Scientists Demonstrate How Antibiotics Can Alter Gut Flora Allowing Infection

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Chemist Direct reviews new research on the changes that occur in the intestinal ecosystem that can lead to infection after antibiotic treatments are given.

Healthy Gut

Probiotic daily supplements help keep gut healthy

Anyone taking antibiotics should be warned about potential side effects...and should consider taking a probiotic supplement if these symptoms linger for more than a few days after antibiotic treatment has finished.

Over one trillion varieties of bacteria live in the gut in thousands of distinct bacterial strains known as microbiota or gut flora. In the past decade much has been learned about this complex microbial ecosystem that resides in every healthy mammal's large intestine, including ours. In this nutrient-rich environment these bacteria work in symbiosis with humans to manufacture vitamins, provide critical training to our immune systems and even guide the development of our own tissues.

In a collaboration of the CSIC, CSISP, University CEU San Pablo and led by Andrés Moya who works at Universitat de València, the first studies of the effect of antibiotics on this gut-microbe ecosystem reveal antibiotics decimate the gut flora in the first few days of treatment. The ecosystem bounces back within a few days, but may take a month or more to regain its former numbers, and some constituent bacterial strains may suffer permanent loss. “Although the research shows for the first time deficiencies in key activities such as a lower capacity to produce proteins,” explains Moya, the study suggests that the gut microbiota “shows less capacity to absorb iron, digest certain foods and produce essential molecules for the organism as well, both during and after the treatment.” 1

A number of intestinal pathogens can cause problems after antibiotic administration and according to this latest study, treatment with antibiotics can alter this symbiosis from early stages of the treatment, said Justin Sonnenburg, PhD, assistant professor of microbiology and immunology and the senior author of the study, to be published online Sept. 1 in Nature. Graduate students Katharine Ng and Jessica Ferreyra shared lead authorship."Antibiotics open the door for these pathogens to take hold. But how, exactly, that occurs hasn't been well understood," Sonnenburg said. In the first 24 hours after administration of oral antibiotics, a spike in carbohydrate availability takes place in the gut, the study says.

This transient nutrient surplus, combined with the reduction of friendly gut-dwelling bacteria due to antibiotics, permits at least two potentially deadly pathogens to get a toehold in that otherwise more forbidding environment. The particular nutrients Sonnenburg's team looked at were sialic acid and fucose, a couple of members of the sugar family. While not household words like glucose, fructose or lactose, these two sugar varieties are produced in every cell in our bodies and are absolutely necessary for our healthy survival.

They are also found in meat, eggs and dairy products. Our resident microbes hold pathogens at bay by competing for nutrients, when that defence falters, as it does shortly after a course of antibiotics begins, marauding micro-organisms such as salmonella or Clostridium difficile can establish beachheads. Once they reach sufficient numbers, these two parasitic invaders can mount intentional campaigns to induce inflammation, a condition that impairs the restoration of our normal gut ecosystem but in which salmonella and C. difficile have learned to prosper.

For the Nature study, the team experimented on mice that had been born and bred in a germ-free environment, and were devoid of bacteria, unlike normal mice, which harbour hundreds of bacterial species in their bowels just as humans do. Into these germ-free mice the Stanford investigators introduced a single bacterial strain, B. theta. In a series of separate experiments, the investigators introduced either S. typhimurium (a salmonella strain) or C. difficile in the B. theta-loaded experimental mice.

Both types of bacteria can cause severe and potentially life-threatening disease associated with antibiotic use. Introducing one friendly and one pathogenic bacteria strain into the guts of the formerly germ-free mice, the scientists were able to show that levels of sialic acid soared to high levels, allowing both pathogens to replicate more rapidly. "The bad guys in the gut are scavenging nutrients that were liberated by the good guys, who are casualties of the collateral damage incurred by antibiotics," said Sonnenburg. "Antibiotics cause our friendly gut bacteria to unwittingly help these pathogens.” 2

When the researchers investigated the effects of antibiotics on mice with normal intestinal ecosystems, they saw the same sialic-acid spike -- and pathogen population explosion -- in the wake of the carnage. If the mice were not exposed to the pathogens, but only treated with antibiotics, the sialic acid concentrations returned to their original levels after about three days post-antibiotic treatment as gut flora began to recover.

"We believe that bacterial pathogens in the gut cause disease in two steps," he continued. "Others have shown that once these pathogens attain sufficient numbers, they use inflammation-triggering tricks to wipe out our resident friendly microbes -- at no cost to the pathogens themselves, because they've evolved ways to deal with it.

"But first, they have to surmount a critical hurdle: In the absence of the inflammation they're trying to induce, they have to somehow reach that critical mass. Our work shows how they go about it after a dose of antibiotics. They take advantage of a temporary spike in available sugars liberated from intestinal mucus left behind by slain commensal microbes."

Sonnenburg said he thinks researchers may someday be able to find drugs that, co-administered with antibiotics, could inhibit the enzymes our friendly gut-bugs use to liberate sialic acid from intestinal mucus, so that a pathogen-nourishing spike doesn't occur. Alternatively, probiotics in the form of bacterial strains that are especially talented at digesting sialic acid could achieve a similar effect. 3

ChemistDirect Superintendant Pharmacist Omar El-Gohary states: “This research demonstrates the complex relationship different types of bacteria living inside our gut that can both help and hinder us. Anyone taking antibiotics should be warned about potential side effects such as diarrhoea and abdominal cramps, and should consider taking a probiotic supplement if these symptoms linger for more than a few days after antibiotic treatment has finished.”


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