):317-24. doi: 10.1002/ptr.2968. Review.
PMID: 19998323 [PubMed – indexed for MEDLINE]
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29.Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells.
Li N, Gu L, Qu L, Gong J, Li Q, Zhu W, Li J.
Eur J Pharm Sci. 2010 Apr 16;40(1):1-8. doi: 10.1016/j.ejps.2010.02.001. Epub 2010 Feb 10.
PMID: 20149867 [PubMed – indexed for MEDLINE]
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30.Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine.
Lv XY, Li J, Zhang M, Wang CM, Fan Z, Wang CY, Chen L.
AAPS PharmSciTech. 2010 Mar;11(1):372-82. doi: 10.1208/s12249-010-9386-z. Epub 2010 Mar 17.
PMID: 20237966 [PubMed – indexed for MEDLINE] Free PMC Article
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31.Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San.
Chin LW, Cheng YW, Lin SS, Lai YY, Lin LY, Chou MY, Chou MC, Yang CC.
Arch Virol. 2010 Dec;155(12):1933-41. doi: 10.1007/s00705-010-0779-9. Epub 2010 Aug 5.
PMID: 20686799 [PubMed – indexed for MEDLINE]
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32.Antidiarrheal activity, chemical and toxicity profile of Berberis aristata.
Joshi PV, Shirkhedkar AA, Prakash K, Maheshwari VL.
Pharm Biol. 2011 Jan;49(1):94-100. doi: 10.3109/13880209.2010.500295. Epub 2010 Aug 25.
PMID: 20738174 [PubMed – indexed for MEDLINE]
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33.Human intestinal microbiota and type 1 diabetes.
Vaarala O.
Curr Diab Rep. 2013 Oct;13(5):601-7. doi: 10.1007/s11892-013-0409-5. Review.
PMID: 23934614 [PubMed – indexed for MEDLINE]
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34.Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.
Fasano A.
Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008. Review.
PMID: 21248165 [PubMed – indexed for MEDLINE] Free Article
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35.Leaking gut in type 1 diabetes.
Vaarala O.
Curr Opin Gastroenterol. 2008 Nov;24(6):701-6. doi: 10.1097/MOG.0b013e32830e6d98. Review.
PMID: 19122519 [PubMed – indexed for MEDLINE]
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36.Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases.
Fasano A, Shea-Donohue T.
Nat Clin Pract Gastroenterol Hepatol. 2005 Sep;2(9):416-22. Review.
PMID: 16265432 [PubMed – indexed for MEDLINE]
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37.Is the origin of type 1 diabetes in the gut?
Vaarala O.
Immunol Cell Biol. 2012 Mar;90(3):271-6. doi: 10.1038/icb.2011.115. Epub 2012 Jan 31. Review.
PMID: 22290506 [PubMed – indexed for MEDLINE]
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38.Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall.
Fasano A.
Am J Pathol. 2008 Nov;173(5):1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2.
PMID: 18832585 [PubMed – indexed for MEDLINE] Free PMC Article
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39.Increased intestinal permeability precedes clinical onset of type 1 diabetes.
Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, Piemonti L, Pastore MR, Paroni R.
Diabetologia. 2006 Dec;49(12):2824-7. Epub 2006 Oct 7.
PMID: 17028899 [PubMed – indexed for MEDLINE]
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