The forgotten organ – Human microbiota

December 11, 2018, 9:49 341

Studies of the diversity of the human microbiome started in 1680s with Antonie van Leewenhoek, who had compared his oral and fecal microbiota. He noted the striking differences in microbes between these two habitats and also between samples from individuals in states of health and disease in both of these sites.

What is the human microbiota?

It has been known for a long time that humans harbor a microbial ecosystem, known as human microbiota, remarkably dense and diverse, made up of a number of viruses and cells much higher  than those of the human body, and that accounts for one to three percent of body weight. All the genes encoded by the human body’s microbial ecosystem, which are about 1000 times more numerous than those of our genome, make up the human microbiome. Microorganisms colonize all the surfaces of the body that are exposed to the environment.  Indeed, distinct microbial communities are found on the skin, in the vagina, in the respiratory tract, and long the whole intestinal tract.




The human gut microbiota


The largest microbial community of the human microbiome is located in the digestive tract, and more precisely in the large intestine. It is estimated to harbor approximately 104 bacterial cells and more than a 100 times the number of genes of the human genome. The diversity among the microbiome of individuals is immense compared to genomic variation: individual humans are about 99.9% identical to one another in terms of their host genome, but can be 80-90% different from one another in terms of the microbiome of their hand or gut.

The genetic diversity found within human gut microbiota allows to digest compounds via metabolic pathways not explicitly coded for in the mammalian genome, increasing the ability to extract energy from diverse diets.  As such, it plays a very important part in the host’s life, being closely interconnected to its health.

Starting from the birth, the gut microbiota has three essential roles: protective, metabolic, and trophic. First, gut microorganisms serve as a barrier against the proliferation of pathogenic organisms. Second, they play an important role in: the digestion and metabolism of colostrum, breast milk, formula, and weaning foods in infants, and a wide variety of food in adults; the breakdown of toxins and drugs; vitamin synthesis; and ion absorption. Trophic functions include the growth and differentiation of the epithelial cells lining the intestinal lumen, and the homeostatic maintenance of the immune system including tolerance to food antigens.

Changes in its composition can contribute to the development of obesity and metabolic syndrome. Human gut microbiota protects against the development of type I diabetes. Many diseases, both in children and adults, such as stomach cancer, lymphoma of mucosa-associated lymphoid tissue, necrotizing enterocolitis (an important cause of morbidity and mortality in premature babies) or chronic intestinal diseases, are, and others seem to be, related to the gut microbiota.

Prenatal influences on the development of the gut microbiota


Maternal microbiome during pregnancy


Pregnancy affects all body systems, including maternal microbiome. Gestational changes in the vaginal and intestinal microbiome are of particular relevance because these body sites are responsible for vertical microbial transmission to the newborn during vaginal delivery. The composition of the vaginal microbiota changes throughout the course of pregnancy.

The implications of the maternal gut and vaginal microbiota changes for the health of the mother and her offspring are unclear, but gestational changes in the vaginal and fecal microbiota are likely to be part of an adaptive response to protect and promote the health of the fetus and provide the newborn with a specific microbial inoculum at birth, before exposure to other environmental microbes. It is worth nothing that the composition of the microbial communities in the maternal gut and vagina are not independent of each other.

The intrauterine environment during healthy pregnancy has been presumed to be free of bacteria, although recent evidence of microbes present in the amniotic fluid, umbilical cord blood, fetal membrane, and placenta of healthy term pregnancies after both vaginal and C-section delivery has challenged this belief.

External factors during pregnancy such as drugs, illness, stress, or heavy metal exposure are known to influence the future development and behavior of the infant.  Few studies have been conducted so far to determine the impact of these factors on the microbial gut colonization of the infant. In animal trials, infant monkeys born from mothers stressed during pregnancy had significantly lower counts of Bifidobacterium and Lactobacillus when compared with control infants, born from non-stressed mothers. A study on a large cohort of human infants at 1 month of age showed that the use of antibiotics and/or probiotics by pregnant mothers had no effect on the fecal microbiota of infants. Overall, it seems that external factors can influence the establishment of the intestinal microbiota of infants, although at a low level.


Normal development of the infant’s intestinal microbiota


The intestinal microbiota of infants is very different from the one of adults and shows very important interindividual variability. Similarities appear around 1 year of age and converge towards a more commonly shared adult-like microbiota.

The succession of bacterial species in the first months of life is very complex. It involves many transient species that will disappear once the conditions of the gut have changed, but also species that will be present during the adult life. Although the time frame and bacterial species involved in the normal development of the intestinal flora of the infant is fairly well understood, the parameters influencing it are more difficult to comprehend.

It is becoming evident that initial microbial colonization and the resulting immune and metabolic programming have a long-lasting influence on the risk for diseases. For example, cesarean section delivery seems to increase the risk of celiac disease, type 1 diabetes, and asthma, which is generally associated with excessive or aberrant T-helper responses. Three weeks after birth, the bacterial cellular fatty acid profile in fecal samples differs significantly between infants developing atopy and those not. Furthermore, lower numbers of Bifidobacterium during early infancy (6 and 12 months) correlated with being overweight and obesity when infants reached 7 years of age.


Extrinsic influences on the development of the gut microbiota


Influences of the mother


The mother probably represents the most influential external factor for the development of the infant’s microbiome, due to intimate contacts during birth, nursing, and early feeding.

Mode of delivery (vaginally or by C-section) has been demonstrated to have a strong influence on early gut colonization particularly on the number of Bifidobacterium. Analysis of the meconium of newborn infants by pyrosequencing revealed a strong correlation between the first microbial communities of the digestive tract and the microbial communities of either  the mother’s vagina (Lactobacillus, Prevotella, or Sneathia) in the case of vaginal delivery or the mother’s skin (Staphylococcus, Corynebacterium, and Propionibacterium) in the case of cesarean section.

Apart from the delivery mode, another strong influence in the development of the infant intestinal microbiota is the mode of feeding. Genotyping of bacterial isolates (Lactobacillus, Staphylococcus, and Bifidobacterium) from the breast milk of mothers and fecal samples of their infants revealed the presence of identical strains, suggesting an important role of breast milk as a source of early gut colonization in infants. The human breast milk is an important source of oligosaccharides, which have a strong prebiotic effect for the neonate’s developing microbiota.



Environmental influences

Apart from the mother, the familial environment has also been described as a strong influencing factor in the development of the intestinal microbiota. For example, infants with older siblings have lower total counts of bacteria per gram of feces, but a comparatively greater proportion of Bifidobacterium. All these sources of variation are also strongly influenced by geographical locations and cultural traditions.

The mother as well as cultural and geographical factors have a tremendous influence on the development of the intestinal microbiota in infants. The familial environment is a major source of bacteria that will colonize the gut during the first year of life.


                                                                                                                                                                                                                                               by  Mehdiyeva B.