Why poor health could be a gut feeling

SCIENTISTS have long known the human digestive tract is important, but it's only in the past 15 years that they've had a different perspective on the countless microbes it hosts. Could they be related to diseases beyond the digestive system?

Trillions of microorganisms live in your body: bacteria, viruses and fungi that are collectively referred to as the microbiome. Each organ or system has its own microbiome, including the skin, the mouth and the genitals, and these days each one is studied individually.

Experts believe diabetes, asthma, allergies, liver diseases, certain psychiatric disorders and brain conditions, cancer, autoimmune diseases, obesity, heart complaints and others might be linked to the microbiome.

The area of greatest focus is the microbiome of the digestive tract, as most microorganisms are found there: those that are beneficial or harmful to us, and those that are neutral.

Prof Stephen O’Keefe, director of the African Microbiome Institute at Stellenbosch University, says until recently scientists thought only a few species of microorganisms lived in the digestive system. “Now we know there are thousands. It is one of the most essential parts of our lives because it can alter what happens in the body," he says from Pittsburgh in the US, where he spends half the year.

“It starts with your mouth and oesophagus, then the small intestine, and then in your large intestine there's a dramatic increase in microorganisms."

Bacteria thrive on nutrients the body can't necessarily absorb, specifically fibre that ferments in the colon. Without this food they can't survive, which is why a no- or low-fibre diet — often one that contains a lot of fast food and refined foods — is bad for you.

The bacteria metabolise the fibre and produce short-chain fatty acids, explains O'Keefe. These are important for maintaining the mucous membrane lining the digestive system. When it gets damaged, you get a “leaky gut". This causes undigested food and toxic waste products to enter the bloodstream. Some experts refer to this as dysbiosis.

The story is bigger than just antibiotics and other medication that can destroy the good bacteria in your digestive system. Researchers are also studying whether dysbiosis can affect the brain. 

Faeces by courier

Prof Sian Hemmings, a molecular biologist affiliated with the psychiatry department at Stellenbosch University, is the lead researcher of the South African Microbiome Initiative in Neurosciences (saNeuroGut). It  recently called on people to contribute DNA (a saliva swab) and a small amount of faeces to a research project that aims to correlate gut microbial compositions to health, cognitive and psychiatric data. A courier will collect the samples from your home after you've registered.

Hemmings explains that it's only in the past decade that scientists have begun to unravel how bacteria in the digestive system influence the brain through the enteric nervous system, which has millions of nerves lining the gut. The system allows interaction between the digestive system, bacteria and the central nervous system.

Your brain can also affect your digestive system, says Hemmings, especially if you have anxiety, stress or depression. This is because you then secrete cortisol, and it changes the microbial environment in your intestines. “We're learning this all the time and still trying to unravel the mechanisms."

There are three ways the digestive system can affect the brain: a leak; production of serotonin by bacteria; and production of metabolites that enter the bloodstream.

A leaky digestive system releases bacteria into the bloodstream. This causes a systemic inflammatory response, and a neuroinflammatory response if it reaches the brain. Research in “germ-free mice" suggests   some of the most severe psychiatric illnesses and conditions may be linked to what's happening in your intestines.

The pilot study at saNeuroGut aims to see if there's a difference in the microbial composition of people who have anxiety, stress, depression or post-traumatic stress, compared to other people. They can't make a diagnosis, but DNA analysis reveals the interaction between the genome and bacteria, informing further research.

Dr Ovokeraye Oduaran, of the Sydney Brenner Institute for Molecular Bioscience at Wits University, says people acquire their microbiome — or most of it — during the birthing process, especially with a natural birth where the baby passes through the vaginal canal. After that, you receive a lot of what you need from breast milk.

O'Keefe says those initial exposures play a key role for the rest of your life. They are also linked to the development of allergies and asthma, especially if you're not exposed to a variety of environments.

Oduaran says research shows a significant difference in the microbiomes of Africans from cities and those in rural areas. “When people no longer cook at home, it changes. That's why there's a movement towards becoming vegetarian, towards a plant-based diet, because it nourishes your bacteria." Researchers are also studying the role the microbiome could play in obesity, mostly in non-communicable diseases.

Asking people to donate faeces for research is a challenging task, says Oduaran. “But I'm crazy about my job! We use DNA analysis and don't peer through a microscope at, you know, bits in a dish," she laughs.

Probiotics or faecal transplants?

It's still a long road before there's truly effective treatment, says Hemmings. She mentions that although she doesn't work with probiotics such as kefir, which is milky and contains live bacteria, they can be beneficial. However, they have to be consumed daily to make a difference. “My opinion is [that you need] to eat right," says O'Keefe.

A study he conducted looked at how the digestive system's mucous membrane can change in just two weeks when people switch to a fibre-rich diet. Scientists observed this by performing colonoscopies before and after the period, discovering that the inflammation process was halted. A plant-rich diet is simply better, says O'Keefe, pointing out that populations who consume a lot of meat and fat and little other food have some of the highest rates of colon cancer.

People who become critically ill from Clostridium difficile — due to the use of antibiotics or after a long hospital stay — can take months to recover. Some have almost untreatable diarrhoea because their microbiome has been so disrupted, and as many as a third of them can die without treatment.

Faecal microbiota transplantation involves healthy individuals donating faeces which are then transferred to the patient. It's not as unpleasant as it sounds. Donations are processed in a sterile medical environment then transferred during a colonoscopy or through a nasogastric tube.

In a study four years ago by the Wits Donald Gordon Medical Centre in Johannesburg, involving women over 65, this treatment was highly successful and all 27 subjects survived the illness. 

Another 2019 clinical trial involved three people whose skin cancer had spread to other parts of the body. As well as conventional drugs, they received faecal transplants. The research on this, published in the journal Science, focuses on cancer drugs that block a protein (PD-1) found on the surface of immune cells (T-cells). For some people, these drugs work wonders and put them in remission for years.

Experiments in mice with tumours showed that they fared better when they received faecal transplants as well as the drugs. In the human trial, the microbiome of the three subjects become similar to that of the donors, and two of them saw their tumors shrink. Their immune response could be altered.

It might be a small beginning, but the human microbiome and its bustling organisms might still unlock new treatments and answers to nagging questions about what makes people sick or sicker.

♦ VWB ♦

BE PART OF THE CONVERSATION: Go to the bottom of this page to share your opinion. We look forward to hearing from you!