Researchers have shown for the first time how the gut microbiome can affect the immune system in humans, the population of microorganisms living in the gut. Their work may lead to new therapies for conditions that are immune-related.
Following treatment for blood cancers, researchers at the Memorial Sloan Kettering Cancer Center in New York, NY, monitored the recovery of patients’ gut microbiota and immune system following bone marrow transplants (BMTs).
To eliminate cancerous blood cells in conditions such as leukemia and lymphoma, healthcare professionals use chemotherapy and radiation therapy. Specialists inject patients with stem cells from the donor’s blood or bone marrow following completion of the procedure, which often destroys healthy immune cells.
These donated cells slowly regain the capacity of patients to produce blood cells of their own.
In the first few weeks after the transplant, though, patients have to take antibiotics because they are already vulnerable to infections. These disrupt their gut microbiota’s balance, destroying “friendly bacteria” and enabling hazardous strains to flourish.
Unique opportunity
Once the immune systems of patients are sufficiently healthy, they may stop taking antibiotics, allowing their gut microbiota to recover.
The researchers at Sloan Kettering used this rare opportunity to investigate how the immune system is affected by the microbiota.
The idea that the gut microbiota was critical for the health of the human immune system had already been recognized by the scientific community, but the evidence they used to make that inference came from animal studies,” explains system biologist Joao Xavier, co-senior author of the paper with former postdoc Jonas Schluter.”
“According to Dr. Schluter, who is now an assistant professor at NYU Langone Health in New York, NY, “The simultaneous recovery of the immune system and microbiota, both of which are weakened and then restored, gives us a rare opportunity to examine the interactions between these two systems.
The researchers were able to monitor everyday changes in their gut microbiota and the amount of immune cells in their blood using blood and fecal samples from more than 2,000 patients treated at the cancer center between 2003-2019.
Thousands of data points
Our research shows that biological samples that would literally be flushed down the toilet can learn a lot from the stool,” says Dr. Xavier.” “The result of gathering them is that we have a unique dataset that we can use to ask questions about the dynamics of this relationship with thousands of data points.”
To recognize trends in the data, the researchers used a machine-learning algorithm, which included details about the drugs of patients and the side effects they suffered.
One of the results was that three groups of intestinal bacteria, called Faecalibacterium, Ruminococcus 2, and Akkermansia, were associated with increased immune cell blood concentrations called neutrophils.
By comparison, reduced numbers of these immune cells were associated with two forms, called Rothia and Clostridium sensu stricto 1.
The researchers’ computer models projected that enriching microbiota with the three ‘friendly’ genera would accelerate the recovery of the immune systems of patients.
“By regulating the microbiota more closely, this research could ultimately suggest ways to make BMTs safer,” says co-author Marcel van den Brink.
The study appears in Nature.
Improved treatments
Concluding their paper, the authors write:
“Our demonstration that the microbiota influences systemic immunity in humans opens the door toward an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.”
A previous study showed that it is correlated with a better chance of survival after a stem cell transplant to provide a greater diversity of bacterial species in the gut. This study has showed that when the donor immune cells invade the recipient’s tissues, a low diversity of bacteria raises the risk of potentially lethal graft-versus-host disease.
The Sloan Kettering researchers released findings from a clinical trial in 2018 in which they used fecal transplants to restore the microbiota of patients following blood cancer treatment.
They used the patients’ own fecal matter, which had been extracted and frozen until their gut microbiota was disrupted by bone marrow transplantation and antibiotic therapy.
