Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil

Abstract

Objectives: To determine the relative effects of AIDS-related diarrhea with or without cryptosporidiosis and microsporidiosis on intestinal function and injury.

Methods: We studied 40 HIV-infected patients (20 with and 20 without diarrhea) and 13 healthy volunteers, using the differential urinary excretion of ingested lactulose and mannitol as respective markers of barrier disruption and overall villous surface area. We also examined them for fecal leukocytes, lactoferrin, and alpha 1-antitrypsin. Fasting subjects drank test solution containing lactulose (5 g) and mannitol (1 g). Urine was collected for 5 h and tested for sugars by high-performance liquid chromatography with pulsed amperometric detection.

Results: HIV-positive patients with diarrhea had a 2.8-fold higher lactulose:mannitol excretion ratio (L:M) than HIV-positive patients without diarrhea (p = 0.01) and 10.4-fold higher than healthy volunteers (p = 0.004). This was accounted for by a 1.5- to 3.1-fold higher rate of lactulose excretion by HIV patients with diarrhea than by those without diarrhea or by healthy volunteers. Mannitol excretion was 32-55% less in patients with diarrhea than in those without diarrhea or in healthy volunteers. Patients with cryptosporidial diarrhea had a nearly 6-fold higher L:M ratio than those without diarrhea (p < 0.001) and nearly 3-fold higher than those with non-cryptosporidial diarrhea (p = 0.02). One patient with microsporidial infection had a nearly 3-fold higher L:M ratio than controls without diarrhea. Alpha 1-Antitrypsin was positive in 40% of HIV-positive patients with cryptosporidial infections and none of 12 HIV-positive patients with non-cryptosporidial diarrhea. Fecal lactoferrin or leukocytes were increased in all HIV patients with diarrhea.

Conclusion: HIV infection is associated with intestinal dysfunction and injury, even in patients who do not have diarrhea. However, those with diarrhea, especially with cryptosporidiosis or microsporidiosis, have even greater disruption of intestinal barrier function with potentially important nutritional consequences.

PIP: The effects of AIDS-related diarrhea--with and without cryptosporidiosis and microsporidiosis--on intestinal function and injury were studied in 40 AIDS patients and 13 healthy volunteers from Fortaleza, Brazil. The differential urinary excretion of ingested lactulose and mannitol was used as a marker of barrier disruption and overall villous surface area. HIV-infected patients with diarrhea had a 2.8-fold higher lactulose to mannitol excretion ratio than HIV-positive patients without diarrhea and a 10.4-fold higher ratio than healthy volunteers. Moreover, those with crypotosporidial infection had a lactulose to mannitol ratio almost 6-fold greater than those without diarrhea and nearly 3-fold higher than those with non-cryptosporidial diarrhea. This effect involved both decreased mannitol excretion (decreased intestinal absorptive area) and increased lactulose excretion (mucosal barrier disruption). The single patient with microsporidial infection had a nearly 3-fold higher ratio than healthy volunteers. Alpha1-antitrypsin tests were positive in two of five (40%) HIV-positive patients with cryptosporidial infections compared with none of 12 HIV-infected patients with non-cryptosporidial diarrhea. These findings confirm that HIV infection is associated with profound intestinal dysfunction and injury, even in those without diarrhea. Disruption of the intestinal barrier is even greater, however, in HIV-infected patients with cryptosporidial diarrhea, with potential nutritional consequences.