Scanning electron micrograph of Escherichia coli, one of the many bacteria in our gut. Bacteria like ... [+]
The host of symbiotic microbes in our gut has been in the news lately. The trillions of bacteria, viruses and fungi that live in our gut, collectively known as our microbiome, turn out to be critical to our overall health.
Without this gut flora, we would die.
Poor diet, overuse of antibiotics, and some diseases can kill off some of the good guys and bring up some of the bad guys, hurting our immune system and making us susceptible to diabetes, certain cancers, and even brain dysfunction.
So it was really amazing to see that this gut microbiome can also protect us from radiation.
Researchers at the UNC Lineberger Comprehensive Cancer Center, along with researchers at Duke, Sloan Kettering and Cornell, have shown that mice exposed to lethal doses of total body radiation (8.0 - 9.2 Gy) were protected from radiation damage if they had specific types of bacteria in their gut.
High levels of radiation (>0.2 Gy) can cause damage to tissues that may not be repaired quickly enough, resulting in damage or death. In this study, the bacteria mitigated radiation exposure and enhanced the recovery of blood cell production as well as repair of the gastrointestinal tract, indicating a crucial role for the gut microbiota as a master regulator of host defense against radiation, capable of protecting both the hematopoietic and gastrointestinal systems.
The researchers found that mice who had a high abundance of two types of bacteria, Lachnospiraceae and Enterococcaceae, in their guts strongly countered the effects of intense radiation. These two types of bacteria occur in humans and are abundant in leukemia patients with mild gastrointestinal symptoms who underwent radiotherapy.
The study by Hao Guo and colleagues showed that the presence of these two bacteria led to an increased production of small bacteria-derived metabolite molecules like propionate and tryptophan (figure below). These metabolites provided long-term protection from radiation, tuning the host resistance against high doses of radiation, by facilitating hematopoiesis and gastrointestinal recovery, lessening damage to bone marrow stem cell production, mitigating the development of severe gastrointestinal problems and reducing damage to DNA.
Gut microbes, especially Lachnospiraceae and Enterococcaceae, tune host resistance against high ... [+]
Interestingly, both of these metabolites are routinely purchased as health supplements although there is currently no evidence that the supplements act in the same way as these molecules act with the live biota in the gut.
"This truly trans-UNC collaborative effort showed that these beneficial bacteria caused a profound change in gut metabolites," said corresponding author and lead researcher Jenny P.Y. Ting, PhD, the William Rand Kenan Professor of Genetics in the UNC School of Medicine.
Damage to bodily organs from high levels of radiation, either from accidental exposure, cancer radiotherapy, or targeted radiation attacks, could lead to serious illness and even death. Blood cells in the body as well as tissues in the GI tract renew quickly, types of cells known as differentiating cells, and are particularly susceptible to radiation damage.
It should be noted that low levels of radiation do not cause such damage. In fact, this may be one of the reasons that radiation levels below 10 rem (0.1 Sv, equivalent to 0.1 Gy) do not increase cancer rates in any population.
Speculating, these mechanisms may date from the emergence of the eukaryotic cell and multicellular organisms about 2.3 billion years ago, or even earlier, when background radiation levels were about ten times higher than at present.
On the protective side, however, the 10 trillion microbial microorganisms hosted by the GI tract look to play an important role in limiting radiation-induced damage.
"Substantial federal efforts have been made to mitigate acute radiation symptoms - however, it remains a long-standing and unresolved problem," said lead author Hao Guo, PhD, a postdoctoral fellow in Ting's lab. "Our work produced a comprehensive dataset of bacteria and metabolites that can serve as a powerful resource to identify actionable therapeutic targets in future microbiome studies."
Because some radiotherapy procedures use high levels of radiation to treat cancer and can lead to GI side-effects, these investigators wanted to understand how their experiments in mice could translate to people. They worked with colleagues at Duke University, Memorial Sloan Kettering and Weill Cornell Medical College, and studied fecal samples from 21 leukemia patients due to receive radiation therapy as part of an arduous stem cell transplant conditioning.
The scientists found that patients with shorter periods of diarrhea had significantly higher abundances of Lachnospiraceae and Enterococcaceae than patients with longer periods of diarrhea. These findings correlated closely with the researcher's findings in mice although Ting cautions that much larger studies are needed to verify these conclusions in humans.
Importantly for potential human use, in mice that were supplemented with Lachnospiraceae, the benefits of cancer radiotherapy were not lessened.
"Granulocyte-colony stimulating factor is the only drug that has been approved by the FDA as an effective countermeasure for high-dose radiation exposure, but it is expensive and has potential adverse side-effects," said Ting. "However, bacteria that we can cultivate, and especially metabolites that are relatively inexpensive and already elements in the food we eat, may be a good alternative."
This research may lead to probiotic-ingestion preventive treatments for radiation and nuclear workers, rad techs, nuclear medicine workers and others handling radioactive materials, not that these groups have had any problems thus far.
The researchers are hoping to launch a clinical trial soon in people to test the benefits of giving these metabolites to patients receiving radiation treatment.
