Helping Beneficial Bacteria Survive in the Human Gut


Scientists at Yale report that they have uncovered a novel mechanism by which “good” bacteria colonize the gut. The microbes that inhabit the gut are critical for human health, and understanding the factors that encourage the growth of beneficial bacterial species in the gut may enable medical interventions that promote gut and overall human health.

Specifically, the Yale team discovered that one of the most abundant beneficial species found in the human gut showed an increase in colonization potential when experiencing carbon limitation—a finding that could yield novel clinical interventions to support a healthy gut.

The study “Bacteria require phase separation for fitness in the mammalian gut” appears in Science.

“Therapeutic manipulation of the gut microbiota holds great potential for human health. The mechanisms bacteria use to colonize the gut therefore present valuable targets for clinical intervention. We now report that bacteria use phase separation to enhance fitness in the mammalian gut,” write the investigators.

“We establish that the intrinsically disordered region (IDR) of the broadly and highly conserved transcription termination factor Rho is necessary and sufficient for phase separation in vivo and in vitro in the human commensal Bacteroides thetaiotaomicron. Phase separation increases transcription termination by Rho in an IDR-dependent manner. Moreover, the IDR is critical for gene regulation in the gut. Our findings expose phase separation as vital for host-commensal bacteria interactions and relevant for novel clinical applications.”

The Yale team, based in the lab of geneticist Eduardo Groisman, the Waldemar Von Zedtwitz, PhD, professor of microbial pathogenesis, found that the beneficial gut bacterium Bacteroides thetaiotaomicron responded to starvation for carbon by sequestering a portion of the molecules for an essential transcription factor within a membrane-less compartment.

Important role for a transcription factor

The team established that sequestration of the transcription factor increased its activity, which modified the expression of hundreds of bacterial genes, including several that promote gut colonization and control central metabolic pathways in the bacterium. These findings reveal that “good” bacteria use sequestration of molecules into membrane-less compartments as a vital strategy to colonize the mammalian gut.

Bacteroides thetaiotaomicron and other bacteria residing in the mammalian gut have access to nutrients ingested by the host animal. However, there are also long periods of time when the host organism does not eat. Deprivation of nutrients, including carbon, elicits the production of colonization factors in beneficial gut bacteria, the researchers found.

“One of the things that emerged is that when an organism is starved for carbon, that is the signal that helps produce properties that are good for surviving in the gut,” said Aimilia Krypotou, PhD, a postdoctoral fellow in Groisman’s lab and lead author of the study.

The findings could help spur the development of new probiotic therapies for gut health, noted Krypotou, adding that “most studies just look at abundance of bacterium. If we don’t understand what’s happening at the molecular level, we don’t know if it would help.”

Scientists Warn: Food Coloring Nanoparticles May Damage Human Gut


Chicken Intestine Food Nanoparticles

Cross-section of chicken intestine with cells that may be affected by food nanoparticles.

According to a recent study by scientists at Cornell and Binghamton University, metal oxide nanoparticles which are frequently utilized as food coloring and anti-caking agents in the food industry, may cause damage to certain sections of the human intestine.

“We found that specific nanoparticles – titanium dioxide and silicon dioxide – ordinarily used in food may negatively affect intestinal functionality,” said senior author Elad Tako, associate professor of food science at Cornell. “They have a negative effect on key digestive and absorptive proteins.”

In their study, the research team administered human-equivalent doses of titanium dioxide and silicon dioxide in the Tako laboratory’s in vivo system, which provides a health response that closely resembles that of the human body.

The scientists injected the nanoparticles into chicken eggs. After the chickens hatched, the scientists detected changes in the functional, morphological, and microbial biomarkers in the blood, the duodenum (upper intestine), and the cecum (a pouch connected to the intestine).

“We are consuming these nanoparticles on a daily basis,” said Tako. “We don’t really know how much we consume; we don’t really know the long-term effects of this consumption. Here, we were able to demonstrate some of these effects, which is a key to understanding gastrointestinal health and development.”

Despite the finding, the scientists are not yet calling for an end to the use of these nanoparticles.

“Based on the information, we suggest simply being aware,” Tako said. “Science needs to conduct further investigations based on our findings. We are opening the door for discussion.”

Reference: “Food-Grade Metal Oxide Nanoparticles Exposure Alters Intestinal Microbial Populations, Brush Border Membrane Functionality and Morphology, In Vivo (Gallus gallus)” by Jacquelyn Cheng, Nikolai Kolba, Alba García-Rodríguez, Cláudia N. H. Marques, Gretchen J. Mahler and Elad Tako, 9 February 2023, Antioxidants.
DOI: 10.3390/antiox12020431

The study was funded by the National Institutes of Health.

Nanoparticles are used in food colorings to improve their stability, solubility, and color intensity. Food coloring nanoparticles are made by reducing the size of color particles to the nanoscale range, typically between 1 and 100 nanometers in diameter.

Nanoparticles have a larger surface area than larger particles, which makes them more reactive and improves their ability to disperse in food. This improved dispersion leads to better color stability, as the nanoparticles are less likely to clump together or settle out of the food product.

In addition to stability, nanoparticles can also enhance the intensity of food colors. This is because the smaller size of the particles allows them to interact more efficiently with light, resulting in more vivid and intense colors.

However, it is important to note that the use of nanoparticles in food has raised concerns about their potential health effects. As a result, regulatory bodies such as the U.S. Food and Drug Administration (FDA) require that food manufacturers provide evidence that the nanoparticles they use are safe for consumption.

‘New virus’ discovered in human gut


Scientists have discovered a previously unknown virus living in the human gut, according to a study in Nature Communications.

Exploring genetic material found in intestinal samples, the international team uncovered the CrAssphage virus.

They say the virus could influence the behaviour of some of the most common bacteria in our gut.

Experts say these types of viruses, called bacteriophages, have been shown to play a role in chronic diseases.

Electron micrograph scan of viral DNA

“Start Quote

The fact it has flown under the radar for so long is very strange”

Prof Robert Edwards San Diego State University

Led by a team at San Diego State University in the USA, scientists scoured genetic information stored in three large international databases.

They stumbled upon a piece of DNA, some 100,000 letters long, present in more than half of all samples from the gut.

‘Novel virus’

And while cross-checking its identity in global directories they realised it had never been described before.

Prof Robert Edwards, lead author, said: “It is not unusual to go looking for a novel virus and find one.

“But it’s very unusual to find one that so many people have in common.

“The fact it has flown under the radar for so long is very strange.”

Researchers say the virus has the genetic fingerprint of a bacteriophage – a type of virus known to infect bacteria.

Phages may work to control the behaviour of bacteria they infect – some make it easier for bacteria to inhabit in their environments while others allow bacteria to become more potent.

Dr Edwards said: “In some way phages are like wolves in the wild, surrounded by hares and deer.

“They are critical components of our gut ecosystems, helping control the growth of bacterial populations and allowing a diversity of species.”

According to the team, CrAssphage infects one of the most common types of bacteria in our guts.

‘Powerful tools’

They are now trying to grow the virus in a laboratory. And they say the next step would be to work out exactly how the virus affects our gut bacteria.

Dr Martha Clokie, at the University of Leicester, who was not involved in the research, told the BBC: “What is exciting here is the scientists have produced new techniques and powerful tools to help identify previously unknown viruses.

“And thinking longer term, we know bacteria can play an important role in chronic diseases such as obesity and diabetes.

“If we can pin down these viral controllers, we could perhaps one day use them to modify any harmful bacteria, rendering them less powerful.”