Does Gut Microbiota Exacerbate HIV?

The human gastrointestinal (GI) tract is home to trillions of symbiotic microbes that benefit our body by aiding in digestion and outcompeting pathogenic microbes. The delicate balance between gut flora and the immune system is disrupted by chronic viral infections such as HIV. Chronic HIV infection is characterized by persistent immune activation and the continuous depletion of CD4+ helper T-cells. Recent studies have been exploring the gut microbiome’s role in HIV infection and have found that alterations to gut flora caused by HIV may have a role in exacerbating the disease. Namely, HIV causes damage to intestinal epithelia, allowing gut flora to enter the bloodstream and contribute to chronic immune activation. HIV may also be correlated with shifts in the gut floral community towards pathogenic microbes that could increase risks for disease and perpetuate HIV progression.


In a healthy individual, gut flora are diverse and highly variable and help the body establish gut-associated lymphoid tissue (GALT), a major portion of the human immune system and a major infection site for HIV. HIV rapidly depletes CD4+ helper T-cells in GALT, which causes damage to the intestinal epithelia, allowing microbes and their products to be 'leaked' or translocated into the bloodstream. This leakage has been linked to the development of AIDS as it is a contributing factor to chronic immune activation.

The initial effects of HIV also cause gastrointestinal inflammation, which may cause intestinal conditions that are more favorable to pathogenic microbes, resulting in a shift in the resident microbial community towards pathogenic microbiota that can perpetuate diseases and the proliferation of HIV. In a study by Vujkovic-Cvijin et al. (2013), HIV-positive patients were found to have gut flora enriched in Proteobacteria, a major group of bacteria which contains pathogenic genera such as Salmonella and Escherichia that are known to cause bacteremia and other diseases of the gut. They also displayed decreased Bacteroides bacteria which is known to have critical functions in the GI tract, further contributing to an unbalanced gut microbiome.

In addition, HIV-positive patients were found to have gut flora enriched with bacteria that have the capacity to catabolize Tryptophan through the Kynurenine (Kyn) pathway - a pathway that is relevant to HIV progression. HIV is associated with high levels of intracellular indoleamine 2,3-dioxygenase (IDO), an immune system enzyme that catabolizes the amino acid Tryptophan into Kyn. Kyn is an immunosuppressive metabolite that inhibits T cell proliferation. Increased IDO and Kyn levels have been linked to chronic high levels of immune activation in HIV patients. Bacteria with the capability to produce Kyn from Tryptophan can thus increases Kyn levels and exacerbate the progression of HIV. If translocated through the blood, these bacteria can also increase immune system effects in other organs of the body, leading to further complications (Fig. 1).

Figure 1. From: Vyboh, K., Jenabian, M., Mehraj, V., Routy, J. 2015. HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets. Journal of Immunology Research, 2015, Article ID 614127, <http://dx.doi.org/10.1155/2015/614127>.

Antiretroviral therapy helps to control the depletion of CD4+ T-cells in HIV patients but does not have the capability to alter GI microbial communities. Probiotics (live microorganisms) and prebiotics (indigestible food compounds that stimulate growth of beneficial gut microbes) can help to grow and diversify human microbiota to promote health and are useful in diseases involving gastrointestinal inflammation.

Since the GALT is a major site for HIV infection, understanding the link between damages caused by HIV and gut microbiota is crucial and may be a target for new methods to treat the disease. Currently, research is primarily correlational, and many mechanisms of the roles gut microbes play in HIV infection remain speculative. If more knowledge is gained about the complex interaction between HIV and microbiota, strategies that target both gut flora and HIV could be useful additions to current antiretroviral treatments.

References


Vujkovic-Cvijin, R. M. Dunham, S. Iwai, M. C. Maher, R. G. Albright, M. J. Broadhurst, R. D. Hernandez, M. M. Lederman, Y. Huang, M. Somsouk, S. G. Deeks, P. W. Hunt, S. V. Lynch, J. M. McCune. 2013. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci. Transl. Med. 5, 193ra91.





Vyboh, K., Jenabian, M., Mehraj, V., Routy, J. 2015. HIV and the gut microbiota, partners in crime: breaking the vicious cycle to unearth new therapeutic targets. Journal of Immunology Research, 2015, Article ID 614127, <http://dx.doi.org/10.1155/2015/614127>.