The ways in which the communities of bacteria living within our bodies influence our overall well-being are becoming better understood all the time, and with that better understanding comes potential new ways to intervene for better health outcomes. Adding to this is a new discovery by researchers in Melbourne, who have described how a healthy microbiome can boost the activity of killer immune cells that are vital to fighting off infections and cancer.
A string of discoveries over the past few years alone have uncovered interesting links between the microbial communities that call the human body home and its overall health. These bunches of bacteria and the metabolites they produce have been linked to obesity-related depression, PTSD and Alzheimer's, diabetes and autism, and a team of researchers at the University of Melbourne looked to expand on this by investigating their links with the immune system.
More specifically, they sought to learn how the microbiome can drive the development of memory T cells, which are immune cells that have evolved to quickly recognize dangerous pathogens that threaten the body and swiftly spring into action to kill them off.
"We were trying to understand how the microbes that live in and on us influence our ability to form killer memory cells," associate professor Sammy Bedoui explains to New Atlas. "We addressed this question in preclinical mouse models, where we compared mice that did to those that did not have microbiota. We found that in the absence of microbiota, killer T cells failed to survive as memory cells. The reverse was true in mice with microbiota that we fed a high-fiber diet, akin to eating All-Bran or muesli. Here we found that more production of particular metabolites by the microbiota enhanced the ability of killer cells to survive and form memory cells."
The metabolites in question are short-chain fatty acids (SCFAs), and the team found that these can infiltrate the body's lymph nodes and spleen to influence the way the T cells use their energy, allowing them to sustain themselves for longer.
"These SCFAs change the way that the killer cells utilize fuels for energy generation," Bedoui tells us. "More specifically, they allow the killer cells to reduce their reliance on sugar and instead allow them to burn fats. This is critical for their long-term survival. Cells that only rely on burning glucose fail to survive."
Conveniently, the memory T cells that are aided by this healthier microbiota have shown great promise in cancer immunotherapy. This branch of cancer treatment and research focuses on supercharging the body's own immune system to take the fight to the disease, with ramping up the activity of T cells a particularly promising avenue of attack.
Much of the research around microbiome and human health focuses specifically on gut bacteria (though other communities, such as that found on the skin, have also produced some interesting discoveries). Bedoui tells us they are yet to precisely pinpoint the origins of the beneficial SCFAs, though the signs point to the gut playing an important role.
"We have not formally distinguished whether our effects are solely mediated by the gut microbiome," he says. "What points to it, however, is that the high-fiber diet has such a dramatic effect. So, we would suggest that the gut microbiome is critical, but it is also possible that the microbiome of other sites, like the skin, lungs, etc. may also play an additional role."
Although this link has only been demonstrated in mouse models so far, the team describes the discovery as "very exciting" and is hopeful it can lead to new drugs that improve the effectiveness of cancer immunotherapies. The timeframe for the development of synthetic versions that replicate these effects is unclear, however.
"We are working on this at the moment," says Bedoui. "It is too early to answer, but because we now understand the function of these naturally occurring substances, we can use this 'functional fingerprint' and test large collections of chemical compounds for their ability to induce similar changes."
The research was published in the journal Immunity.
Source: University of Melbourne (PDF)
