Treating babies with antibiotics in the first week of life is linked with a decrease in healthy bacteria necessary amongst others to digest milk and an increase in antimicrobial resistance, research suggests.
Experts say that clinicians should consider using antibiotics in a way that causes least harm to the newborns microbiome—the community of microbes that live in our body.
However, experts say that in most cases the antibiotics are prescribed unnecessarily as only a small proportion of those who receive the drugs are eventually diagnosed with an infection.
This overprescription is to ensure early treatment for those who are ultimately found to have an infection as any delay may quickly become life-threatening.
Researchers from the Universities of Edinburgh and Birmingham, and the Spaarne Hospital and University Medical Centre Utrecht, The Netherlands, conducted a clinical trial involving 227 babies to analyse how antibiotics affect a newborn’s microbiome.
Some 147 infants with suspected sepsis received one of three standard antibiotic treatments. Their outcomes were compared with those of 80 babies with no suspected infections and who were not prescribed an antibiotic.
All babies had a rectal or faecal sample taken before and after treatment, and at one, four and 12 months of age. The samples were analysed for the microbes that made up their newly forming microbiome and for bacterial genes related to antimicrobial resistance.
For newborns that had been prescribed antibiotics, there was found to be a significant decrease in the levels of different Bifidobacterium species compared with babies who had no antibiotic treatment.
These microbes aids in the digestion of human breast milk and promotes gut health, while also supporting the immune defence against infection.
The team also found an increase in potentially disease-causing bacteria and in the number and abundance of genes related to antimicrobial resistance in the group that received antibiotics.
Though gradually recovering over time, the changes to the microbiome and to antimicrobial resistance genes persisted for at least 12 months and did not improve with breastfeeding, which is known to help a baby’s immune system.
Professor Debby Bogaert, Chair of Paediatric Medicine at the University of Edinburgh and study lead, said: “We were surprised with the magnitude and duration of the effects of broad spectrum antibiotics on the infants’ microbiome when compared to effects of those same antibiotics on adults’ microbiota. This is likely because the antibiotic treatment is given at a time that infants have just received their first microbes from their mother and have not yet developed a resilient microbiome.”
Of the three antibiotic treatment regimens tested, the combination of penicillin and gentamicin, was found to have the least detrimental effect on a baby’s gut microbiome and the number of antimicrobial resistance genes that emerge.
The researchers conclude this particular combination of antibiotics should be preferably prescribed when treating suspected infections in newborns.
Dr. Marlies van Houten, general paediatrician at the Spaarne Hospital, the Netherlands, and co-Principal Investigator of the study, said “The fact that start of antibiotic treatment rather than duration seems to be responsible for the damage to the microbiome underlines we need better biomarkers or biological predictors to more accurately determine which infant will develop an infection and thus require antibiotics, and which will not.”
Prof Willem van Schaik, Professor of Microbiology and Infection at the University of Birmingham, said: “It is particularly troubling that following antibiotic therapy in newborns we observed a strong increase in Klebsiella and Enterococcus species which are both important multidrug-resistant pathogens.
“This underlines the importance of further studies into balancing the need and effectiveness of these antibiotics and the risk of the emergence of genes linked with resistance. There may also be scope to develop new interventions, like live biotherapeutics—a treatment that is produced by or involving living cells—to effectively restore the composition of the infant gut microbiome after antibiotic therapy.”
The findings are published in Nature Communications.
Antibiotics are lifesaving drugs, due to their powerful ability to battle infections. Since the discovery of penicillin in 1928, numerous antibiotics have been described . Among them, beta-lactams are the most-commonly administered compounds and make up 65% of the antibiotic market . Antibiotics are also extensively used for prophylactic purposes, and they are by far the most common prescription drugs given in the perinatal and neonatal environment, being present in more than 30% of labours [3,4,5]. In this context, the administration of intrapartum antibiotic prophylaxis (IAP) is commonly used for the prevention of early-onset Group-B-streptococci (GBS) infection, in pre-labour rupture of membranes or C-section deliveries to avoid surgical infections [3,6]. However, the use of antibiotics also presents disadvantages, such as promoting antimicrobial resistance, adverse drug events or alterations of the gut microbiota [7,8,9].
The gut microbiota is an ever-changing and complex microbial ecosystem harboured by the gastrointestinal tract (GIT). The microbiota is a key factor in a range of biological processes in the host [10,11,12,13]. After birth, the GIT is rapidly colonised by a wide diversity of microorganisms. Accumulating evidence shows that a correct establishment of this microbiota in the early days of life plays an important role in the reduction of the later development of chronic diseases, such as obesity, allergies, infections, inflammatory or brain disorders, and is an overall determinant for the health of the individual [14,15,16]. Thereby, the period of the gut microbiota colonisation and establishment constitutes a critical window-of-opportunity for its modulation towards a healthy status [17,18,19].
The gut microbiota establishment begins with the settlement of facultative anaerobes and aerotolerant microorganisms, such as enterobacteria or lactobacilli, which pave the way by reducing the oxygen in the gut to the colonisation by other strict anaerobic bacteria, such as bifidobacteria or bacteroides [20,21]. Several factors have an impact in shaping the gut microbiota colonisation process [6,14,19,22,23]. Among them, antibiotics are one of the most pivotal factors promoting alterations on the intestinal microbiota establishment at the beginning of life, linked to immune and metabolic alterations [24,25,26].
Animal studies have shown that when the early-life gut microbiota is altered by antibiotics, enduring physiological effects are observed, even though there is a later microbiota restoration [27,28,29,30,31]. On the other hand, different epidemiological studies have demonstrated the association between early exposure to antibiotics and different diseases, such as allergy [32,33], asthma [31,34], celiac disease [35,36], overweight [37,38,39,40] or inflammatory bowel disease .
In this regard, it is proven that early-life antibiotic treatment disrupts the proper and natural development of gut microbiota with potential negative influence on later health [42,43,44]. During the last years, several studies have seen the advent reporting an impact on the gut microbiota after IAP treatment. Lower relative proportions of Actinobacteria and Bacteroidetes and increased of Proteobacteria and Firmicutes were observed during the first weeks of life, with Bifidobacterium being one of the most affected genera [45,46,47,48].
Nogacka et al., by using 16S rRNA gene profiling of faeces, observed reduced proportions of Bifidobacteriaceae family in full-term babies during the first days of life after IAP treatment , which is in good agreement with the results obtained by Corvaglia et al. by using q-PCR for Bifidobacterium genus . Moreover, Mazzola et al.  also reported lower levels of Bifidobacterium at seven days of life. These differences were also observed at a later age, even at 6 and 12 months , with a higher impact of IAP even than that of later administration of oral antibiotics in infants [50,51].
Bifidobacterium is a genus belonging to the Actinobacteria phylum and is regarded as a keystone taxon in the gut microbiota early in life, with a strong eco-physiological impact on microbiota composition and function [52,53,54]. Some species can dominate the gut of breast-fed infants [55,56,57]. Convincing evidence has accumulated showing that the presence of bifidobacteria in the gut is associated with health improvement [53,58].
This is particularly true in the case of infants. In the early gut microbiota, bifidobacteria drive the intestinal microbiome development and their removal or failure to colonise may lead to the development of chronic diseases . Several studies have shown lower levels or reduced relative abundances of bifidobacteria on infant populations in different scenarios, such as prematurity, obesity, later sepsis, colics [19,59,60,61,62].
This occurs because the levels and diversity of bifidobacteria depend on different perinatal factors, as was reported in a recent publication . Among them, antibiotics deeply affected the Bifidobacterium genus, which could disrupt the crosstalk with the immune system . However, the impact of IAP on gut-specific bifidobacterial populations is still unexplored.
To date, the studies exploring this field have focused their investigations on using the 16S rRNA gene sequencing approach, quantification of the Bifidobacterium genus by q-PCR, or hybridisation-based technique. However, this has provided limited knowledge on the impact of IAP at lower taxonomical levels.
To overcome this limitation, developing next-generation techniques, such as the sequencing of the Internally Transcribed Spacer (ITS) within the rRNA locus , was useful as marker of Bifidobacterium species, as it has been demonstrated in studies focused on the vertical transmission of bifidobacteria , the effect of using donor and own-mother’s milk on the premature bifidobacterial community  or the impact of several perinatal factors on the establishment of Bifidobacterium species in premature and full-term babies .
In this context, by using the ITS sequencing technique as a marker of bifidobacterial (sub)species and q-PCR, we aimed at exploring the effect of the IAP on the establishment and development of the bifidobacterial populations in full-term babies during the first three months of life.
reference link : https://www.mdpi.com/2076-2607/9/9/1867/htm
More information: Marta Reyman et al, Effects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial, Nature Communications (2022). DOI: 10.1038/s41467-022-28525-z