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Postbiotics: an emerging option for gut health

One of the compounds produced by Lactobacillus bacteria in the gut is lactate (or lactic acid). Lactate regulates stomach pH in a way that helps beneficial bacteria thrive and deters harmful species. Proponents of postbiotics hope to use microbes to create compounds, like lactate, outside of the gut and deliver them directly.© luismmolina/ iStock / Getty Images Plus

The link between health and gut bacteria is a growing field of research. Often it’s the compounds produced by gut bacteria metabolisms that are most pivotal. Among the existing ways to manage these compounds are probiotics, which introduce more beneficial microorganisms into the body, and prebiotics, which feed helpful bacteria in the gut. Now ‘postbiotics’ are emerging as an option. Although the international community is still building a consensus on the term’s exact definition, postbiotics broadly refers to attempts to deliver pre-converted metabolic compounds straight to the gut, without a person’s own bacteria as an intermediary.

“Sometimes, one may not have the right microbial profile to benefit from the interaction between their bacteria and probiotics or prebiotics,” explains Kazuya Mitsuhashi, an R&D Manager at chemicals manufacturer, Daicel Corporation. Microbial composition varies, affected by factors such as gender, age, eating habits, and stress levels.

“Postbiotics are about delivering compounds to the gut without being affected by the presence or absence of a particular microbe,” says Mitsuhashi. While probiotics and prebiotics may help cultivate healthy gut fauna, postbiotics could meet a more immediate need, he adds.

Equalizing equol

Mitsuhashi points to the example of soy isoflavone, an ingredient found in soybeans. Small studies have shown that soy isoflavone may contribute to women’s post-menopausal health when intestinal bacteria convert it to equol, a compound similar in structure to estrogen. These papers showed equol functioning much like a weak alternative to estrogen, and a 2018 meta-analysis concluded that effective supplementing of equol significantly reduced the severity and incidence of hot flashes in peri- or postmenopausal women.

A Daicel researcher operates a 30 litre jar fermenter as part of a study on how to scale-up production of equol.© 2021 Daicel Corporation

Studies in the early 2010s, however, revealed that somewhere between only 30-60% of the Japanese population were capable of producing equol from soy isoflavone. The proportion appeared even lower in young Japanese women, at 20-30%. “It’s fair to say that more than half of the people consuming soy isoflavone products may have been unable to obtain the intended benefits to start with,” says Mitsuhashi.

Daicel hopes to use bioproduction to overcome this issue. Drawing on 40 years of experience in handling microbes, Daicel brought converted equol to the market in 2014. “We modelled the fermentation process that occurs in the gut to manufacture our equol,” explains Mitsuhashi. Through revisiting a prior project that used anaerobic bacteria to manufacture acetic acid, an organic compound used in many solvents and cellulose plastics, the Daicel team recreated an anaerobic environment similar to the gut in a fermentation tank filled with bacteria. Their product is used as a raw ingredient of some supplements.

Recycling mitochondria

In a similar line of work, Daicel is preparing to commercialize urolithin A, derived from the ellagic acid found in pomegranate, nuts, and berries. “Urolithin A was the first postbiotic compound shown to induce mitophagy, in which the body destroys old or damaged mitochondria to recycle proteins for new cells,” Mitsuhashi explains, referring to a 2016 Nature Medicine paper by Swiss researchers using animal models. “Mitophagy is powerful, as the mitochondria are essentially the cell’s powerhouse – a cell’s energy production worsens when the mitochondria become degraded.” The paper showed that in C. elegans, urolithin A extended lifespan and prevented loss of activity due to ageing; the compound also had positive effects on mice, improving muscle function.

“While it’s clear that the compound plays a role in energizing the cell, there are numerous possibilities as to how this would affect health in visible terms,” notes Mitsuhashi. A flurry of mouse studies published in high-impact journals in 2019 suggest that urolithin A might be able to significantly improve sensitivity to insulin, cognitive function in those with Alzheimer’s disease and gut barrier function. The latter, published in Nature Communications, has implications for overall gut health and inflammatory bowel diseases if further validated in clinical trials, for example.

A Daicel researcher works with microbes in a safety cabinet.© 2021 Daicel Corporation

But unlike equol, producing urolithin A involves a complex chain of chemical reactions involving a multitude of intermediates. In 2016, the Daicel team had a breakthrough when they discovered of two kinds of bacteria, each playing a role in different subsets of the chemical reaction. These are now both used to help produce the compound. With a manufacturing process in place, Daicel is working with clients to assess the quality of their urolithin A delivering products.

Among other nascent projects, Daicel is investing in compounds derived from hop, known for its use in beer. Hops contain pre-estrogenic compound xanthohumol, which will be converted to 8-prenylnaringenin in gut. 8-prenylnaringenin is another compound shown to have strong estrogen-like properties. Mitsuhashi’s team succeeded in isolating bacteria that converts another abundant compound in hops into 8-prenylnaringenin. “That was a huge leap towards mass production. But at this moment, we are still exploring the specific functions of this compound,” he notes.

While postbiotics may be unnecessary for those lucky enough to have a very productive microbiome, says Mitsuhashi, they could help support those who are struggling with their gut health. “Ultimately, the choice of whether to take probiotics, prebiotics or postbiotics should rest with the consumer,” he says. “Our mission is to provide options, so that ready access to potentially beneficial gut compounds is available, regardless of the types of bacteria thriving in an individual’s gut at any one time.”


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