She explores the deep sea of the gut

Around half of all deaths from cardiovascular and metabolic diseases can be linked to diet. Research shows a connection between dietary fibre intake and the risk of developing these diseases, which at first glance seems puzzling.

Humans cannot break down or absorb fibre directly. Instead, it nourishes billions of bacteria that primarily colonise our large intestine. 

“When gut bacteria break down fibre, they produce short-chain fatty acids. These compounds are beneficial to us, but they act mostly locally and are barely detectable in the bloodstream. So, the question is why there is such a strong link between fibre and cardiometabolic diseases,” says Karolina Sjöberg Jabbar, physician and researcher at the Wallenberg Laboratory for Cardiovascular and Metabolic Research.

Can break down mucus

She believes the problem arises from what the bacteria in the large intestine do when they lack access to fibre. Her theory is that they begin to break down the thin layer of mucus that coats our intestines.

“The intestinal lining consists of a single layer of cells, which makes it vulnerable. There’s a significant risk that interactions between bacteria and immune cells can go wrong and trigger inflammation. The reason this doesn’t happen more often is precisely because we have this extra layer of protection in the form of mucus,” she explains.

When mucus is broken down, it can also release bacteriophages – a type of virus. These transfer genetic material between bacteria and can either benefit or harm them.

“Phages are tiny, much smaller than bacteria. My theory is that when phages are released, they can easily cross the intestinal lining and trigger a local immune response, but also spread through the bloodstream,” she says. 

The breakdown of mucus by bacteria can also generate various metabolites, which are a type of by-product. These too may be harmful, but more research is needed to understand how these processes work. 

“We still know very little about mucus-dwelling bacteria, and especially phages. They’re a bit like dark matter in medical research—we don’t even have a way to classify them,” she says.

Important messengers 

She completed her postdoctoral fellowship at the Broad Institute in the United States, a leading biomedical research centre jointly run by Harvard and Massachusetts Institute of Technology (MIT). Among other things, she studied the microbiota of mothers and infants and discovered that certain bacteria in the mother influenced the infant’s gut flora – even though those bacteria weren’t present in the child.

The explanation lay in the role of phages as messengers – a discovery published in the prestigious journal Cell. Many bacteria are temporarily transferred from mother to child during birth, but since the infant’s gut environment is entirely different, they cannot establish. When these bacteria become stressed and are essentially dying, they release their phages.

“The phages transfer certain functions to other bacterial strains in the infant, especially genes that govern the ability to break down breast milk. So, phages play a crucial role in shaping the infant’s gut flora and the development of the immune system,” she says.

Discovered bacteria linked to IBS

Karolina Sjöberg Jabbar’s interest in research was sparked during her residency at Sahlgrenska University Hospital, where she became involved in a study on pancreatic cancer. It’s a silent form of cancer with vague symptoms and a poor prognosis.

During her PhD studies, she developed a new method to detect precursors to pancreatic cancer. She also studied the composition of mucus in the gut. Her supervisor was Gunnar C. Hansson, professor at Sahlgrenska Academy and a world-leading pioneer in the field. 

“Mucus is like the deep sea – we know very little about what moves within it, even though we secrete several litres of mucus every day, just in the gut. It’s a challenging area to study. Mucus is transparent and dries almost instantly, so you need a method to keep the biopsy alive and visualise its surface,” she says.

It was by analysing the gut’s mucus and its protein composition that Karolina Sjöberg Jabbar and her colleagues made an intriguing discovery in 2020. They were able to link the presence of the bacterium Brachyspira in the intestinal mucosa to IBS – a finding that could eventually pave the way for new treatments. 

New expertise during the pandemic

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Karolina Sjöberg Jabbar has successfully established herself as an independent researcher. She now leads her own research group and was appointed group leader at the Wallenberg Centre for Molecular and Translational Medicine last year. 

If she could offer advice to her younger self as a researcher, it would be to worry less about making her thesis perfect, to invest more in networking, and to build stronger skills in data analysis.

The COVID-19 pandemic struck shortly after she moved to the United States for her postdoc. Instead of working in the lab, she had to learn bioinformatics remotely and joined a data analysis team.

“It was completely new to me and a real challenge, especially with two children at home full-time. But I’m incredibly grateful for it now. It gave me new expertise and broadened my perspective as a researcher. For me, data analysis is the most exciting part – when you suddenly get an idea or spot a connection,” she says.

What Karolina Sjöberg Jabbar’s next discovery will be remains to be seen. Her long-term goal is to find a way to strengthen the gut’s mucus layer.

“Advising patients to eat more fibre is the simplest thing for a doctor to do – but it places the entire burden on the patient. Changing one’s lifestyle is incredibly difficult. If we could find a way to reinforce the gut’s mucosal defences, we could offer a completely new form of targeted prevention against cardiovascular disease,” she says.

TEXT AND PHOTO: KARIN ALLANDER