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Researchers have developed a diagnostic test to calculate the developmental age of a baby's gut microbiome relative to that baby's health. A similar test could be used by pediatricians to identify and potentially treat infants more than a month behind in normal development. Image Credit: Elsevier Inc.

C-section knocks out infant gut microbiome

A fecal sample analysis of 98 Swedish infants over the first year of life found a connection between the development of a child's gut microbiome and the way baby is delivered.

Babies born via C-section have gut bacteria significantly less like their moms compared to those babies delivered vaginally. The study appears May 11 in Cell Host & Microbe's special issue on "The Host-Microbiota Balance."

The study found nutrition to be a main driver of infant gut microbiome development, specifically the decision to breast-feed or bottle-feed.

"Our findings surprisingly demonstrated that cessation of breastfeeding, rather than introduction of solid foods, is the major driver in the development of an adult-like microbiota," says lead study author Fredrik Bäckhed of The University of Gothenburg, Sweden. "However, the effect of an altered microbiome early in life on health and disease in adolescence and adulthood remains to be demonstrated."

Gut bacteria are suspected to be a source of nutrients and vitamins for the growing infant. For example, our intestinal tenants are able to interact with normal cellular processes in order to produce essential amino acids. Understanding the role individual gut microbes play in metabolism, immunity, and even behavior is a very active area for investigation.

This new study, led by Bäckhed and Jovanna Dahlgren at the University of Gothenburg, Sweden, and Wang Jun at the Beijing Genomics Institute-Shenzhen, China, supports previous observations that most early bacterial colonizers of the gut come from the mother. Investigators noted that while C-section babies receive less of their mother's microbes, mothers still are able to pass some on through their skin and mouth.

Once bacteria take hold in an infant's gut, their populations shift depending on what a child eats.

Researchers believe the cessation of breast-feeding is a significant moment in microbiome development because certain types of bacteria thrive on the nutrients from breast milk. Once these nutrients are not available, other bacteria emerge that are more commonly seen in adults.

"Our results underscore the role of breast-feeding in the shaping and succession of gut microbial communities during the first year of life," say the authors. "The gut microbiota of children no longer breast-fed was enriched with species belonging to Clostridia — that are prevalent in adults — such as Roseburia, Clostrium, and Anaerostipes. In contrast, Bifidobacterium and Lactobacillus still dominate the gut microbiota of breast-fed infants at 12 months."

Cell Host & Microbe, Bäckhed et al.: "Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life" http://dx.doi.org/10.1016/j.chom.2015.04.004

Highlights
•Gut microbiomes of 98 mothers and their infants during the first year of life was assessed

•Cessation of breast-feeding drives the maturation of the infant gut microbiome

•Shifts in signature species demonstrate nonrandom transitions in the infants’ gut

•Changes in nutrient and xenobiotic metabolism mark maturation of the gut microbiome

Summary
The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.

The Infant Gut and Antibiotics: Long-Term Effects

Antibiotics account for one quarter of all medications given to children, with a third of prescriptions considered unnecessary. In addition to concerns about antibiotic resistance, these drugs are known to disrupt a child's gut microbiome in ways that a growing amount of evidence suggests may have long-term consequences, including obesity, allergies, and autoimmune diseases.

Based on a review of the literature, biotechnologist Dan Knights, of the University of Minnesota, and colleagues developed a framework for how antibiotics may be acting in the gut to cause these outcomes.

In the case of allergies, the use of antibiotics may eradicate key gut bacteria that help immune cells mature. These cells would have been essential for keeping the immune system at bay when confronted with allergens. Even if these bacteria return, the immune system remains impaired.

"The framework presented here links together the existing epidemiological and mechanistic studies on antibiotics and various gut-mediated disease outcomes," the authors write. "Large, integrated studies designed to focus on short- and long-term impact of antibiotics, in terms of both microbiome composition and disease risk, with careful consideration of the factors presented here, will be critical as we move toward an increased understanding of related disease etiologies."

The researchers also developed a diagnostic test that calculates the developmental age of a baby's gut microbiome relative to healthy babies. A similar test could be used by pediatricians to identify and potentially treat infants more than a month behind normal development.

Cell Host & Microbe, Vangay et al.: "Antibiotics, Pediatric Dysbiosis, and Disease" http://dx.doi.org/10.1016/j.chom.2015.04.006

Abstract
Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome’s responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.

The Gut Microbiome's Role in Asthma

The recent increase in asthma prevalence, especially in children up to age four, has led researchers to consider changes in the gut and airway microbiome as a contributing environmental factor in the development of this treatable, but uncomfortable, condition.

Susan Lynch and Kei E. Fujimura of the University of California San Francisco present the latest research in mice exploring this relationship, especially how specific types of bacteria alter the presence of different immune cells.

Though still an emerging body of work, Lynch and Fujimura believe there is evidence manipulating the airway/gut microbiome at an early age could lead to new strategies to prevent or manage asthma.

Cell Host & Microbe ,Kei E. Fujimura, Susan V. Lynch: "Microbiota in Allergy and Asthma and the Emerging Relationship with the Gut Microbiome"  http://dx.doi.org/10.1016/j.chom.2015.04.007

Abstract
Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature.

Cell Host & Microbe, published by Cell Press, is a monthly journal that publishes novel findings and translational studies related to microbes (which include bacteria, fungi, parasites, and viruses). The unifying theme is the integrated study of microbes in conjunction and communication with each other, their host, and the cellular environment they inhabit. For more information, please visit http://www.cell.com/cell-host-microbe. To receive media alerts for Cell Host & Microbe or other Cell Press journals, contact press@cell.com.

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