Research dietitian Jane Varney at Monash University in Melbourne, Australia, and co-workers will use their Global Grant for Gut Health to examine whether adding fermentable fibre to food could help reduce the symptoms and impact of long COVID.
Metabolites produced by microbes in the gut (pictured) feeding on fermentable fibre may influence long COVID.Credit: THOM LEACH/Science Photo Library/Getty
What inspired your project proposal?
Affecting around one in ten people infected with SARS-CoV-2, long COVID is a significant global health challenge. It causes a range of debilitating symptoms, including fatigue, brain fog and problems with the immune system. However, we know very little about the condition and what causes it, and there are no standard treatments. Long COVID is already placing a considerable burden on healthcare services around the world, and this situation will only escalate as COVID variants continue to spread.
We will examine a non-drug, dietary supplement option based on fermentable fibre, which we believe may relieve symptoms and improve quality of life. Such dietary interventions may also help boost people’s immune systems and provide protection from future COVID-19 infections.
What are the main objectives of your project?
We have two objectives. First, we will examine whether adding two forms of fermentable fibre to baked goods alleviates long-COVID symptoms compared to a placebo diet. Since long COVID has a myriad of symptoms, it’s important to select specific symptoms to track in this study. And so we will recruit patients suffering specifically from brain fog and fatigue.
Second, we hope to determine how fermentable fibre modulates the metabolites produced by different gut-microbe species and how the body’s immune system responds to those metabolites. I will be working closely with immunologist Paul Gill, also at Monash University, who has a strong interest in how diet affects the immune system. In his PhD project, he investigated the value of adding fermentable fibre to the diet of healthy people and found that this boosted their immune systems. This provided the preliminary human data that supported our GGGH project. We are also grateful for the support and expertise of the rest of our team, including our colleagues with specialist knowledge of long COVID and the hospital staff through whom we will reach potential participants.
Why choose fermentable fibre?
Previous studies found that fermentable fibre helps modulate immune responses and contributes to the overall health of the gut microbiome. Gut microbiota feed on fermentable fibre as a key fuel source. The two fibre types we will use are inulin and resistant starch (starch that isn’t digested in the small intestine), which are easily fermented in the gut. The byproducts — or metabolites — generated by this fermentation include short-chain fatty acids such as butyrate.
Previous studies have shown that patients with chronic fatigue syndrome, which has similar symptoms to long COVID, have reduced levels of short-chain fatty acids and suffer from an imbalanced gut microbiota. We also know from animal studies that supplementing the diet with fermentable fibre boosts the production of butyrate and other short-chain fatty acids, and that these metabolites then act on immune cells to ameliorate symptoms of SARS-CoV-2 infection.
We plan to give people suffering from long COVID a fermentable-fibre intervention to explore whether these same effects occur. We will analyse how the immune cells of each participant respond to the boost in short-chain fatty acids, and we will also ask patients to track their long COVID symptoms over three weeks.
Can a change in diet for three weeks make a difference?
Gill’s previous work showed that a similar fermentable-fibre intervention of this duration and size was well tolerated and was sufficient to modulate immune cells and gastrointestinal symptoms in healthy people. The three-week intervention strikes a balance between optimal trial design and feasibility in terms of patient compliance — people don’t like being told what to eat for too long! We will also optimize compliance by allowing participants to consume their usual diet and only add two intervention items per day. We have a chef who will create tasty snack bars and muffins containing higher levels of inulin and resistant starch. To avoid unpleasant gastrointestinal side effects, we will ask participants to space out the fibre intervention over each day, rather than consuming all the fibre in one sitting. Half of the cohort will be given placebo foods (containing rice flour instead of fermentable fibre), and we will track all participants’ responses to the dietary interventions through stool and blood samples, together with tracking their long-COVID symptoms.
What do you hope to find?
Because we are examining a potential gut–brain association, we hope that collecting stool samples will give us insights into changes in the function and composition of the gut microbiota and how these relate to changes in long COVID symptoms. We will monitor the different species of bacteria that are involved in producing short-chain fatty acids and have been previously identified as being at low abundance in people with long COVID. We also want to pinpoint exactly which bacterial species in the gut are influenced by increased fibre intake, and how their metabolic output changes. Recent advances in screening technologies mean we can examine the intricate details of the interactions between dietary inputs, gut microbes and immune cells. We will screen stool samples for microbial DNA and metabolites, while blood samples will provide us with data on immune-cell types and levels of inflammatory cytokines in plasma.
All these data will be collected and compared in intervention and placebo groups before, during and after the dietary intervention. We’re hoping that there might be some subtle immune cell changes in response to diet we can detect, which may not necessarily be seen with a more general look at the immune system during long COVID. We’d also like to pinpoint microbial and immune-system signatures associated with symptom severity.
What plans do you have for future research?
If we see positive effects from this specific dietary intervention, we would like to confirm them in a larger trial. If the intervention is effective, it could provide patients with a low-cost, non-drug option for managing long-COVID symptoms.
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