Microbial products in the blood promote chronic inflammation in patients with HIV
International team of researchers including scientists from Universitätsklinikum Erlangen conduct fundamental research into HIV
Although patients with human immunodeficiency virus (HIV) can benefit from treatment that suppresses the virus and thus protects them against the life-threatening acquired immune deficiency syndrome (AIDS), they usually have more health problems than people not affected by the virus and their life expectancy is lower. New studies indicate that increased and ongoing inflammation could be the cause.
An international team of researchers led by Dr. Christiane Krystelle Nganou Makamdop at Universitätsklinikum Erlangen at FAU and Dr. Daniel Douek from the National Institutes of Health (USA) has now identified microbial products from the intestines, such as parts of bacteria, that enter the bloodstream during a HIV infection and promote increased inflammation. This discovery could pave the way for reducing inflammation in patients with HIV by making these microbial products the target of potential future treatments. The research team has published its results in the journal Cell.
Patients with HIV often suffer from chronic inflammation that can cause permanent damage to the body. One mechanism that contributes to this inflammation is when the HI virus damages intestinal tissue leading to what is known as a leaky gut. Microbes from the intestines or parts of these microbes enter the bloodstream during a process known as microbial translocation. These intruders cause the damaging inflammation in the body. In addition, the composition of the microbes in the intestines of HIV patients is different to that of healthy people, with increased numbers of pathogenic bacteria. Even despite treatment using combination antiretroviral therapy (cART), which suppresses the HI virus, patients with HIV still suffer from increased chronic inflammation and microbial translocation. Precisely how microbial translocation promotes and prolongs inflammation in patients with HIV was not fully understood until now. The team of researchers led by Dr. Nganou Makamdop at the Chair of Clinical and Molecular Virology set to work to find the solution.
Intestinal microbiome triggers inflammation
Over a period of two years, the researchers tested blood samples of HIV patients from Uganda after they had started treatment with cART. In the blood samples, they found microbial products that originate in the intestines and are known as the translocated microbiome. In addition, the immune cells found in the blood provided information about when the cells reacted to their environment. The researchers discovered that the translocated microbiome changed during the course of the cART. There was an increased number of bacteria that could potentially cause higher levels of inflammation. The inflammation persisted for a longer period of time and had an adverse effect on the metabolism of the immune cells. The researchers checked their findings by exposing immune cells from the blood samples to the bacteria that promote inflammation, and obtained similar results. In addition, Dr. Nganou Makamdop observed that there was also a link between the translocated microbiome and the occurrence of inflammation in other HIV patients from Uganda, Canada and the USA.
These findings could have an impact on the treatment of HIV patients who suffer from chronic inflammation. The inflammation could perhaps be kept under control by using substances to neutralise the microbes and their products that enter the blood via the intestines. However, further studies are required to prioritise which components should be targeted in order to develop treatments.
Dr. Christiane Krystelle Nganou Makamdop
Chair of Clinical and Molecular Virology
Phone: +49 9131 8522678