by University of British Columbia

Micronutrient deficiencies reshape gut bacterial community. Weanling C57Bl/6N male mice (n = 10) were given a control or multiple low-micronutrient diet (deficient in vitamin A, B12, B9 (folate), zinc and iron) ad libitum for 28 d. Shotgun metagenomics sequencing was performed on mouse fecal samples collected at Days 0 and 28. Fresh fecal samples were also plated on MacConkey agar and Enterobacteriaceae quantified (c.f.u.). a, Experimental design. b,c, Bar plots at the phylum level by group and by individual mouse. Bars represent mean relative abundance. All taxa with <1% mean abundance were grouped with undefined taxa in ‘Unknown/Other’. d, Shannon alpha diversity of bacteria at Day 0 (P = 0.77) and Day 28 (P = 0.002) (two-sided Wilcoxon test). e, Bray–Curtis beta diversity of bacteria by day and diet treatment. Differences were observed at Day 28 (P = 0.0001), but not at Day 0 (P = 0.28) (two-sided PERMANOVA, all statistics in Source Data). Ellipses represent 95% confidence intervals. f, Enterobacteriaceae c.f.u. counts at Day 0 (n/s, not significant) and Day 28 (P < 0.0001) (two-sided Wilcoxon tests). For all boxplots: center lines, upper and lower bounds, and upper and lower whiskers show median values, 25th and 75th quantiles, and the largest and smallest non-outlier values, respectively. Outliers are defined as having a value >1.5 × interquartile range (IQR) away from the upper or lower bounds. All statistical tests are two-sided. No P values were corrected. Data shown are from 10 individual mice per group. Credit: Nature Microbiology (2023). DOI: 10.1038/s41564-023-01519-3

University of B.C. researchers have uncovered startling connections between micronutrient deficiencies and the composition of gut microbiomes in early life that could help explain why resistance to antibiotics has been rising across the globe.

The team investigated how deficiencies in crucial micronutrients such as vitamin A, B12, folate, iron, and zinc affected the community of bacteria, viruses, fungi and other microbes that live in the digestive system.

They discovered that these deficiencies led to significant shifts in the gut microbiome of mice—most notably an alarming expansion of bacteria and fungi known to be opportunistic pathogens.

Importantly, mice with micronutrient deficiencies also exhibited a higher enrichment of genes that have been linked to antibiotic resistance.

"Micronutrient deficiency has been an overlooked factor in the conversation about global antibiotic resistance," said Dr. Paula Littlejohn, a postdoctoral research fellow with UBC's department of medical genetics and department of pediatrics, and the BC Children's Hospital Research Institute. "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."

Bacteria naturally possess these genes as a defense mechanism. Certain circumstances, such as antibiotic pressure or nutrient stress, cause an increase in these mechanisms. This poses a threat that could render many potent antibiotics ineffective and lead to a future where common infections could become deadly.

Antibiotic resistance is often attributed to overuse and misuse of antibiotics, but the work of Dr. Littlejohn and her UBC colleagues suggests that the 'hidden hunger' of micronutrient deficiencies is another important factor.

"Globally, around 340 million children under five suffer from multiple micronutrient deficiencies, which not only affect their growth but also significantly alter their gut microbiomes," said Dr. Littlejohn.

"Our findings are particularly concerning as these children are often prescribed antibiotics for malnutrition-related illnesses. Ironically, their gut microbiome may be primed for antibiotic resistance due to the underlying micronutrient deficiencies."

The study, published this week in Nature Microbiology, offers critical insights into the far-reaching consequences of micronutrient deficiencies in early life.

It underscores the need for comprehensive strategies to address undernutrition and its ripple effects on health. Addressing micronutrient deficiencies is about more than overcoming malnutrition, it may also be a critical step in fighting the global scourge of antibiotic resistance.

More information: Paula T. Littlejohn et al, Multiple micronutrient deficiencies in early life cause multi-kingdom alterations in the gut microbiome and intrinsic antibiotic resistance genes in mice, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01519-3

Journal information: Nature Microbiology 

Provided by University of British Columbia