Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability

Abstract

The gut microbiome plays a key role in human health. This community is dynamic during the first three years of life, before stabilizing to an adult-like state. However, relatively little is known about the impact of environmental factors on the developing human gut microbiome. Here we report a longitudinal study of the gut microbiome based on DNA sequence analysis of monthly stool samples and clinical information from 39 children, approximately half of whom received multiple courses of antibiotics during the first three years of life. While the gut microbiome of most vaginally born children was dominated by Bacteroides species, we found that all four children born by Cesarean section and approximately 20% of vaginally born children lacked Bacteroides in the first six to eighteen months. Our longitudinal sampling, coupled with whole-genome shotgun sequencing, allowed us to detect strain-level variation as well as the abundance of antibiotic resistance (AR) genes. The microbiota of antibiotic-treated children was less diverse at the level of both species and strains, with some species often dominated by single strains. In addition, we observed short-term composition changes between consecutive samples from children treated with antibiotics. AR genes carried on microbial chromosomes showed a strong peak in abundance after antibiotic treatment followed by a sharp decline, whereas some genes on mobile elements persisted longer after the end of antibiotic therapy. Our results highlight the value of dense longitudinal studies with high-resolution strain profiles in studying the establishment and response to perturbation of the infant gut microbiome.

Bacterial Fecal Microbiota in Healthy Subjects and Inpatients with <i>Clostridium difficile</i> Infection

“…Advances in next-generation sequencing technologies have emerged in gut microbiota studies, but limitations notwithstanding, DGGE can also provide good qualitative analyses of bacterial compositions and can reveal the major populations of the studied communities. In this work, it was remarkable how bacterial diversity in the intestine from individuals submitted to antimicrobial therapy was dramatically affected, which was previously reported [23] [24] [25]. This dysbiosis allows that the intestinal environment becomes susceptible to opportunistic pathogens like C. difficile, leading to a CDAD.…”

Impact of Early-Life Antibiotic Use on Gut Microbiota of Infants

“…An increased incidence of antibiotic resistance genes observed in antibiotic-exposed children after treatment [29]. The presence of antibiotic resistance genes rose sharply and rapidly during antibiotic treatment and then declined swiftly after antibiotic therapy, whereas the antibiotic resistance genes still presented after antibiotic therapy discontinued for much longer periods of time.…”

“…Meropenem, ticarcillin-clavulanate and cefotaxime treatments were associated with decreased species richness; gentamicin and vancomycin had variable effects on species richness [33]. One of the key motivations of microbiome research is that the microbial population of early childhood is crucial to human health because the decreased diversity of gut microbiota will cause some allergies and autoimmune diseases [29].…”

“…Recent research of Bokulich et al has demonstrated that antibiotic exposures, cesarean section and formula feeding will significantly diminish the diversity and stability of gut microbiota [19]. In collaboration with a team of Finnish researchers they have worked with for several years, the Massachusetts General Hospital team enrolled a group of 39 children in 3 years [29]. During the study period, they collected their fecal samples and found decreased microbial diversity and increased shortterm composition changes in the gut microbiota of antibiotic-treated children [30].…”

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

“…Metagenome wide association studies (MWAS) were also used for checking resilience after dysbiosis induced by drugs, such as antibiotics or anticancer chemotherapies [50][51][52].…”