A new study conducted in Israel and Ethiopia, led by researchers from the Weizmann Institute of Science and Hadassah University Medical Center, found that gut bacteria can strengthen CD4 cells in the intestine after infection, but the effect weakens in advanced stages – a finding that may open new treatment directions.
The following study was conducted under particularly extreme circumstances. One of its leaders was forced to flee his homeland, which had become a war zone, and more than two thousand kilometers away, the research team leader's laboratory was destroyed by a ballistic missile strike. Despite all this, and after almost a decade of work in Ethiopia and Israel, the project reached the finish line with encouraging news. Among the findings Those who are published in the scientific journal Nature Microbiology It appears that in people living with HIV, gut bacteria reach out and boost the immune system that is under attack. These discoveries may make it possible to harness gut bacteria in a targeted manner to protect against infections that occur as a result of immune failure.
The research team was actually headed by two people – Prof. Eran Alinev, whose lab at the Weizmann Institute of Science was among the labs hit in the Iranian attack on Israel in June 2025, and Prof. Hila Elinav, an infectious disease specialist and director of the AIDS Medicine Unit at Hadassah University Medical Center. The two are not only research partners but also life partners who first met as young medical students.
Their choice to conduct the study in two very different environments, Israel and Ethiopia, stems from the fact that the microbiome – the community of bacteria that inhabits our intestines – is influenced by many factors, including genetics, diet, lifestyle and sanitation. Finding similar patterns in the microbiomes of different and distant populations reinforces the assumption that the patterns found represent general biological principles and are not local or random phenomena.
Ethiopia was a natural choice, as for the past thirty years, Prof. Hila Elinav and her predecessor, Prof. Shlomo Maain, have maintained close ties with the Ethiopian health system, especially in the Tigray region in the north of the country, which is struggling with poverty and ongoing civil war. As part of these ties, Hila has volunteered at a clinic in the city of Mekelle, the regional capital, and members of the Hadassah AIDS Medicine Unit team have conducted joint research and programs with Ethiopian scientists and doctors.
"Even when the immune system recovers throughout the body as a result of effective HIV drug treatment, T cells in the intestinal mucosa do not fully recover."
Dr. Jamal Ali Mahdi, one of the study's leaders, comes from the Tigray region. When the study began, he was a PhD student at Ben-Gurion University of the Negev and joined Prof. Eran Elinav's lab at the Weizmann Institute as a visiting student. Mahdi is one of five first authors of the study – alongside Dr. Stavros Bashyards, Dr. Melina Heinemann, Dr. Lorenz Adelung and Dr. Rafael Valdes Mas – and was responsible for collecting samples in Ethiopia in collaboration with the local medical team. Shortly after he returned to his homeland, a civil war broke out in the region, and he was forced to flee to the United States. Despite the real danger, he later returned to Ethiopia to help complete the study.
When gut bacteria fight back
For almost three decades, effective drug treatment has been available that allows those infected with HIV to live with the virus in almost the same way as those who do not carry the virus. This has transformed HIV, especially in Western countries, from a terminal illness to a chronic condition. Drug treatment does prevent a state of immune failure, but the virus does not disappear completely: even when it can no longer be detected in the blood of carriers, a state known as undetectable, the virus still survives in the body and its main hiding place is the intestinal mucosa – an area particularly rich in immune system cells.
"Even when the immune system recovers throughout the body as a result of effective HIV drug treatment, the T cells in the intestinal mucosa do not recover completely due to the presence of the virus in the intestine," explains Prof. Hila Elinav. "Therefore, it was particularly relevant to examine the interrelationships between intestinal bacteria and immune system cells in people living with HIV."
To do this, the research team analyzed the composition of the microbiome in stool samples collected at different time points over a decade from about 70 HIV carriers in Israel and a similar number of carriers in Ethiopia. In both countries, the scientists compared the composition of the gut bacteria in the carriers with control groups consisting of Israelis or Ethiopians who were not carriers. All carriers in the study were treated with HIV drugs, but Ethiopia lacked most of the newest drugs that are given to carriers in Israel.
In addition to monitoring gut bacteria, the researchers also measured levels of immune system cells called T-helper cells or CD4 cells – the main cells that HIV attacks. The virus damages these cells, and in the absence of treatment, their numbers can drop to levels that allow the emergence of infections and diseases that characterize acquired immunodeficiency syndrome, or AIDS.
The researchers found that the composition of gut bacteria in people living with HIV was different from that in people without the virus. Moreover, the longer the time passed since infection and the lower the CD4 cell count, the more pronounced the changes were – dozens of bacterial strains disappeared, while others multiplied. Some of the changes in the microbiome were common to both Ethiopian and Israeli carriers, and likely reflect a universal phenomenon, while other changes were unique to one country and likely indicate differences in diet and lifestyle. But how does infection with a virus that attacks the immune system in general lead to changes in the microbiome?
"The intestinal bacteria act here as a kind of immune organ – they are both affected by the immune system and influence it."
"Immune system cells continuously shape the composition of gut bacteria through the secretion of antimicrobial molecules," explains Prof. Eran Elinav. "Because HIV attacks the immune system, the secretion of these molecules changes, and accordingly the composition of gut bacteria changes - some are suppressed while others thrive. In the new study, we also tried to understand whether this effect is reciprocal - that is, do gut bacteria also affect the immune system following the infection?"
To test this question, the scientists transferred the gut bacteria of HIV-infected subjects and control subjects to mice that had been raised without any gut bacteria at all, or whose microbiome had been significantly depleted with antibiotics. Since the mice are not infected with HIV, any changes in their immune systems were directly due to the composition of the bacteria and not to any effect of the virus.
The results surprised the researchers: The gut bacteria of HIV carriers increased the levels of CD4 cells in the intestines of the mice, bringing them to levels that were even higher than in the control group. The surprising finding suggests that the gut bacteria compensate for the damage caused by the virus to the immune system and increase the attacked population of CD4 cells in the intestines. However, at a certain point in the progression of the disease, the compensatory effect reaches its limit – when the mice were transferred with gut bacteria from participants whose condition had progressed to severe immunodeficiency and AIDS, their microbiome composition failed to provide immune support and the mice exhibited lower levels of CD4 cells.
Finally, the scientists tested whether the bacteria's support for CD4 cells might also actually protect against infections that occur in a state of immunodeficiency. They showed that mice that received gut bacteria from HIV carriers and developed higher levels of CD4 cells were indeed able to cope faster and better with a parasite that causes a common disease in states of immunodeficiency. In contrast, mice that received gut bacteria from humans who were already immunodeficiency coped less well with the parasite. These results indicate that gut bacteria can strengthen the immune system and reduce the risk of infections - provided that the disease has not crossed a certain threshold.
These findings are important on two levels. "At the basic science level, our study presents strong and initial evidence for a mutual influence between gut bacteria and the immune system in humans," says Prof. Eran Elinav. "In effect, gut bacteria behave here as a kind of immune organ – they are both influenced by the immune system and influence it."
The findings may also have important implications at the clinical level. Unlike genetics, the microbiome can be modified – through diet, tailored probiotics, molecules secreted by bacteria or even bacteriophages – viruses that selectively attack certain bacteria. “Much research is still needed to identify which bacteria and molecules are involved,” says Prof. Hila Elinav. “But our study shows that in the future it may be possible to support the immune system of people with HIV using gut bacteria and thereby reduce their exposure to life-threatening infections.”
Also participating in the study were Dr. Samuel P. Nobbs, Dr. Timur Tuganbab, Dr. Takehiro Yamada, Max Horn, Oriya Mor, Yotam Cohen, Dr. Muhammad Darvish Arslan, Shahar Molina, Maya Tzur, Shmarit Eliyahu Miller, Orali Rose Bukimer Mimran, Dr. Sarah Federici, Dr. Mali Dori-Bakhsh, Dr. Nira Amar and Dr. Hagit Shapira from Prof. Eran Elinav's laboratory in the Institute's Department of Systemic Immunology and Prof. Ido Amit from the same department; Dr. Sarah Israel, Prof. Maya Korem, Dr. Jonathan Oster, Dr. Keren Olstein-Pops and Dr. Efrat Ornbuch-Harash from the AIDS Medicine Unit at Hadassah University Medical Center; Dr. Daniel Albirt from Kaplan Medical Center; Dr. Ronit Cohen-Forduso, Prof. Dan Turner and Dr. Niv Zamora from Sourasky Tel Aviv Medical Center (Ichilov); Dr. Tiberio Hershkowitz and Dr. Elez Weiner from Hadassah University Medical Center; Dr. Noa Stettner and Prof. Alon Hermlin from the Department of Veterinary Resources of the Weizmann Institute; Dr. Hayley Gebermeskel and Dr. Yazazu Kebede from Mekelle University, Ethiopia; Dr. Sabine Schmidt, Dr. Aronraj Damodaran and Dr. Jens Fuschhoff from the German Cancer Research Center (DKFZ), Heidelberg, Germany; and Prof. Zvi Bentoitz from Ben-Gurion University of the Negev.
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