Years of antibiotic use have fuelled a rise in bacteria that can survive antibiotics. These antibiotic resistant bacteria are competing with and displacing other bacteria that are naturally present in the human gut, where they play a critical role in maintaining good health. Resistant bacteria have led to increased illness and death from diseases that were once easily treatable with antibiotics. Disease ecologist Eric Ng’eno shares findings from his research on how some resistant strains of Escherichia coli bacteria are taking over the guts of people who are otherwise healthy. He suggests how this displacement can be slowed down.
What did you do that’s new?
In every person’s gut there are millions of friendly microbes that help digest food, produce energy, and shield the person from harmful, disease-causing bacteria and other invaders. The microbes that live in the body include bacteria, fungi and viruses. They form a community of microorganisms.
Where people live and work together, healthy microbes spread easily through everyday interactions like handshakes, kissing, and sharing food or water. In this way, people who interact often tend to develop similar gut microbes. We call these the background microbial community.
Disease-causing agents spread in a similar way.
Microorganisms affect the environment around them so as to encourage or prevent the growth of other microorganisms in their community. We wanted to assess whether these microbial interactions play a role in the presence of resistant E. coli in the gut of individuals living in a densely populated urban informal settlement in Nairobi, Kenya.
To do this, we mapped out background microbial communities in people living in different areas across the study region.
We then tested how different background microbial composition identified at the beginning of the study were associated with resistance patterns observed thereafter.
How did you go about it?
To determine the role of the gut microbes, we first built a statistical model that used all three factors that contribute to the spread of antibiotic-resistant bacteria together. These factors are:
- antibiotic use
- spread of bacteria
- background microbial communities in people’s guts.
We measured how well this combined model predicted where resistant E. coli appeared.
Next, we ran a similar model, but this time using background microbial communities as the only predictor. These are the microbes people naturally had in their gut at the beginning of the study.
By comparing the two results, we were able to pinpoint how much the background microbial communities alone drove resistance in this setting. We used E. coli strains identified from faecal samples collected from people living in different locations across the whole study area.
The idea of considering microbial interactions in the analysis of drivers of resistant bacteria carriage isn’t new. But this is the first time where such interactions were considered in an analysis of real-world data.
What did you find?
We showed that the background microbial community largely determined which E.coli strains people in this area ended up carrying.
People who lived in areas where invading resistant bacteria made up a larger share of the local microbial community were more likely to carry resistant E. coli strains. Those in areas where the local microbial communities mostly included the native non-resistant bacteria were less likely to carry resistant E.coli strains. This was the case despite how antibiotics were used and how easily bacteria could spread in these areas.
Antibiotic use and background microbial communities work together. When antibiotics disrupted the gut microbiota of individuals, the native microbes that people had in their guts were quickly displaced by microbial communities present in the surrounding environment. If these replacement microbial communities include invading resistant bacteria, they may create an environment that supports growth of even more resistant bacteria in the invaded guts.
How this process worked varied with the type of antibiotics involved.
Antibiotics that severely disrupted the gut microbiota facilitated direct takeover by microbes present in the surrounding environment.
On the other hand, milder, less universally lethal antibiotics tended to result in varied outcomes. The resistant E. coli has fewer opportunities to take over since these antibiotics preserve the original gut microbiota that compete with incoming microbes.
Why are your findings useful?
These findings highlight that carriage of antibiotic resistant E. coli in community settings is context dependent. Native microbes present in the broader environment shape whether an invading resistant strain established itself or not.
Strategies to minimise antibiotic resistance need, therefore, to be tailored to the local microbial community context. In areas where the background microbial community includes resistant types, measures which minimise disruption or facilitate the spread of harmless microbes should be encouraged.
Broadly speaking, current preventive efforts should always aim at helping natural, diverse, non-resistant microbial communities to reclaim their ground in human populations.
These communities carry the potential for holding back resistant bacteria. The goal is to preserve them.
Minimising the use of antibiotics is key to this effort. Vaccines and hygiene practices which minimise the risk for diseases can help reduce the need for antibiotics.
Where unavoidable, antibiotics need to be used carefully. In addition, there need to be efforts to restore microbes lost with antibiotic use.
In the short term, using probiotics after using antibiotics may be a good strategy. For the long term, people could be encouraged to embrace “farming of the microbiome”. This describes the continuous efforts of creating a culture of good bacteria in the body. People around the world have been doing this for centuries through eating fermented foods, for example, which are naturally packed with the good microbes.
Eric Ng’eno receives funding from the Gates Foundation.
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