Bugs as drugs – medicine’s next frontier

Microbiome research is providing tantalising clues about how we might change our microbiota to improve our health. But translating findings from the lab into clinical treatments is a slow and arduous process.

The most dramatic illustration of how our microbiota can be used in the clinic is the case of the poo transplant, also known as faecal microbiota transplantation.

In poo transplants, the recipient’s bowel microflora is replaced with a sample of microbes – along with some intestinal cells and the metabolite-rich broth they live in – from a healthy person’s gut.

Over the past five years, the technique has become a standard treatment for people suffering repeated bouts of a severe – and deadly – diarrhoea caused by Clostridium difficile.

A small number of people naturally harbour C. difficile in their large intestine. But most pick it up in hospitals or nursing homes and succumb to its wrath after a course of antibiotics disrupts their usual gut microflora.

Poo transplants to treat recurrent C. difficile infection have success rates upwards of 90%, far surpassing antibiotic efficacy. “It’s pretty remarkable,” says Vincent B Young, an infectious diseases physician from the University of Michigan in the US who studies faecal transplants.

This has prompted many to see poo transplants as the answer to myriad other conditions linked to changed gut communities. “And that’s getting a little bit iffy,” Young says.

“I think that [faecal transplants] as a therapy is sort of a stop-gap as we try to learn more and come up with better ways to manipulate the microbiome.”

This hasn’t stopped online communities exchanging information about how to perform DIY poo transplants for conditions ranging from inflammatory bowel disease to autism to multiple sclerosis.

Young sees this is risky business. People could unwittingly transfer pathogens or replace one out-of-balance ecosystem for another, such as in the case of the UK woman who became obese following a poo transplant from her overweight daughter.

A better approach would be to deliver tailored probiotics containing only specific species of bacteria required to treat a particular disease or individual. “It would be great if we could examine someone’s microbiota, get a sample of faeces and say, ‘oh, you’re missing this, this, this and this,’ and [then we can] replace that,” says Young.

Individualised probiotic therapy is a long way off. But several companies are already investing in probiotic therapies on the back of microbiome research. While probiotics have been a mainstay of the health food and nutritional supplement industry for decades, modern probiotics are being shunted through the rigours of clinical trials in the same way as conventional drugs.

The trend is towards well-defined concoctions that contain one or more microbial species. Even for C. difficile infection, where faecal transplants have been so successful, companies such as Seres Therapeutics in Boston, US, are developing oral capsules containing key components of the gut ecosystem as a more palatable treatment option.

Others are packaging select species that play a protective role in the gut. Vedanta Biosciences, for instance, also based in Boston, is gearing up to test a probiotic cocktail of beneficial ‘clostridial cluster’ microbes on people with inflammatory bowel disease.

California’s Osel, meanwhile, is developing single-species products. One contains the vaginal ‘good guy’ Lactobacillus crispatus to treat women who get repeated urinary tract infections and bacterial vaginosis, which is caused by disturbances to the vaginal microbiota.

Another is to treat C. difficile infection and inflammatory bowel disease. It contains Clostridium butyricum, a microbe that produces the short-chain fatty acid butyrate and has been shown to quell bowel inflammation in mice.

There is also ongoing research into probiotics we can already find on our supermarket shelves. Lactobacillus and Bifidobacterium species are the most common.

A scientific review of their effects found that whether or not the probiotic works depends on what condition is being treated and the specific strain of bacteria used. Although they are widely recognised as supporting a healthy gut ecosystem, not all over-the-counter probiotics will deliver desired health benefits.

Still others look at tinkering with our microbial multitudes by feeding them supplements – called prebiotics – or drugging them.

The most commonly pursued prebiotics are fermentable fibres, such as inulin and short chain sugars bacteria use as food. These promote the growth of particular species that produce short chain fatty acids, which help to maintain a healthy gut lining.

Drugging the microbiome is a relatively new frontier. Several companies are on the search for drugs that could alter microbial metabolism, or interfere with the cross-talk between microbes and us. As we continue to untangle the web of interactions between our microbes and ourselves, these approaches could become more common.

Most microbiota therapies won’t find their way onto our doctors’ prescription pads any time soon. But it is clear that the medical profession – and pharmaceutical companies – are realising that looking after our microbes is a crucial part of looking after ourselves.