B. infantis EVC001 Reduces The Genes In Bacteria That Cause Antibiotic Resistance By 90 Percent

The World Health Organization (WHO) calls antibiotic resistance “one of the biggest threats to global health, food security, and development today,” and the Centers for Disease Control and Prevention (CDC) calls it “one of the biggest public health challenges of our time.” It’s estimated that it costs the US healthcare system alone an estimated $5 billion. More importantly, more than two million people in the U.S. develop antibiotic-resistant infections annually. The worldwide figures are much worse — 200,000 infants die each year globally as a result of such infections.

Despite stark warnings, there does not appear to be any evidence that overuse of antibiotics — whether through prescriptions, non-approved use, or use on livestock — is decreasing, so we may expect the problem to get worse unless we find effective new approaches, and some are predicting that the death toll could rise to 10 million a year.

Limiting the spread of antibiotic resistance genes (ARGs) — the genes that essentially turn normal pathogens into what are commonly referred to as “superbugs” — is tricky. Aside from being difficult to kill, simply following the conventional approach of looking for more powerful drugs presents the possibility that harmful bacteria will eventually adapt to those treatments as well, ultimately creating even more deadly strains. This leaves the global healthcare community with few options for dealing with this issue. On the other hand, discovering a way to reduce antibiotic resistance without triggering additional resistance could save millions of lives worldwide.

Healthy babies can be vectors for spreading antibiotic resistance-carrying genes

We know that antibiotic resistance genes are acquired in early life and can have long-term sequelae, but what’s alarming is that in larger hospitals – where microbes are likely to develop antibiotic resistance – 40% of infections in newborns currently resist standard treatments. The situation may in fact be even more alarming than that. Our study, published in Antimicrobial Resistance and Infection Control, found higher than expected levels of antibiotic-resistant genes (ARGs) in healthy, breastfed infants. Many of the organisms identified as carriers of ARGs are causative agents of very serious conditions such as EOS, LOS, and NEC.

This means that otherwise healthy infants not only have a higher risk of developing untreatable infections later on, but also that they may be vectors in the spread of antibiotic resistance gene-carrying bacteria to their caregivers and family-members.

B. infantis starves out ARG-carrying bacteria

However, our study also found that infants fed Bifidobacterium longum subsp. infantis EVC001 (aka B. infantis EVC001) showed a 90 percent lower level of ARGs compared to those in the control group, driven largely by a reduction in Escherichia, Clostridium, and Staphylococcus (these were reduced by 99 percent). Notably, E. coli isolated from the stool of control infants in this study were shown to be resistant to a broad range of antibiotics, such as ampicillin, which is commonly used to treat a number of infections, including pneumonia.

In short, B. infantis may be a very compelling option for curbing the further spread of antibiotic resistant bacteria. B. infantis achieves this reduction in ARGs by outcompeting ARG-carrying gut microbes for HMOs and producing lactate and acetate resulting in lower colonic pH levels, which create an inhospitable environment for ARG-carrying bacteria.

Figure courtesy Michael Burke, MSR Communications, LLC

The study was conducted using shotgun metagenomics in fecal samples from 60 healthy term exclusively breastfed infants, half of whom were fed B. infantis EVC001. Among the 29 treatment group infants, it was observed that B. infantis EVC001 quickly dominated the gut microbiome, representing 88% of the total relative abundance in the microbial community. By comparison, in the control group, total Bifidobacterium composed only 38% of the microbiome on average. After cross-sample normalization, 38 ARGs identified in the study were significantly lower in the B. infantis-fed group than in the control group. These findings support a recent study published in mSphere by UC Davis and icddr,b which found that children with higher levels of Bifidobacterium had reduced levels of antimicrobial resistance (AMR) genes.

Figure courtesy Michael Burke, MSR Communications, LLC

A safer approach to curbing antibiotic resistance

In contrast to the conventional approach of searching for stronger medications, B. infantis is not a new treatment, but rather a reintroduction of something that naturally belongs in the baby’s gut. It is a highly-studied organism with a long history of evolutionary adaptation to the breastfed infant.

Essentially nature has given us a way to protect against superbugs, but we’ve unintentionally all but eliminated it from our own microbiomes. B. infantis is a beneficial bacterial subspecies historically found in a healthy baby’s gut microbiome. However, as an unintended consequence of modern medical practices like C-sections and antibiotic usage, B. infantis has become scarce. We know this because it’s disappearance in our population has led to a significant elevation in fecal pH over the past 100 years.

Consequently, B. infantis supplementation is an easy and safe option for reducing antibiotic resistance genes (ARGs), with no side effects, propensity to trigger additional resistance mechanisms, or other potential downsides. It isn’t a new treatment, per se, but rather a reintroduction of something that naturally belongs in the baby’s gut.

About The Author

Giorgio Casaburi

Giorgio Casaburi, Ph.D., is a Senior Bioinformatics Scientist at Evolve BioSystems, Inc. Giorgio studies the infant gut microbiome and his primary research interest is in the development and application of novel bioinformatics techniques to high-throughput DNA sequencing data analysis for the advancement of life sciences. His research focuses on host-microbiome interactions including both human and environmental fields. Prior to Evolve BioSystems, Giorgio worked at NASA, where he launched squids into space to discover how beneficial commensal bacteria protect the host against the stress of zero gravity. His unique combination of training experiences in the hospital, laboratory and the supercomputer has given him a broad understanding of biomedical research in the era of “Big Data” biology.

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