Tag: mucus

Antibiotic Usage can Damage the Intestine’s Protective Mucus Layer

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Researchers at Umeå University and Tartu University have found that a history of repeated antibiotic use causes defects in the normally protective mucus barrier of the gut, due to antibiotic-driven alterations in the microbiota. In a further study in a different collaboration, the researchers found a bacteria-independent mechanism through which antibiotics can damage the mucus barrier directly.

The results have been published in the scientific journals Gut Microbes and Science Advances.

“Together, these two studies suggest that antibiotics can damage the mucus layer through at least two independent mechanisms, and that they may have long-lasting effects through an altered gut bacteria. This further supports the notion that antibiotics should be administered in a responsible manner,” says Björn Schröder, Docent in Infection Biology in the Department of Molecular Biology at Umeå University.

Previous research has shown the consequences of short-term antibiotic treatments on the intestinal environment, but it is less clear how repeated antibiotic use in past years can affect our guts.

To address this question, Björn Schröder and his group at Umeå University teamed up with a research group at Tartu University in Estonia, who have built a deeply characterised cohort of individuals that provided stool samples and health records.

The researchers selected individuals who had taken at least five courses of antibiotics in the past, but not within six months before the stool collection, and compared their microbiota composition to individuals who had not taken any antibiotics within the last 10 years.

“The analysis revealed changes to the gut bacteria composition, even though the antibiotics were taken a long time ago. These results indicate that repeated antibiotic use has a lasting effect on gut bacteria composition that can persist at least months after the last treatment,” says Kertu-Liis Krigul, PhD student at Tartu University.

After transplantation of the human microbiota into mice and using specialised methods to analyse the mucus function in the gut, the researchers found that the function of the mucus layer was disrupted in mice transplanted with bacteria from humans with a history of repeated antibiotic use. Expansion of the mucus was reduced, and the mucus layer became penetrable, allowing bacteria to move closer to the intestinal lining.

“Looking at the bacteria present in the gut in more detail, we could see that bacteria known to feed on the mucus layer were present at higher levels in these mice. This further supports a role for the gut bacteria in determining how well the mucus barrier can function,” says Rachel Feeney, PhD student at the Department of Molecular Biology at Umeå University.

A separate study carried out in another international collaboration, further showed that antibiotics can also directly disrupt the mucus barrier in a gut bacteria-independent manner.

By giving the antibiotic vancomycin to normal and ‘bacteria-free’ mice, the researchers were able to show that this antibiotic can act directly on the mucus barrier, independent of the gut bacteria. Complementary experiments on intestinal tissue were carried out at Umeå University and showed that the antibiotic could disrupt the mucus expansion within a few minutes of application.

Source: Umeå University

Mucus is Snot a Problem for Bacteria, Which Swarm Through It

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The increase in mucus from sniffles and runny noses is exactly what bacteria use to mount a coordinated attack on the immune system, according to a new study from researchers at Penn State. The team found that the thicker the mucus, the better the bacteria are able to swarm. The findings could inform treatments to control the spread of bacteria.

The study, recently published in the journal PNAS Nexus, demonstrates how bacteria use mucus to enhance their ability to self-organise and possibly drive infection.

The experiments, performed using synthetic pig stomach mucus, natural cow cervical mucus and a water-soluble polymer compound called polyvidone, revealed that bacteria coordinate movement better in thick mucus than in watery substances.

According to the researchers, the findings provide insight into how bacteria colonise mucus and mucosal surfaces, and also show how mucus enhances bacterial collective motion, or swarming, which may increase antibiotic resistance of bacterial colonies.

“To the best of our knowledge, our study is the first demonstration of bacteria collectively swimming in mucus,” said Igor Aronson, Huck Chair Professor of Biomedical Engineering, of Chemistry and of Mathematics at Penn State and corresponding author on the paper.

“We have shown that mucus, unlike liquids of similar consistency, enhances the collective behaviour.”

Mucus is essential for many biological functions, explained Aronson. It lines the surfaces of cells and tissues and protects against pathogens such as bacteria, fungi and viruses. But it is also the host material for bacteria-born infections, including sexually transmitted and gastric diseases.

A better understanding of how bacteria swarm in mucus could lead to new strategies to combat infections and the growing problem of antibiotic resistance, according to Aronson.

“Our findings demonstrate how mucus consistency affects random motion of individual bacteria and influences their transition to coordinated, collective motion of large bacterial groups,” Aronson said.

“There are studies demonstrating that collective motion or swarming of bacteria enhances the ability of bacterial colonies to fend off the effect of antibiotics. The onset of collective behaviour studied in our work is directly related to swarming.”

Mucus is a notoriously challenging substance to study because it exhibits both liquid-like and solid-like properties, Aronson explained.

Liquids are typically described by their level of viscosity, how thick or thin the liquid is, and solids are described by their elasticity, how much force it can take before breaking. Mucus, a viscoelastic fluid, behaves as both a liquid and solid.

To better understand how mucus becomes infected, the team used microscopic imaging techniques to observe the collective motion of the concentrated bacteria Bacillus subtilis in synthetic pig stomach mucus and natural cow cervical mucus, which for this purpose are analogous to human mucus.

They compared those results with observations of Bacillus subtilis moving in a water-soluble polymer polyvidone at a wide range of concentrations, from high to low levels of polyvidone.

The researchers also compared their experimental results to a computational model for bacterial collective motion in viscoelastic fluids like mucus.

The team found that mucus consistency profoundly affects the collective behaviour of bacteria: the thicker the mucus, the more likely the bacteria would exhibit collective movement, forming a coordinated swarm.

“We were able to show how the viscoelasticity in mucus enhances bacterial organisation, which in turn leads to coherently moving bacterial groups that cause infection,” Aronson said.

“Our results reveal that the levels of elasticity and viscosity in mucus are a main driver in how bacterial communities organize themselves, which can provide insight into how we can control and prevent bacterial invasion in mucus.”

Aronson explained that the team expects human mucus to exhibit similar physical properties, meaning their findings are also relevant for human health.

“Our results have implications for human and animal health. We’re showing that mucus viscoelasticity can enhance large-scale collective motion of bacteria, which may accelerate how quickly bacteria penetrate mucus protective barrier and infect internal tissues.”

Source: Penn State