title: Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.
abstract: OBJECTIVE
  To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.
  
  
  METHODS
  Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study.
  
  
  METHODS
  HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.
  
  
  RESULTS
  All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046).
  
  
  CONCLUSIONS
  SBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.
authors: aUniversity of California Davis Medical School bVeterans Administration Northern California Healthcare System, Sacramento cUniversity of California - Davis dCenter for Comparative Medicine, Davis, California eVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland fBaylor College of Medicine and Texas Children's Hospital, Houston, Texas gCARES Clinic, Sacramento, California hMayo Clinic, Rochester, Minnesota, USA.
authors: David M
authors: DM
authors: Asmuth
authors: Zhong-Min
authors: ZM
authors: Ma
authors: Anthony
authors: A
authors: Albanese
authors: Netanya G
authors: NG
authors: Sandler
authors: Sridevi
authors: S
authors: Devaraj
authors: Thomas H
authors: TH
authors: Knight
authors: Neil M
authors: NM
authors: Flynn
authors: Tammy
authors: T
authors: Yotter
authors: Juan-Carlos
authors: JC
authors: Garcia
authors: Emily
authors: E
authors: Tsuchida
authors: Tsung-Teh
authors: TT
authors: Wu
authors: Daniel C
authors: DC
authors: Douek
authors: Christopher J
authors: CJ
authors: Miller
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D002417:Cattle; D004032:Diet / Q000379:methods*; D004386:Duodenum / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019053:HIV Enteropathy / Q000276:immunology / Q000628:therapy*; D006801:Humans; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000302:isolation & purification; D008297:Male; D010865:Pilot Projects; D012712:Serum Globulins / Q000008:administration & dosage* / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D007136:Immunoglobulins; D012712:Serum Globulins
references: AIDS. 1996 Oct;10(12):1385-91
references: 8902068
references: J Infect Dis. 2011 Mar 15;203(6):780-90
references: 21252259
references: J Infect Dis. 2008 Aug 15;198(4):456-64
references: 18598193
references: J Clin Invest. 2011 Mar;121(3):998-1008
references: 21393864
references: J Nutr. 2006 Nov;136(11):2838-43
references: 17056810
references: Aliment Pharmacol Ther. 2013 Feb;37(4):482-90
references: 23289539
references: J Nutr. 2010 Jan;140(1):25-30
references: 19923397
references: PLoS Med. 2006 Dec;3(12):e484
references: 17147468
references: Blood. 2007 Feb 1;109(3):1174-81
references: 17047153
references: Prog Lipid Res. 1996 Sep;35(3):243-82
references: 9082452
references: Nat Med. 2006 Dec;12(12):1365-71
references: 17115046
references: J Immunol Methods. 2003 Aug;279(1-2):17-31
references: 12969544
references: Viral Immunol. 2004;17(1):109-13
references: 15018667
references: Ann Intern Med. 1985 May;102(5):619-22
references: 3985513
references: Int J Mol Med. 2009 Aug;24(2):143-52
references: 19578787
references: Best Pract Res Clin Gastroenterol. 2003 Jun;17(3):397-425
references: 12763504
references: AIDS. 2010 Aug 24;24(13):2029-39
references: 20588162
references: Mucosal Immunol. 2008 Nov;1(6):497-507
references: 19079217
references: Infect Immun. 1994 Jul;62(7):2874-84
references: 7911786
references: J Pathol. 2008 Jan;214(2):199-210
references: 18161745
references: N Engl J Med. 1994 Nov 10;331(19):1286-92
references: 7935686
references: Gastroenterology. 1995 May;108(5):1566-81
references: 7729650
references: J Infect Dis. 2009 Apr 15;199(8):1177-85
references: 19265479
references: J Anim Sci. 2009 Apr;87(14 Suppl):E92-100
references: 18820151
references: J Nutr. 2004 Oct;134(10):2667-72
references: 15465764
references: Gut. 1995 Nov;37(5):623-9
references: 8549936
references: J Nutr Biochem. 2007 Dec;18(12):778-84
references: 17475463
references: AIDS. 1994 Feb;8(2):205-11
references: 7913816
references: Baillieres Clin Gastroenterol. 1990 Jun;4(2):361-73
references: 2282381
references: J Infect Dis. 2007 Feb 15;195(4):551-61
references: 17230415
references: Ann Intern Med. 1984 Oct;101(4):421-8
references: 6476631
references: Clin Vaccine Immunol. 2006 May;13(5):556-60
references: 16682476
references: J Acquir Immune Defic Syndr. 2011 Aug 15;57(5):363-70
references: 21436711
references: J Virol. 2003 Nov;77(21):11708-17
references: 14557656
references: J Leukoc Biol. 1997 Jul;62(1):30-3
references: 9225989
references: Infect Immun. 1994 May;62(5):2132-4
references: 8168984
references: J Anim Sci. 2006 Oct;84(10):2735-42
references: 16971575
references: J Clin Invest. 2002 Oct;110(8):1133-9
references: 12393849
references: J Infect Dis. 2011 Mar 15;203(6):810-3
references: 21343147
references: J Virol. 2007 Jan;81(2):599-612
references: 17065209
references: AIDS. 2012 Jan 14;26(2):139-48
references: 22045342
references: J Anim Sci. 2005 Dec;83(12):2876-85
references: 16282627
references: Proc Nutr Soc. 2010 Aug;69(3):447-53
references: 20576204
references: Nat Med. 2005 May;11(5):469-70
references: 15875046
references: AIDS. 2005 Dec 2;19(18):2169-71
references: 16284469
references: J Nutr. 2008 Mar;138(3):533-7
references: 18287362
references: Gut. 1999 Jul;45(1):70-6
references: 10369707
references: Epidemiology. 1990 Jan;1(1):43-6
references: 2081237
references: Eur J Clin Nutr. 2008 Jan;62(1):39-50
references: 17299460
references: J Nutr. 2000 Jan;130(1):21-6
references: 10613760
references: J Nutr. 2011 Jul;141(7):1312-7
references: 21613450
references: AIDS. 2012 Aug 24;26(13):1625-34
references: 22820612
references: Science. 1998 Apr 17;280(5362):427-31
references: 9545219
references: J Clin Gastroenterol. 2007 May-Jun;41(5):484-90
references: 17450031
references: Clin Infect Dis. 2012 Sep;55(6):860-7
references: 22700829
references: Histopathology. 1990 Feb;16(2):133-40
references: 2323734
references: Am J Clin Nutr. 2005 Apr;81(4):792-8
references: 15817854
references: J Acquir Immune Defic Syndr. 2006 Sep;43(1):27-34
references: 16878047
references: J Dairy Sci. 2007 Dec;90(12):5726-31
references: 18024765
references: Nature. 2005 Apr 28;434(7037):1148-52
references: 15793562
references: Clin Liver Dis. 2008 Nov;12(4):915-37, xi
references: 18984474
references: J Exp Med. 2004 Sep 20;200(6):761-70
references: 15365095