Probiotic-Induced Modulation of Microbiota Composition and Antibiotic Resistance Genes Load, an In Vitro Assessment.

The imbalance of the gut microbiota (GM) is known as dysbiosis and is associated with disorders such as obesity. The increasing prevalence of microorganisms harboring antibiotic resistance genes (ARG) in the GM has been reported as a potential risk for spreading multi-drug-resistant pathogens. The objective of this work was the evaluation, in a fecal culture model, of different probiotics for their ability to modulate GM composition and ARG levels on two population groups, extremely obese (OB) and normal-weight (NW) subjects. Clear differences in the basal microbiota composition were observed between NW and OB donors. The microbial profile assessed by metataxonomics revealed the broader impact of probiotics on the OB microbiota composition. Also, supplementation with probiotics promoted significant reductions in the absolute levels of tetM and tetO genes. Regarding the blaTEM gene, a minor but significant decrease in both donor groups was detected after probiotic addition. A negative association between the abundance of Bifidobacteriaceae and the tetM gene was observed. Our results show the ability of some of the tested strains to modulate GM. Moreover, the results suggest the potential application of probiotics for reducing the levels of ARG, which constitutes an interesting target for the future development of probiotics.

Old Folks, Bad Boon: Antimicrobial Resistance in the Infant Gut Microbiome.

The development of the intestinal microbiome in the neonate starts, mainly, at birth, when the infant receives its founding microbial inoculum from the mother. This microbiome contains genes conferring resistance to antibiotics since these are found in some of the microorganisms present in the intestine. Similarly to microbiota composition, the possession of antibiotic resistance genes is affected by different perinatal factors. Moreover, antibiotics are the most used drugs in early life, and the use of antibiotics in pediatrics covers a wide variety of possibilities and treatment options. The disruption in the early microbiota caused by antibiotics may be of great relevance, not just because it may limit colonization by beneficial microorganisms and increase that of potential pathogens, but also because it may increase the levels of antibiotic resistance genes. The increase in antibiotic-resistant microorganisms is one of the major public health threats that humanity has to face and, therefore, understanding the factors that determine the development of the resistome in early life is of relevance. Recent advancements in sequencing technologies have enabled the study of the microbiota and the resistome at unprecedent levels. These aspects are discussed in this review as well as some potential interventions aimed at reducing the possession of resistance genes.

Association between diet and fecal microbiota along the first year of life.

Extensive work has established the importance of the gut microbiota during the first years of life. However, there are few longitudinal studies describing the role of infants' diet on the evolution of the fecal microbiota and their metabolic activity during this stage. The aim of this work was to explore the impact of diet on the composition of the major intestinal microorganisms and their main microbial metabolites from birth to 12 months. This is a longitudinal prospective study of diet and fecal microbiota. Bacterial groups levels were determined by qPCR and short-chain fatty acids (SCFAs) concentrations by gas chromatography. Information from self-administered questionnaires about general characteristics and food frequency were obtained from a cohort of 83, Spanish and full-term, infants at 15, 90, 180 and 365 days of age. Results revealed that Enterobacteriaceae decrease in weaning period contrary to Bacteroides group and Clostridium cluster IV. CONCLUSION: our study supports weaning period as a key step for gut microbiota transition and suggests the importance of the consumption of dietary fiber with the increase of certain bacterial groups as Clostridium cluster IV, which could be beneficial for the host. Finally, studies specially designed to analyze the production and the excretion of SCFAs in children are needed to understand how diet could influence in this process.

Impact of intrapartum antibiotics on the developing microbiota: a review.

The perinatal period sets the basis for the later physiological and immune homeostasis of the individual, with the intestinal microbiota being an important contributor to driving this homeostasis development. Therefore, the initial establishment and later development of the microbiota during early life may play a key role in later health. This early establishment of the intestinal microbiota is known to be affected by several factors, with gestational age, delivery mode, and feeding habits being extensively studied ones. Other factors are not so well understood, although knowledge has been accumulating in the last years. Among them, a factor of great relevance is the effect of perinatal exposure to antibiotics. Administration of intrapartum antimicrobial prophylaxis (IAP) to women during the delivery process represents the most common form of exposure to antibiotics during the perinatal period, present in around 30% of deliveries. During the last decade, evidence has accumulated demonstrating that IAP alters intestinal microbiota development in neonates. Moreover, recent evidence indicates that this practice may also be altering the infant intestinal resistome by increasing the levels of some antibiotic resistance genes. This evidence, as reviewed in this manuscript, suggests the interest in promoting the rational use of IAP. This practice has significantly reduced the risk of neonatal infections, but now the accumulating knowledge suggests the need for strategies to minimize its impact on the neonatal microbiota establishment.

Role of Bifidobacteria on Infant Health.

Bifidobacteria are among the predominant microorganisms during infancy, being a dominant microbial group in the healthy breastfed infant and playing a crucial role in newborns and infant development. Not only the levels of the Bifidobacterium genus but also the profile and quantity of the different bifidobacterial species have been demonstrated to be of relevance to infant health. Although no definitive proof is available on the causal association, reduced levels of bifidobacteria are perhaps the most frequently observed alteration of the intestinal microbiota in infant diseases. Moreover, Bifidobacterium strains have been extensively studied by their probiotic attributes. This review compiles the available information about bifidobacterial composition and function since the beginning of life, describing different perinatal factors affecting them, and their implications on different health alterations in infancy. In addition, this review gathers exhaustive information about pre-clinical and clinical studies with Bifidobacterium strains as probiotics in neonates.

Effect of Intrapartum Antibiotics Prophylaxis on the Bifidobacterial Establishment within the Neonatal Gut.

Antibiotics are important disruptors of the intestinal microbiota establishment, linked to immune and metabolic alterations. The intrapartum antibiotics prophylaxis (IAP) is a common clinical practice that is present in more than 30% of labours, and is known to negatively affect the gut microbiota composition. However, little is known about how it affects to Bifidobacterium (sub)species level, which is one of the most important intestinal microbial genera early in life. This study presents qualitative and quantitative analyses of the bifidobacterial (sub)species populations in faecal samples, collected at 2, 10, 30 and 90 days of life, from 43 healthy full-term babies, sixteen of them delivered after IAP use. This study uses both 16S rRNA-23S rRNA internal transcribed spacer (ITS) region sequencing and q-PCR techniques for the analyses of the relative proportions and absolute levels, respectively, of the bifidobacterial populations. Our results show that the bifidobacterial populations establishment is affected by the IAP at both quantitative and qualitative levels. This practice can promote higher bifidobacterial diversity and several changes at a compositional level. This study underlines specific targets for developing gut microbiota-based products for favouring a proper bifidobacterial microbiota development when IAP is required.

Early-Life Development of the Bifidobacterial Community in the Infant Gut.

The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA-23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged.

Donated Human Milk as a Determinant Factor for the Gut Bifidobacterial Ecology in Premature Babies.

Correct establishment of the gut microbiome is compromised in premature babies, with Bifidobacterium being one of the most affected genera. Prematurity often entails the inability to successfully breastfeed, therefore requiring the implementation of other feeding modes; breast milk expression from a donor mother is the recommended option when their own mother's milk is not available. Some studies showed different gut microbial profiles in premature infants fed with breast milk and donor human milk, however, it is not known how this affects the species composition of the genus Bifidobacterium. The objective of this study was to assess the effect of donated human milk on shaping the gut bifidobacterial populations of premature babies during the first three months of life. We analyzed the gut bifidobacterial communities of 42 premature babies fed with human donor milk or own-mother milk by the 16S rRNA-23S rRNA internal transcriber spaces (ITS) region sequencing and q-PCR. Moreover, metabolic activity was assessed by gas chromatography. We observed a specific bifidobacterial profile based on feeding type, with higher bifidobacterial diversity in the human donor milk group. Differences in specific Bifidobacterium species composition may contribute to the development of specific new strategies or treatments aimed at mimicking the impact of own-mother milk feeding in neonatal units.