Don’t drink up if there are sugar-laden soft drinks in your glass or in the plastic bottle you just bought. Their consumption, supplemented with white sugar, alters the DNA of gut bacteria and affects the host’s immune system. Plain tap water is much better.

But there is some good news from researchers at Haifa’s Technion-Israel Institute of Technology: Such effects are reversible.

The team from the Technion’s Ruth and Bruce Rappaport Faculty of Medicine was led by Prof. Naama Geva-Zatorsky, doctoral student Noa Gal-Mandelbaum, Dr. Tamar Ziv, and the Smoler Proteomics Center and was just published in the prestigious journal Nature Communications. Their research, titled “Dietary carbohydrates alter immune-modulatory functionalities and DNA inversions in Bacteroides thetaiotaomicron,” was conducted on lab mice.

They explained that bacteria in the gastrointestinal system – the long tube from the stomach to the anus that breaks down food, absorbs nutrients, and excretes waste – are vital members of the microbial community within our body, which is known to scientists as the microbiome. These bacteria, which have co-evolved with humans for generations, are as varied as a zoo and so essential to human health, in general, and to the development of the immune system, in particular, that we can’t function without them.

The gut bacteria environment is highly dynamic, and the conditions there were shown to affect microbial composition. Yet, their influences on bacterial functionality – immune-modulation activity – are mostly overlooked. Strains of the same bacterial species can regulate the immune system in distinct ways, sometimes with contradicting reactions (anti- and pro-inflammatory effects), so studying the functionality of strains under different conditions is crucial, they explained.

NOA GAL-MANDELBAUM.
NOA GAL-MANDELBAUM. (credit: TECHNION)

The team analyzed functional changes in the gut symbiont called Bacteroides thetaiotaomicron (B. theta) under different dietary components consumption in humans, upon white sugar consumption in mice, and in response to 190 different carbon sources in vitro.

A symbiont is a bacterium or fungus that lives in the gut of a host organism that benefits the host through a mutually beneficial symbiotic relationship. B. theta helps prevent inflammation of the gut, preserving its mucus layer and protecting the host from invasion by a pathogen.

These microorganisms contribute to digestion by providing essential nutrients, protect against pathogens and parasites, help with immunity, and can even detoxify harmful compounds.

Thus, they affect the physiology and overall health of the animal or human in which they live, said Geva-Zatorsky, who studied biology and chemistry at Tel Aviv University, went on to systems biology for her master’s degree and doctorate at the Weizmann Institute of Science in Rehovot, and did her postdoctoral work in microbiology and immunology at Harvard University in Boston.

CHANGES IN diet affected the orientation of phase variable regions in B. theta in humans, in vivo, and in vitro and changed B. theta’s proteome and immune-modulatory functionality. In vivo research takes place within a whole, living organism such as an animal or human; in vitro research is conducted outside of a living organism in a controlled laboratory setting, such as a test tube or petri dish. The researchers studied the effects of consuming different dietary components on the DNA profile of these bacteria in all three locations.

The proteome is the whole collection of proteins within a cell, tissue, or organism at a given time, and it can change depending on cell type and conditions. Immune-modulatory functionality refers to a cell or substance’s ability to change, enhance, or dampen to get a host immune response and achieve a desired outcome, like preventing an autoimmune reaction or fighting an infection.

Geva-Zatorsky told The Jerusalem Post, “Our study first focused on analyzing data on humans; this data unfortunately did not include honey, but it did include artificial sweeteners in diet soft drinks, yet the signal there was not significant.”

She continued that the researchers “identified a strong signal of bacteria responding to sugar, apparent in non-diet soft drinks and sugary tea and coffee. Since the common ingredient between these is white sugar, we then studied the effect of white sugar on the bacteria directly when they were colonizing mice by giving them sugar water to drink. We found the same effect on the bacteria, both from humans and from mice, in which we showed the consequences on the immune system – inflammation.”

Gut bacteria must adapt to constant changes in environment

The human gut is constantly influenced by changes in the environment, they concluded. “To keep up, our gut bacteria must adapt quickly. They do this through a process called functional plasticity that enables them to change their functions and behavior in response to factors such as nearby microbes, what we eat, and the status of our health.”

A previous study by the team discovered that one way gut bacteria adapt to environmental changes is through DNA inversions – speedy genetic switches that help them respond and defend themselves.

In their study, the researchers investigated how these DNA inversions occur in response to dietary factors. They found that consuming soft drinks containing white sugar can change the gut bacteria’s DNA and, in turn, impact the host’s immune system.

They discovered that white sugar consumption causes DNA inversions in these bacteria, which led to changes in inflammatory markers of the immune system, including those in T-cell populations, cytokine secretion, and gut permeability.

The good news is that once mice stopped consuming white sugar, the state of bacterial DNA inversion and the immune system returned to normal. They said their study stresses the importance of understanding the complex effects of nutrition on the microbiome and our health.

“Studying the effects of dietary components on the functionalities of key members of the gut microbiota will make possible the customization of dietary recommendations to individuals,” the Technion researchers concluded.

“We believe that this will make [it] possible [to] tailor dietary recommendations to people to improve their immune system’s state and their health in general.”