27 May 2024

Cease & resist

Overuse of antibiotics is known to have detrimental effects; new Teagasc research is examining how antibiotic use in early life affects human and animal microbiota.

Limiting antibiotic use in early life can bolster antimicrobial resistance genes later on in life (Photo: blackCAT/iStockphoto.com)

Antimicrobial resistance (AMR) represents a burgeoning global threat that renders previously effective antimicrobial treatments ineffective against infections. The overuse and misuse of antibiotic and antifungal treatments give rise to multidrug-resistant microorganisms that exhibit resistance to a wide array of antibiotics. AMR not only poses grave challenges in healthcare settings, where infections become increasingly difficult to treat; its ramifications also extend to agricultural and environmental domains where it can jeopardise food security and contaminate natural environments. 

Furthermore, in an era when we understand the importance of the microbiota (the collection of microorganisms in a given habitat or niche) to host health, it is essential to unravel the impact of antibiotics and AMR on this community of microorganisms.

Researchers based at Teagasc Moorepark, in conjunction with APC Microbiome Ireland, recently published a series of five research publications on AMR, highlighting the implications of antibiotic use in early life and the effects of antibiotic use in standard dry cow therapy. A paper published in the journal Microbiome suggests that early life exposure of infants to specific antibiotics could lead to multi-drug resistance; a paper published in Antibiotics suggests that antibiotic use does not benefit standard dry cow therapy.

Additionally, the researchers published two reviews in highly cited publications; one in Trends in Microbiology, ‘Vertical transfer of antibiotics and antibiotic resistant strains across the mother/baby axis’, which reviews the mechanisms of mother-to-infant transmission of antibiotics and antibiotic-resistant strains. Another review, ‘Impact of antibiotics on the human microbiome and consequences for host health’, published in Microbiology Open, discusses the adverse effects of antibiotics on the gut microbiota and thus host health and suggests alternative approaches to antibiotic use.

Lasting effects

Dhrati Patangia, a Post-Doctoral Researcher at Teagasc Moorepark’s Food Research Centre and lead author of the studies, explains some of the findings: “The research highlighted that antibiotic use can have lasting effects that can be observed even months after administration of a single dose. Antibiotic‐induced changes in microbial composition can have a negative impact on host health including reduced microbial diversity, changes in functional attributes of the microbiota and the formation and selection of antibiotic‐resistant strains making hosts more susceptible to infection with pathogens.”

Antibiotic-resistant strains formed can cross the mother-baby axis resulting in vertical transmission, while at the same time transfer of antibiotic resistance genes can occur through the food chain – for instance by consumption of raw milk consisting of antibiotic-resistant bacteria.

Dhrati explains: “Thus, it is pivotal to address the critical balance between the life-saving benefits of antibiotics and the alarming rise of antimicrobial resistance, emphasising the importance of prudent antibiotic usage and the development of innovative antimicrobial agents to safeguard public health and mitigate the far-reaching consequences of antimicrobial resistance.”

As part of this initiative, Dhrati and her co-authors studied the development and transmission of antibiotic-resistance genes in lactating cows and infants in early life.

Dry cow therapy represents one of the few instances where healthy cows get treated with antibiotics, a practice that has been recently regulated against across the EU. This treatment was deemed necessary since animals can become particularly susceptible to infection at drying off.

“We examined colostrum and milk samples from cows across five different farms that were treated with or without antibiotics during the drying-off period,” Dhrati continues.

“The main surprising outcome of this study was that the milk from cows treated with either of two different antibiotic dry cow treatments had different bacteria in their milk, even six months after the treatment, and that these bacteria harboured multiple resistance to antibiotics. It indicates that such treatments contribute to the spread of antibiotic resistance.” The study also highlights the urgent need for alternative treatments to combat infection in production animals.

Early life is a crucial stage for the foundation of microbiota development, which affects the infant’s health and immunity in later life. However, the infant gut microbiota is highly unstable, and several factors affect it – including early-life antibiotic exposure, which can have potentially long-lasting effects. Nevertheless, the long-term longitudinal impact of antibiotic exposure in early life has not been extensively studied; this includes mode of delivery, and how antibiotics affect gut microbiota and the resistome (all the antimicrobial resistance genes within the microbiota).

Early warning

The researchers studied the longitudinal impact of early-life antibiotic use on the microbiota and antibiotic resistance profile in 45 infants from week one to year two of life, Dhrati explains. “We observed that limited treatment in very early life of two antibiotics can lead to an amplification of the resistome later, as it selects for bacteria that presumably carry multidrug resistance from their history, which can complicate treatments in later life.”

With increasing reports of antibiotic resistance genes in infants from their study and other published studies, the researchers investigated the gut resistome profile during early life at a wider geographic level. Many of the species with antibiotic-resistance genes that were highly abundant in the infant gut in early life are well-known pathobionts (capable of causing harm) including Escherichia, Klebsiella, and Citrobacter.

Dhrati concludes: “The abundance of these species, and a diverse range of antibiotic-resistance genes in their genomes, point towards the infant gut acting as a reservoir for antibiotic-resistance genes. This study highlights that the development of antibiotic alternatives is essential along with strategies to maintain a healthy gut microenvironment at this crucial stage of infancy.”

Funding 

Dhrati Patangia received a full Science Foundation Ireland Scholarship to conduct the research as part of the inaugural APC Antimicrobial Resistance Postgraduate Fellowship programme.

Contributors

Dhrati Patangia
Post-Doctoral Researcher,
Teagasc Food Research Centre, Moorepark.

Ghjuvan Grimaud
Post-Doctoral Researcher,
Teagasc Food Research Centre, Moorepark.

Paul Ross
Director of APC Microbiome Ireland, UCC, Cork.

Catherine Stanton
Senior Principal Research Officer,
Food Biosciences Department, Teagasc Food Research Centre, Moorepark.
catherine.stanton@teagasc.ie