Researchers discover how rare protist blastocystis ST7 causes gut disease

The human gastrointestinal system, also known as the gut, serves as a complex ecosystem where food is transformed into vital nutrients for the body. Within this system, a diverse array of microorganisms thrives, including thousands of bacterial species. While some of these microbes can be harmful, many play a crucial role in maintaining human health. Apart from bacteria, the gut microbiota encompasses other microorganisms like protists, yeasts, and viruses.

Among these microorganisms, Blastocystis, the most common protist globally, exists in various subtypes. Depending on the subtype (ST) present in an individual, it can either contribute to a healthy gut or lead to gastrointestinal issues.

In Singapore, a less common subtype called Blastocystis ST7 is frequently associated with diarrhea in patients. Notably, this subtype is more prevalent in Asia than in Western regions. These observations, along with supporting research, suggest that Blastocystis ST7 may be a causative factor in gut diseases, although the exact mechanisms have remained elusive.

To unravel how Blastocystis ST7 triggers gut disease, a team of researchers led by Professor Nicholas Gascoigne from the Department of Microbiology and Immunology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), and Associate Professor Kevin Tan embarked on a molecular-level investigation. Their findings have been published in The EMBO Journal.

The study, led by Dr. Lukasz Wojciech, Senior Research Fellow at NUS Medicine’s Department of Microbiology and Immunology, unveiled the role of Blastocystis ST7 in gut disease. This subtype produces a substance known as indole-3-acetyldehyde (I3AA) during its metabolic processes.

“I3AA is a rare metabolite, produced by very few organisms. It binds to immune cells within the gut, reducing the gut’s tolerance for beneficial gut bacteria. This leads to an overactive immune response even in the presence of normal gut bacteria. Additionally, I3AA fosters gut inflammation by inhibiting the protective functions of a vital group of immune cells called regulatory T cells, while simultaneously promoting inflammation through another type of immune cell known as T helper 17 cells,” explained Dr. Wojciech.

A/Prof Tan noted, “Biologically, this is the first time that the rare metabolite I3AA has been extensively studied and demonstrated to promote inflammation.”

The researchers also identified certain bacteria, such as lactobacillus, commonly found in foods like yogurt, cottage cheese, and sourdough bread, as effective in counteracting the effects of I3AA in the gut. Lactobacillus is known for its ability to regulate immunity and assist in gastrointestinal health. Therefore, one potential approach to treating Blastocystis ST7-associated diarrhea could involve incorporating lactobacillus-rich foods into one’s diet.

“Based on our discoveries, it’s crucial to pinpoint the specific Blastocystis subtypes linked to diseases, as some subtypes are harmful while others are not. This could lead to more precise diagnoses and treatments for patients. Our team is currently conducting further studies in this regard. We aim to determine if I3AA production is unique to ST7 and whether it can serve as a disease biomarker. Additionally, we’re exploring whether certain strains of lactobacilli can counteract the inflammatory effects of Blastocystis ST7 on the host,” stated Prof Gascoigne.

Source: National University of Singapore

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