Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism.

Progressive HIV infection is characterized by dysregulation of the intestinal immune barrier, translocation of immunostimulatory microbial products, and chronic systemic inflammation that is thought to drive progression of disease to AIDS. Elements of this pathologic process persist despite viral suppression during highly active antiretroviral therapy (HAART), and drivers of these phenomena remain poorly understood. Disrupted intestinal immunity can precipitate dysbiosis that induces chronic inflammation in the mucosa and periphery of mice. However, putative microbial drivers of HIV-associated immunopathology versus recovery have not been identified in humans. Using high-resolution bacterial community profiling, we identified a dysbiotic mucosal-adherent community enriched in Proteobacteria and depleted of Bacteroidia members that was associated with markers of mucosal immune disruption, T cell activation, and chronic inflammation in HIV-infected subjects. Furthermore, this dysbiosis was evident among HIV-infected subjects undergoing HAART, and the extent of dysbiosis correlated with activity of the kynurenine pathway of tryptophan catabolism and plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), two established markers of disease progression. Gut-resident bacteria with capacity to catabolize tryptophan through the kynurenine pathway were found to be enriched in HIV-infected subjects, strongly correlated with kynurenine levels in HIV-infected subjects, and capable of kynurenine production in vitro. These observations demonstrate a link between mucosal-adherent colonic bacteria and immunopathogenesis during progressive HIV infection that is apparent even in the setting of viral suppression during HAART. This link suggests that gut-resident microbial populations may influence intestinal homeostasis during HIV disease.

Positive contrast magnetic resonance bursography for assessment of the navicular bursa and surrounding soft tissues.

Magnetic resonance (MR) imaging is often performed to determine the cause of palmar heel pain. We evaluated how distension of the navicular bursa affected the MR appearance of the navicular bursa and associated structures. An MR evaluation was performed on normal cadaver limbs and cadaver limbs from horses with lameness localized to the foot. The normal navicular bursae were injected with 2, 4, or 6 ml of solution. The bursae of the feet from lame horses were injected with 4 or 6 ml, and the MR study was repeated. All bursae were examined grossly to verify the presence or absence of adhesions. Clinical patients that had initial MRI abnormalities suggesting adhesions were also evaluated. Distension of the proximal recess of the normal navicular bursa, proximal to the collateral sesamoidean ligament was achieved with 2 ml. Separation of the collateral sesamoidian ligament from the deep digital flexor tendon (DDFT) was achieved with 4 ml. The separation of the navicular bone from the DDFT and distal sesamoidian impar ligament required 6 ml. Adhesions were more clearly defined in the bursa of the two pathologic cadaver limbs following distension. MR bursography used on clinical patients allowed the determination of the presence or absence of adhesions. In these horses, this determination could not have been definitively made without this technique. MR bursography is useful in horses where the presence of adhesions cannot be clearly defined by MRI.