HIV attacks the gastrointestinal tract.
It really shocked when I read what influence HIV has on the gastrointestinal tract of humans. When not treated, this leads from diarrhea to pancreatic dysfunction and as a consequence to malabsorption and weight loss which in the end make it much riskier to die from a normal infection because the body has no more means to fight it off.
What really gives me hope is that HAART (highly active anti-retroviral therapy) normalizes everything. All the HIV patients who have extreme gastrointestinal problems (including increased intestinal permeability) improve on treatment till the gastrointestinal tract normalizes completely (!). I cannot say for sure of course but to me it looks much like we suffer from a viral disease! So if XMRV or other viruses are the cause of CFS this would perfectly fit into the picture since many of us have gastrointestinal problems.
Prof De Meirleir is using a test called "Immunobilan" which checks for IgAs and IgMs directed at intestinal bacteria. Positive results indicate a translocation of bacteria. The following study shows that this is also a problem with HIV:
Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation.
Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals.
PMID: 20386714
Here are some more conclusions:
CONCLUSIONS: Suppressive HAART abrogates HIV-induced intestinal barrier defect and villous atrophy. The HIV-induced barrier defect is due to altered tight junction protein composition and elevated epithelial apoptoses. Mucosal cytokines are mediators of the HIV-induced mucosal barrier defect and villous atrophy.
PMID: 18936106
The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20-70% of children.
PMID: 15612836
CONCLUSIONS: Cell-cell interaction of HIV-infected macrophages with PBMC leads to a release of cytokines sufficient to alter intestinal epithelial barrier function. The main effect was mediated by TNFalpha inducing a leak-flux which may contribute to the diarrhoea by HIV per se (HIV-enteropathy).
PMID: 11953464
CONCLUSION: Because systemic exposure of oral ganciclovir (Valcyte) is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.
PMID: 11015151
BACKGROUND: Impaired intestinal function could account for diarrhoea and weight loss, which are common features of advanced human immunodeficiency virus (HIV) infection.
CONCLUSIONS: These findings suggest a loss of intestinal functional absorptive surface as HIV disease progresses. This process may be present at the early stage of infection. Impaired intestinal permeability is observed later in AIDS patients when digestive signs are present, particularly diarrhoea.
PMID: 10048729
Weight loss, the gut and the inflammatory response in aids patients.
Stein TP, Koerner B, Schluter MD, Leskiw MJ, Gaprindachvilli T, Richards EW, Cope FO, Condolucci D.
Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
Abstract
The objective of this study was to test the hypothesis that the integrity of the large bowel wall in AIDS patients is compromised in a manner that favours the chronic translocation of bacteria and/or products of bacterial metabolism into the bloodstream. When such translocation occurs, it induces a characteristic stress/inflammatory response in the body. Urinary butyrate, a unique product of colonic microbial metabolism, was used to assess gut wall permeability. Excretion of the pro-inflammatory cytokine IL-6 in the urine was used as a marker for the stress/inflammatory response. Four groups of subjects were studied, controls (n = 12), HIV + (n = 35) and AIDS patients with (n = 14) and without (n = 17) weight loss. Results: measurable amounts of interleukin 6 (IL-6) and butyrate were found in the urine of all subjects. There were no significant differences in IL-6 excretion between the controls (0.68 +/- 0.64 pg/ml), asymptomatic HIV + subjects (0.59 +/- 0.37 pg/ml) and AIDS patients without weight loss (1.18 +/- 0.33 pg/ml) but IL-6 levels were significantly higher in the AIDS group with weight loss (4.02 +/- 1.26 pg/ml, P < 0.05). A similar pattern of results was found with interleukin 1 receptor antagonist (IL-1ra). Like IL-6 and (IL-1ra), urinary butyrate levels were increased in the AIDS patients with weight loss (2.83 +/- 0.67 mumol/l) relative to the controls (1.31 +/- 0.13 mumol/l, P < 0.05), with the HIV + patients (1.65 +/- 0.18 mumol/l) and AIDS patients without weight loss (1.90 +/- 0.22 mumol/l) falling in between. The data are consistent with a low, but chronic rate of bacteria and/or bacterial products seeping across a compromised colonic wall causing a chronic low stress response in AIDS patients.
PMID: 9071566
CONCLUSIONS: Patients with AIDS and diarrhea have altered intestinal permeability. The decreased absorption of mannitol suggests that the functional absorptive surface of the intestine decreases as HIV disease progresses.
PMID: 8198098
These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease.
PMID: 8362208
Altered small-intestinal permeability is associated with symptomatic diarrhoea in human immunodeficiency virus infection in both Caucasian and African patients.
PMID: 1655333
Our results suggest that severe diarrhea may be uncommon in children with HIV infection receiving antimicrobial prophylaxis, but that the intestinal function is frequently, and often markedly, impaired.
PMID: 1865278
It really shocked when I read what influence HIV has on the gastrointestinal tract of humans. When not treated, this leads from diarrhea to pancreatic dysfunction and as a consequence to malabsorption and weight loss which in the end make it much riskier to die from a normal infection because the body has no more means to fight it off.
What really gives me hope is that HAART (highly active anti-retroviral therapy) normalizes everything. All the HIV patients who have extreme gastrointestinal problems (including increased intestinal permeability) improve on treatment till the gastrointestinal tract normalizes completely (!). I cannot say for sure of course but to me it looks much like we suffer from a viral disease! So if XMRV or other viruses are the cause of CFS this would perfectly fit into the picture since many of us have gastrointestinal problems.
Prof De Meirleir is using a test called "Immunobilan" which checks for IgAs and IgMs directed at intestinal bacteria. Positive results indicate a translocation of bacteria. The following study shows that this is also a problem with HIV:
Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation.
Collectively, our data shows that mucosal epithelial cells respond directly to envelope glycoprotein of HIV-1 by upregulating inflammatory cytokines that lead to impairment of barrier functions. The increased permeability could be responsible for small but significant crossing of mucosal epithelium by virus and bacteria present in the lumen of mucosa. This mechanism could be particularly relevant to mucosal transmission of HIV-1 as well as immune activation seen in HIV-1 infected individuals.
PMID: 20386714
Here are some more conclusions:
CONCLUSIONS: Suppressive HAART abrogates HIV-induced intestinal barrier defect and villous atrophy. The HIV-induced barrier defect is due to altered tight junction protein composition and elevated epithelial apoptoses. Mucosal cytokines are mediators of the HIV-induced mucosal barrier defect and villous atrophy.
PMID: 18936106
The digestive-absorptive functions are impaired, with steatorrhea, nutrient malabsorption, and increased permeability occurring in 20-70% of children.
PMID: 15612836
CONCLUSIONS: Cell-cell interaction of HIV-infected macrophages with PBMC leads to a release of cytokines sufficient to alter intestinal epithelial barrier function. The main effect was mediated by TNFalpha inducing a leak-flux which may contribute to the diarrhoea by HIV per se (HIV-enteropathy).
PMID: 11953464
CONCLUSION: Because systemic exposure of oral ganciclovir (Valcyte) is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.
PMID: 11015151
BACKGROUND: Impaired intestinal function could account for diarrhoea and weight loss, which are common features of advanced human immunodeficiency virus (HIV) infection.
CONCLUSIONS: These findings suggest a loss of intestinal functional absorptive surface as HIV disease progresses. This process may be present at the early stage of infection. Impaired intestinal permeability is observed later in AIDS patients when digestive signs are present, particularly diarrhoea.
PMID: 10048729
Weight loss, the gut and the inflammatory response in aids patients.
Stein TP, Koerner B, Schluter MD, Leskiw MJ, Gaprindachvilli T, Richards EW, Cope FO, Condolucci D.
Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford 08084, USA.
Abstract
The objective of this study was to test the hypothesis that the integrity of the large bowel wall in AIDS patients is compromised in a manner that favours the chronic translocation of bacteria and/or products of bacterial metabolism into the bloodstream. When such translocation occurs, it induces a characteristic stress/inflammatory response in the body. Urinary butyrate, a unique product of colonic microbial metabolism, was used to assess gut wall permeability. Excretion of the pro-inflammatory cytokine IL-6 in the urine was used as a marker for the stress/inflammatory response. Four groups of subjects were studied, controls (n = 12), HIV + (n = 35) and AIDS patients with (n = 14) and without (n = 17) weight loss. Results: measurable amounts of interleukin 6 (IL-6) and butyrate were found in the urine of all subjects. There were no significant differences in IL-6 excretion between the controls (0.68 +/- 0.64 pg/ml), asymptomatic HIV + subjects (0.59 +/- 0.37 pg/ml) and AIDS patients without weight loss (1.18 +/- 0.33 pg/ml) but IL-6 levels were significantly higher in the AIDS group with weight loss (4.02 +/- 1.26 pg/ml, P < 0.05). A similar pattern of results was found with interleukin 1 receptor antagonist (IL-1ra). Like IL-6 and (IL-1ra), urinary butyrate levels were increased in the AIDS patients with weight loss (2.83 +/- 0.67 mumol/l) relative to the controls (1.31 +/- 0.13 mumol/l, P < 0.05), with the HIV + patients (1.65 +/- 0.18 mumol/l) and AIDS patients without weight loss (1.90 +/- 0.22 mumol/l) falling in between. The data are consistent with a low, but chronic rate of bacteria and/or bacterial products seeping across a compromised colonic wall causing a chronic low stress response in AIDS patients.
PMID: 9071566
CONCLUSIONS: Patients with AIDS and diarrhea have altered intestinal permeability. The decreased absorption of mannitol suggests that the functional absorptive surface of the intestine decreases as HIV disease progresses.
PMID: 8198098
These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease.
PMID: 8362208
Altered small-intestinal permeability is associated with symptomatic diarrhoea in human immunodeficiency virus infection in both Caucasian and African patients.
PMID: 1655333
Our results suggest that severe diarrhea may be uncommon in children with HIV infection receiving antimicrobial prophylaxis, but that the intestinal function is frequently, and often markedly, impaired.
PMID: 1865278
