Intestinal Microbiota of Childhood: Dysbiosis and Diseases

Abstract

Adult humans harbor 10 bacteria in the gut, comprising >1,000 species, with 160 species per person per fecal sample,1 and this ecosystem plays an important role in human health. While the area of gutmicrobiology in relation to humandiseases is not new and has received medical interest for more than 100 years, technological advancements in the last decade have allowed us to investigate it in a more sophisticated manner. A novel approach is characterized by culture-independent techniques such as amplification of the 16S rRNA gene, which encodes several conserved regions that are exclusive to all bacteria.2 In parallel with the prevailing use of these techniques, the number of articles published in this field is growing rapidly. A search of PubMed for English-language articles using the key words “gut microbiota” found 6,000 articles, among whichmore than 95% were published after 2005. The infant gut undergoes important developmental stages that are entirely dependent on microbial colonization. This development of gut microbiota is considered to begin not at birth but in the fetal period, as meconium is not as sterile as previously assumed.3 The composition of the microbiota in childhood depends on numerous factors including sanitization, mode of delivery (cesarean section or vaginal delivery),maturity at birth (preterm or term birth), infant diet (breastfeeding or formula feeding, and introduction of solid foods), antibiotic usage during infancy, immunization, and geography.1,2 These factors that can alter the microbiota are being studied as potential drivers of the increasing trend in immune-mediated diseases. An ever-expanding number of studies have reported that changes in the composition and activities of gut microbiota can play a significant role in the development of many gastrointestinal as well as nonintestinal diseases.1,2 Dysbiosis is defined as changes in the composition of the gut microbiota andmay be associatedwith several clinical conditions, including obesity and metabolic diseases,4 autoimmune diseases,5 allergy-related diseases,6 acute and chronic intestinal inflammation,7 irritable bowel syndrome,8 necrotizing enterocolitis (NEC),9 and autistic-spectrum disorders.10 Furthermore, a recent review correlates the possible role of dysbiosiswith sudden infant death syndrome.11 Although the precise mechanisms in the relationship between dysbiosis and disease development remain unknown, it has beenhypothesized that there is a “criticalwindow” early in life during which the microbiota can be disrupted in a way thatmay favor the developmentofdisease later in life, based on an early Japanese study.12 The aim of this special issue entitled “Intestinal Microbiota of Childhood: Dysbiosis and Diseases” is to summarize the latest studies of childhood intestinal microbiota. It also discusses the increasing evidence indicating that changes in microbiota during early life affect the development of intestinal and extra-intestinal diseases. This special issue begins with an excellent overview entitled “Early-Life Gut Microbial Composition” by Nagpal and Yamashiro. They summarize the current understanding of acquisition of particular microbial arrays during early life, mainly the first 1,000 days. They also review recent findings about the gut–brain axis, a multicomponent bidirectional signaling system between the gut and the brain. The following review article, entitled “Antibiotics Usage and Intestinal Microbiota” by Tsuji and Kaneko, focuses on antibiotic-associated diarrhea (AAD). Amongmany factors that influence and disrupt the development of the gut microbiota in children, increasing use of broad-spectrum antibiotics in infants in thewesternworld gives rise to disruption of the overall ecology of the gut microbiota and alters the abundance of resident gut bacteria. Both of these factors play an important role in the development of AAD, which is mainly caused by Clostridium difficile. Tsuji and Kaneko summarizes the current understanding of AAD, including preventative treatment using probiotics, which are defined as microorganisms that have a beneficial effect on the body, particularly by maintaining the balance in the composition of the intestinal microbiota. The next five articles discuss increasing evidence indicating that changes in microbiota during early life affect the development of intestinal and extra-intestinal diseases. Despite overall decreases in mortality and morbidity in very low birth weight infants in recent decades, NEC, a devastating condition with high mortality, develops in 5 to 6% of these infants. Lin reviews the critical role of gut microbiota in the pathogenesis of NEC, along with possible therapeutic strategies using probiotics.