Malnutrition Another Cause of Antibiotic Resistance: Study

Unique link found in mice offers another possible explanation to the rising global threat that kills 35,000 Americans annually. 

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A new gut microbiome study has offered important insights into why antibiotic resistance is on the rise among populations with nutrient deficiencies.

The gut microbiome is made up of trillions of bacteria, viruses, and fungi that live within the gastrointestinal tract and assist with digestion, metabolism, immunity, and other functions. Antibiotic resistance happens when pathogenic bacteria outsmart the drugs that are meant to kill them and create infections that are difficult or impossible to treat.

Researchers at the University of British Columbia (UBC) found that deficiencies in the micronutrients folate, iron, and zinc, as well as vitamins A and B12, led to significant changes in the gut microbiomes of mice, “most notably an alarming expansion of bacteria and fungi known to be opportunistic pathogens,” reported UBC.

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The study results, published on Nov. 16 in Nature Microbiology, also found that these deficiencies led to more bacteria with genes that have been linked to antibiotic resistance.

The researchers say these genes are a defense mechanism that bacteria use when pressure from antibiotics or nutrient deficiency threatens them. In other words, malnutrition can trigger the same changes in bacteria that antibiotics do.

The Threat of Antibiotic Resistance

Most research on the threat of antibiotic resistance has focused on the role of antibiotics themselves.

Pathogenic bacteria resistant to antibiotics are considered a growing threat to global health, creating superbugs that could have a devastating effect on global populations. When used appropriately, antibiotics kill infection-causing bacteria and save lives. But most antibiotics are broad spectrum, meaning even when their use is warranted, they still kill more than just the problematic microbes. They also kill off the beneficial bacteria, many of which are crucial to keeping pathogenic microbes from establishing themselves. For this reason, antibiotics can leave people vulnerable to infectious microorganisms.

Overuse of antibiotics also overexposes bacteria to the antibiotic, giving these microbes more pressure to develop resistance. Efforts to curtail the overprescription of antibiotics in people and animals have had limited success and antibiotic resistance has only accelerated.

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Figuring out how to resolve this issue has become an urgent area of investigation for researchers and health organizations. Antibiotic resistance can affect people in any country and at any age.

Each year in the United States, 2.8 million people experience an antibiotic-resistant infection, and more than 35,000 people die as a result, according to the U.S. Centers for Disease Control and Prevention.

The problem is leading to longer hospital stays, increased medical costs, and higher mortality. Each hospitalization or surgery increases the risk of someone acquiring an antibiotic-resistant infection because antibiotic-resistant bacteria are often found in hospitals. The new research may explain why a poor diet—and in particular, a lack of access to quality food—may also be a risk factor.

‘Opportunistic Pathogens’

The new research opens up another avenue to study antibiotic resistance and hopefully slow its progression.

The findings also point to a potentially vicious cycle created because children with malnutrition-related illnesses are often prescribed antibiotics, which may then make them vulnerable to infection with antibiotic-resistant bacteria.

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“Ironically, their gut microbiome may be primed for antibiotic resistance due to the underlying micronutrient deficiencies,” said Paula Littlejohn, a postdoctoral research fellow with UBC’s medical genetics and pediatrics departments and the BC Children’s Hospital Research Institute.

“Micronutrient deficiency has been an overlooked factor in the conversation about global antibiotic resistance,” she said. “This is a significant discovery, as it suggests that nutrient deficiencies can make the gut environment more conducive to the development of antibiotic resistance, which is a major global health concern.”

Growing research indicates that Americans aren’t getting enough micronutrients to support proper immune function. While Americans eat enough calories, much of their food is nutrient deficient, including processed foods and diets heavy in refined grains. 

A 2020 review in Nutrients described this nutrient deficit as a public health concern and cited deficiencies in vitamins A, C, D, and E as the largest among all population groups. Zinc deficiencies are mostly prominent in older adults. 

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The body can store large amounts of vitamin B12—up to 2,000 times the amount typically consumed in a day, according to the National Institutes of Health. Because of these stores, it can take time for deficiencies to develop, and they tend to be in older adults, those with gastrointestinal problems or past surgeries, vegetarians, and infants of mothers who eat a vegan diet. 

Inadequate iron intake is a concern for young children, and many foods are fortified to compensate for the low levels of iron in breast milk. Most micronutrients fall below recommended levels but don’t dip into deficiencies for the vast majority of Americans, according to Oregon State University. However, most of the data collected is based on eating recollection rather than actual nutrient blood testing.

As noted, the mice with micronutrient deficiencies in the study also had a higher number of genes that have been linked to antibiotic resistance.

Genes play a role in antibiotic resistance because bacteria are able to share DNA, meaning that newer gut bugs never exposed to antibiotics can receive antibiotic-resistant genes from the older bacteria in the community that mounted a survival response to the antibiotic. This creates a microbial community that can resist antibiotics and puts the host at risk for deadly infections.

Supporting a Healthy Microbiome

Microbiome research is a relatively new and rapidly growing field of research. Evidence that shows a well-formed microbiome early in life is associated with wellness and a more robust immune response.

Some of the factors associated with a healthy microbiome are vaginal births, breastfeeding, and limited or no exposure to antibiotics. Recent studies have also connected nutrition to a healthy microbiome, including a Nature Communications review article in June that looked at how undernutrition, the microbiome, and child development influence one another in the early years of life.

“Lack of food or inappropriate feeding practices, in addition to higher exposure to pathogens, affect the microbiome with potential impacts on child development. Changes in the composition and maturity of the gut microbiome could correlate with or even contribute to undernutrition,” the study notes. In other words, eating poorly can result in a less healthy microbiome, which in turn can make it more difficult to properly digest food and obtain full nutrition from food eaten.