Factors host genetics, method of childbirth, maternal diabetes status,

Factors affecting the composition of human microbiome and its importance to human healthy



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Human microbiota plays a role on part of the human body metabolism and regulation. Quickly developing sequencing and analytical techniques have allowed us to have a better understanding of the human microbiome. Factors such as host genetics, method of childbirth, maternal diabetes status, mucin glycosylation and administration of Antibiotic could have an impact on the microbial colonization. This article discusses recent studies on investigating the effect of different factors on the composition of the microbiome and its consequences. A few application on how altering the intestinal microbiota could ameliorate or prevent disease states.



The human microbiota is a community of microorganisms include viruses, bacteria and archaea. In each person, microbiota contains about 10-100 trillion symbiotic microbial cells, where most of them would be bacteria in the gut. 1 In the human intestinal tract, 1014 microbes can be found, with a density of 101—1012cells/ml, the highest number has ever recorded in any microbial habitats. 2 Where the Human microbiome is all the genes these cells contain. In the mid-1880s, it was first proven that microorganism is part of the human system by Theodor Escherich, who observed E.Coli in the intestinal flora of both healthy and children with diarrhoea. In the 20th century, more microorganisms were identified from samples isolated from oral cavities, gastrointestinal tract, skin and nasal cavity, and were considered as the human microbiota. The concept and of human microbiome are primarily studied in the 21st century, where rapidly developing analytical technique and sequencing method are improving our understanding of the human microbiome. DNA-based analyses generate enormous data set which gave us more information on the composition and functions of the microbial communities. E.g. the Human Microbiome Project, which has generated a 2.3 terabyte 16s ribosomal RNA metagenomics data across 15 body sites. 3

The microbiome is important for the development, nutrition and immunity of human. Bacteria populating within our body could be beneficial. Diseases such as muscular dystrophy, fibromyalgia and diabetes are caused by the dysfunction of the microbiome.   





Factors that affect the composition of microbiome:


Host genetics

The microbiota of human with varying genetic relationship (parents, children and monozygotic twins) were analyzed using DNA-based fingerprint to conclude that host genotype has a noticeable influence on the composition of dominant bacteria, where the microbiota of monozygotic twins had the highest similarity. 4 It is difficult to state the host genotype-microbiota interactions in human as there will be other environmental or maternal factors that will influence the structure of microbiota. To avoid such influence, genetically inbred lines of animal and specific knock out mice are used. 56 In order to reflect the genetic diversity of human, 8 recombinant inbred strains were investigated using ARISA-based fingerprinting method 7. This study concluded that the background of genetic could significantly change the microbiota composition. In another study, Apoe-I knockout mice with damaged glucose tolerance were used to investigate

The relationship between host genetic and metabolic syndrome. The 16S rRNA genes were pyrosequenced and the result showed that 12% of the total structural changes of microbiota in the gut were contributed by the Apoe-I mutation. 8 These studies argue that host genetics could have an impact on the composition of gut microbiota, even a single gene mutation could cause the microbiota undergoes structural alternations.



Method of childbirth

The way how human is born- either vaginally or via C-section will have an impact on the bacterial communities within our body. Those born vaginally would be colonized by maternal faecal and vaginal bacteria. The vaginal microbiota has a low diversity, example bacteria would be Bifidobacterium, Lactobacillus and Enterobacteriacea, where Enterobacteriaceae is the most likely bacterial group that is through direct transmission from mother to children by faecal contact.9 In the first few days after birth, a relatively high numbers of lactobacilli could be found in the gut of infant and vaginal microbiota is mostly composed of lactobacillus.10 In a recent study, another bacterium Bacteroides has also been suggested to be transmitted during or after vaginally delivery.11 By pyrosequencing of 16s RNA genes, the intestinal microbiota of vaginally delivered neonates is found to be shared a much higher similarity sequence with their mother than with other mothers, because these intestinal microbes normally don’t populate outside the gut, it is very likely that it is transmitted between human hosts.12 Infant born by C-section don’t have faecal or vaginal contact with the mother, so they are colonized with microbes associated with operating room environment or skin. Therefore, C-section delivered neonates may have a delayed colonization or lack of one of the essential gut phylum. Bacteroidete-a bacterium which is especially good at degrading high-molecular-weight organic matter, its colonization is delayed by C-section delivery. 13 Microbial stimulation is required for more balanced immune phenotype, e.g. the development of regulatory T cells response. 14 In recent studies, it has been suggested that the diversity of microbiota would be lower with C-section than by vaginally delivery.


Maternal diabetes status

Interestingly, not only the mode of delivery, the maternal diabetes status also has an impact on the bacterial communities in our body. A recent study assessed the meconium and faecal samples collected from 23 preterm infants differed by maternal diabetes status by multi-barcode 16s rRNA gene sequencing technique. As figure 1 shown, there is a significant difference (p<0.05) of the family, class, phylum level between healthy, type 2 diabetes and gestational diabetes groups. From the figure, group with type 2 diabetes shows a significant enrichment of Bacteroidetes (phyla) and Parabacteriodes (genus). 15