Modern medicine has spent the past few decades rediscovering the connection between a healthy gut and a healthy mind and body, something traditional Chinese medicine (TCM) practitioners have understood for many hundreds of years.

In China and around the world, doctors and scientists trained in Western medicine have learned the importance of maintaining a balance between “good” and “bad” bacteria in the human microbiome – the scientific name for the collection of microorganisms in the gut – and what can happen to the body if an imbalance develops.

There is a new-found appreciation for the importance of the gut-brain axis through which gut bacteria produce neurotransmitters such as serotonin that directly affect mood, cognition and mental health. Western medicine experts have also explored the links between a healthy microbiome and healthy skin.

What’s more, they have identified naturally occurring strains of microorganisms called probiotics – mostly bacteria and yeasts – that can restore healthy microbial balance, and learned how to engineer them to deliver smart treatments for a variety of conditions, including cancer.

Chinese researchers have seen how fermenting TCM ingredients with probiotics can make their active substances easier to absorb and release new ones. And they have investigated the health gains from restoring microbiome balance through stool transplants, building on ancient TCM practice.

Around the world, interest in microbiome-based treatments is surging, with clinical trials exploring probiotics to treat conditions ranging from depression to Parkinson’s disease.

At stake is a global market that was estimated at just over US$900 million in 2023 and is forecast to grow to US$31.5 billion by 2030, according to Dublin-based Research and Markets.

Receptiveness to probiotics is high in China. In 2024, 81 per cent of consumers bought a product containing probiotics, according to a survey by global market research firm FMCG Gurus. Beyond digestive health and immune system support, consumers associate probiotics with good skin, joint and bone strength and heart health, the survey found.

The term probiotic means “for life”, combining the Latin , meaning for, and the Greek (life). Probiotics can inhibit the growth of harmful intestinal bacteria and relieve symptoms of diarrhoea and constipation, help the body’s immune system function better, prevent allergies and alleviate allergic reactions, and lower cholesterol and blood pressure.

Scientists extract these health-promoting microbes from human and animal guts, breast milk, fermented foods and dairy products and reprogram them to treat a wide range of ailments. In China this has produced world-leading breakthroughs.

Researchers at East China Normal University in Shanghai engineered a strain of probiotic gut bacteria, Nissle 1917 that could make type 2 diabetes care as simple as drinking a cup of yogurt or swallowing a capsule. The strain is named after the First World War German doctor who isolated it from the stools of a healthy soldier amid a diarrhoea outbreak. In tests on animals, the engineered probiotic performed on par with the blockbuster drug Ozempic.

When it reaches the intestine, the probiotic becomes a living drug. It remains “silent” when the blood glucose level is normal, but when it detects the level has risen above normal, it triggers the release of a hormone, GLP-1, to lower blood sugar. Ozempic and similar drugs prescribed to treat diabetes work by mimicking GLP-1.

Currently, diabetics must monitor their blood sugar level regularly and inject insulin or take oral medications to regulate it. There are 530 million diabetics worldwide today, a figure that could rise to 850 million by 2050, according to the International Diabetes Federation.

In monkeys, a single dose of the probiotic, which researchers named Gift (short for glucose-sensing and functional response probiotic), lowered blood glucose for up to three days. The next step is human trials. Production is being scaled up to satisfy US and European drug regulations. Lead scientist Ye Haifeng told China Science Daily in August the team hoped to have a health supplement based on Gift on the market “in about two years”.

Ye said the technology could be adapted to treat other metabolic diseases such as obesity and fatty liver disease.

In another breakthrough, scientists at Shandong University in Qingdao, eastern China, engineered Nissle 1917 to colonise tumours, where it becomes a drug factory, producing and delivering an anticancer medication, romidepsin. Because the drug delivery is highly targeted, the treatment doesn’t have the toxic side-effects of conventional chemotherapy.

The team showed the probiotic worked on mice with breast cancer, paving the way for targeted treatments for human cancers, but noted that the work was still in its early stages and had not yet been tested in humans.

Cancer researchers in Xiamen in southeast China, again using Nissle 1917, engineered what they described as a probiotic “microrobot” to penetrate a tumour, release an anticancer drug and become an “in situ vaccine” that stimulates the body’s immune system to attack the tumour.

At Henan province’s Zhengzhou University, researchers developed an oral alternative to expensive injectable medications to lower “bad” LDL cholesterol by engineering a probiotic to activate the same cholesterol-lowering protein as the drugs.

Probiotics found in cheese could alleviate symptoms of autism spectrum disorder (ASD), researchers from the Institute of Zoology at the Chinese Academy of Sciences found.

Mice bred to lack a gene critical for brain and gut development displayed traits of ASD, but after being administered the probiotics for a month their impaired curiosity towards new social environments was reversed and a crucial mechanism for learning and memory restored. While the probiotics they were fed targeted gut cells, their effects cascaded to the brain, the academy noted. The findings “open doors for innovative therapies”, it said. Fermentation has been used in traditional Chinese medicine for over 2,000 years to make it less toxic and improve its efficacy.

Recent studies have shown that fermenting TCM ingredients with probiotics not only makes them less toxic but promotes the full release of their active compounds while making them more therapeutic. For example, fermenting Chinese arrowroot with a probiotic increased the content of two of its active ingredients by 785 per cent and 1,010 per cent respectively, researchers at Taiwan’s China Medical University found.

Probiotic TCM fermentation can also produce new active ingredients. For example, fermenting Chinese yam with a probiotic produced a novel compound more digestible and with significantly better antioxidant properties than naturally occurring compounds in unfermented yam. The findings come from a study by researchers at Zhengzhou University, the State Key Laboratory of Food Nutrition and Safety and the Academy of Military Sciences.

Studies also show probiotic-fermented TCM is beneficial for general microbiome health. It regulates the patient’s immune system and promotes the growth of beneficial bacteria while suppressing that of toxic bacteria.

Thirty-five species or subspecies of microbes have been approved as edible probiotics in China, some of which have been used to ferment TCM ingredients. High-throughput screening – the automated laboratory testing and culturing of microbes – is being used to identify potential new probiotics for TCM fermentation. Chinese researchers have also proposed using synthetic biology to engineer more efficient probiotics for this purpose.

One procedure based on TCM principles that has drawn widespread interest among doctors and researchers is the use of healthy donor stools to treat a variety of conditions by restoring patients’ gut microbiomes to balance. The practice goes back 3,000 years.

A medical dictionary from China’s Western Zhou dynasty in the 10th century BC records the use of “golden juice” to treat infectious diseases, and another from the Eastern Jin dynasty 1,700 years ago has “yellow soup” being used to treat food poisoning and severe diarrhoea.

As their names suggest, these treatments were taken orally. Today faecal microbiota transplantation (FMT) is done via endoscopy, colonoscopy, enema or orally by swallowing capsules. Even so, patient acceptability and doctors’ concerns about patient dignity were big hurdles to its use, Yi-Chao Shi and Yun-Sheng Yang of the Institute of Digestive Diseases at the Chinese PLA General Hospital in Beijing noted in a 2018 medical journal paper.

Barriers may have been lowered since then. Today, clinical studies are under way in the country on the use of FMT to treat obesity and liver disease, combat sepsis, aid cancer treatment and alleviate major depressive disorder. Chinese researchers have already shown FMT can complement cancer therapies and improve the lives and communication skills of children with autism, the latter due to the beneficial effects of the gut-brain axis.

A focus of FMT research in China and elsewhere is its use to relieve intestinal illnesses. Prominent among these is infection (CDI), which causes diarrhoea and inflammation of the colon and can be life-threatening, and inflammatory bowel disease (IBD), a class of chronic disorders that often resist treatment and which are on the rise globally.

IBD is among the conditions which can be triggered by the breakdown of the body’s intestinal barrier that stops bacteria, toxins and other matter leaking from the intestines into the bloodstream.

Researchers at Nanjing Medical University led by Professor Faming Zhang developed the world’s first automatic system for isolating and purifying microbiota from donor stool and an improved method for administering FMT, which they described in a 2023 medical journal paper as “promising, safe and practical” and having high patient satisfaction.

They coined the term “washed microbiota transplantation” for FMT prepared and delivered this way, and published studies showing it reduced adverse events in IBD patients by some 80 per cent compared with manually prepared FMT.

Another pioneering FMT research team at Chinese University of Hong Kong has spent years developing the treatment for CDI, which can occur when patients are treated with some types of antibiotics. Elderly patients in hospitals and care homes are most at risk.

The university opened a stool bank and its Microbiota I-Centre developed a novel analytical platform, MOZAIC, that uses machine learning, over 800 FMT data sets and microbiome gene sequencing to match stool donors with recipients for better treatment outcomes and long-term safety.

Using the patented technology, the CUHK team, led by Professor Ng Siew-chien, achieved a treatment success rate of over 90 per cent in patients with recurrent CDI, and more than doubled patients’ median survival from 2.1 years to 4.7 years.

Researchers in China and elsewhere have begun combining FMT with engineered probiotics to treat IBD, with the former restoring a patient’s microbial community and the probiotics secreting anti-inflammatory drugs, suppressing molecules that trigger inflammation and restoring the intestinal barrier.

They are using also artificial intelligence (AI) to optimise the performance of the engineered probiotics. Algorithms can predict how a probiotic will interact with patients’ gut microbes and use simulations to find the strains best able to restore balance to their microbiome. AI can also drive the editing of probiotic genes to improve their targeting, as outlined in a study by researchers at Zhejiang Lab in Hangzhou, eastern China. The end goal is personalised IBD treatment with customised therapies.