The mechanism involves a cell receptor called HCA3. A cell receptor is a protein that allows specific signals to enter cells when a matching molecule binds to it.
While scientists have known about HCA3 for several years, it was not clear what role it played. Only humans and great apes have the HCA3 receptor. Other mammals, such as mice, do not.
Now a team from the University of Leipzig in Germany, together with other colleagues, have discovered that HCA3 is receptive to a particular metabolite, or byproduct, of lactic acid bacteria activity.
The metabolite has the name D-phenyllactic acid (D-PLA). When it binds to HCA3, it triggers a signal that alerts the immune system to the presence of the bacteria.
The researchers describe their findings in a recent PLOS Genetics study paper.
“We are convinced,” says senior study author Claudia Stäubert, who works in the Medical Faculty at the University of Leipzig, “that this receptor very likely mediates some beneficial and anti-inflammatory effects of lactic acid bacteria in humans.”
Lactic acid bacteria and fermented foods
Lactic acid bacteria are microbes that can ferment certain foods. For example, they can produce yogurt from milk and sauerkraut from cabbage. They are also present in the gut of most mammals.
The bacteria belong to a large group of “functional microorganisms” that ferment foods from plant and animal sources. These microbes alter food in many ways that humans make use of and are beneficial to health.
Not only can fermentation microbes alter the texture, flavor, and aroma of food, they also extend storage life through preservation, increase absorption of nutrients, break down toxins, stimulate probiotic activity, and produce antioxidants.
Research has shown that consuming fermented foods brings health benefits that are relevant to cancer, heart disease, allergies, diabetes, and gastrointestinal disorders.
However, while many studies have linked lactic acid bacteria to various health benefits, there is little understanding of the underlying biology.
Stäubert and her colleagues investigated this question by exploring the role of hydroxycarboxylic acid (HCA) receptors. These receptors, note the authors, “are regulators of immune functions and energy homeostasis under changing metabolic and dietary conditions.”
Evolutionary history of HCA3 receptor
Most mammals have two HCA receptors: HCA1 and HCA2. However, humans and great apes have a third — HCA3.
In their study paper, the researchers explain how they “reconstructed the evolutionary history” of HCA receptors and showed that it is “functionally present in humans and all other great apes.”
They discuss how lactic acid bacteria were already fermenting animal and plant materials long before humans “took advantage” of the process.
A long time ago, there was a significant global change that affected the “last common ancestor of early hominoids.” It is likely that this change disrupted eating habits, so that fermented fruits and leaves entered the diet at around this time.
Could it be that HCA3 started as a gene copy error that offered a survival advantage to human ancestors who passed it on?
The researchers suggest that their findings support the idea “that increased intake of [food fermented by lactic acid bacteria] likely posed a positive selective pressure maintaining HCA3 function in hominids.”
They also propose that the presence of HCA3 may have helped to foster interactions between ingested and gut microbes by “taking over functions in the immune system.”
New light on microbe-host evolution
To sum up, the study sheds new light on how certain microbes — such as those that ferment food and live in the gut — and humans evolved together.
It could stimulate further research on how to use the biological mechanisms through which fermented foods benefit health.
For example, in the case of HCA3, Stäubert says that she and her colleagues “believe it could serve as a potential drug target to treat inflammatory diseases.”
The team suggests that future studies should investigate how D-PLA affects the immune system. They should also explore whether the metabolite impacts other cells that carry HCA3, such as fat cells.