First 1000 Days of Life: Consequences of Antibiotics on Gut Microbiota

Abstract

The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. In particular, the process of gut microbiota establishment occurs within this time window. Therefore, determinants interfering with neonatal gut establishment may disrupt its physiological functions and potentially lead to negative health outcomes. Antibiotics are among perinatal determinants that can directly or indirectly affect the pattern of gut bacterial colonization, with a long-lasting impact on intestinal ecosystem functions. In this review, we will examine the impact of antibiotics on the intestinal microbiota during the perinatal period and first years of life, a key interval for development of an individual’s health capital. Further, we will discuss the role of antibiotics during short- and long-term dysbiosis and their associated health consequences.

Neonatal Programming of Microbiota Composition: A Plausible Idea That Is Not Supported by the Evidence

“…In this regard, various epidemiological studies have established statistical associations between early alteration of the intestinal microbiota and the subsequent occurrence of particular pathophysiologies (reviewed by Blottière et al, 2013;Tamburini et al, 2016;Milani et al, 2017;Stinson, 2020). It has been documented in particular in the case of birth by CS (Korpela, 2021;Ríos-Covian et al, 2021) and perinatal antibiotic therapies (Azad et al, 2017;Aires, 2021), but these associations should be viewed with caution due to the possibility of biases relating to reverse causalities and the fact that the repercussions of CS are not limited to modulation of the microbiota (King, 2021). Interventional studies on animal models are more convincing in this respect; to date, several studies have demonstrated associations between early microbiotal perturbations and subsequent physiological consequences (e.g., Cox et al, 2014or Pocheron et al, 2021, demonstrating the need to consider early microbiota alterations in the DOHAD process.…”

“…It is difficult to draw any clear-cut conclusion on the long-lasting impact of early antibiotic treatment in humans, considering the enormous variations in prescriptions [type, dosage and possible combination of antibiotic(s), route and length of administration, indication for the prescription, culture/habit of the clinician] (Stewart and Cummings, 2017;Aires, 2021) and the specificities of the target population (intrapartum or neonatal administration, term or preterm neonates, vaginal or CS delivery) (Dierikx et al, 2020). The picture is further complicated by the possible cumulative nature of antibiotic treatments during neonatal development (Blaser, 2016).…”

“…The picture is further complicated by the possible cumulative nature of antibiotic treatments during neonatal development (Blaser, 2016). However, according to recent reviews (Azad et al, 2017;Edwards, 2017;Dierikx et al, 2020;Aires, 2021), the lasting impacts of perinatal antibiotherapies may be noticeable for a few months but not beyond, depending on the nature of the antibiotics (ATB) and possibly the age at which it was administered. Studies on durations longer than a few months are nevertheless rare.…”

Modeling approaches for probing cross-feeding interactions in the human gut microbiome

“…16S rRNA and metagenomic studies have allowed scientists to evaluate the structure of this community in terms of relative abundance of species (richness), intra and inter-diversity, and metabolic functions [4] . Advances have been made to understand the assembly process in the infant gut microbiota [5] , characterized by a succession of microorganisms, the wide diversity in microbiome compositions in the adult and elderly, the impact of antibiotics on this community, and its resilience [6] , [7] . These advances have contributed to new hypotheses or validations of the role of the gut microbiota in disease.…”

Metabolic Modeling and Bidirectional Culturing of Two Gut Microbes Reveal Cross-Feeding Interactions and Protective Effects on Intestinal Cells

“…The gut microbiota is represented by a complex network of microorganisms occupying different niches in the human gut ( 1 , 2 ). Their abundances change dynamically according to age and perturbations such as antibiotic administration ( 3 – 5 ). The composition and activity of the gut microbiota are influenced by the diet, especially by molecules that escape digestion in the small intestine, rendering them available for fermentation in the large intestine ( 6 ).…”