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the effect of gut bacteria on the brain


      I.            Gut bacteria
humans are considered sterile during pregnancy period. But during and after birth, they become an important place for many microorganisms that are found mostly in the mouth, skin, gut and urogenital tract body surfaces (Morgan,2012).human gut consists of more than 1013  to 1014 microorganisms which is more than 10 times the number of human body cell  and containing 150 times as many genes as our genome (Cryan and Dinan, 2012). Therefore, the gut flora is referred to as the forgotten organ (Cryan and Dinan, 2012).
II.1. Composition
The microbial composition of the gut microbiota varies across the digestive tract. In the stomach and small intestine, relatively few species of bacteria are generally present.  Over 99% of the bacteria in the gut are anaerobes, but in the cecum, aerobic bacteria reach high densities. (Hogenova, 2005).
The gut of an individual contains around 300- 500 species of bacteria. The upper tract, i.e., the stomach and the small intestine, contain few bacteria adhering to the epithelia because of the luminal medium containing acids, bile and pancreatic secretions which kill most of the microorganisms and because of the propulsive movements. However, even under these conditions, small numbers of bacteria (less than 103/g) are attached to gastric epithelia or present in mucus, among them is the Gram-negative Helicobacter pylori,104 are present in jejunum and 107 - 109/g are present in the ileum (Hogenova, 2005). On the other hand, the large intestine contains a diverse microbial ecosystem with high density of bacterial cells (1011- 1012/g) where anaerobic bacteria outnumber aerobes by a factor of 100 to 1000 fold. The variation of microbial numbers and composition across the length of the gastrointestinal tract is illustrated in Figure 1.


Figure 1: The variation of microbial numbers and composition across the length of the gastrointestinal tract. (Pandeya, 2012).

Factors shaping the GI microbiota
The microbiota composition is subject to shaping by host and environmental selective pressures (Juge and Thursby, 2017). To protect from injury and maintain homeostasis, the GI tract limits exposure of the host immune system to the microbiota by recruitment of a multifactorial and dynamic intestinal barrier (Juge and Thursby, 2017). The barrier comprises several integrated components including physical (the epithelial and mucus layers), biochemical (enzymes and antimicrobial proteins) and immunological (IgA and epithelia-associated immune cells) factors. An individual microbe's longevity is determined by whether it is contributing to the range of essential functions on which host fitness relies (Juge and Thursby, 2017) . It is proposed that organisms who do not contribute beneficial functions are controlled by, and may occasionally be purged during, for example, transferral of the microbiota to a new host (Juge and Thursby, 2017).

II.2. obtaining the Gut Flora
Multiple factors contribute to the establishment of the human gut microbiota during infancy (Juge and Thursby, 2017). The development and formation of the gut flora start immediately at birth and continue for two years.  More specifically, the human gastrointestinal tract (GIT) changes from being initially sterile, to possessing an adult-like stable microbiome by the time the infant reaches 2 years of age (Fouhy, 2012)  .
Many factors including (mode of delivery, feeding regime, maternal diet/weight) play an important role in the development of the gut microbiota and impact on the unique composition that each individual develops.  Other factors are shown in (figure: 2)


Figure 2 : Factors contributing to changes in gut microbiota composition in the first 2 years of life (Fouhy, 2012).

II.2.1. Mode of Delivery
Intestinal microbiota development begins immediately following birth. The composition of the infant’s evolving microbiota is initially defined by the mother, the source of the   newborn’s first microbial inoculum. Colonizing bacteria rapidly adapt to breast milk and epithelial mucins as sources of nutrients ( Salminen, et al, 2004).
The prevalence of caesarean section delivery in Western countries is increasing. Caesarean born babies are deprived of contact with the maternal/vaginal microbiota and the first exposure is characterized by a lack of strict anaerobes and the presence of facultative anaerobes such as Clostridium species. Caesarean born infants have a more slowly diversifying microbiota, with differences reported from normally born infants, even after six months of age ( Salminen, et al, 2004).
The sources of the bacteria that are first to arrive into the gut of naturally delivered newborns are believed to be the vagina, skin, and feces of the mother, which provide a mix of intestinal and non-intestinal species (Morelli, 2014).whereas the guts of Cesarean delivered babies are first inhabited by bacteria coming from equipment, air, other infants and nursing staff (Morelli, 2014).
A recent study found that there was a strong vertical transmission of vaginal microbes from the mother to the infant when birth was by vaginal delivery, resulting in a dominant number of Lactobacilli and Bifidobacteria within hours of birth, whereas the gut of caesarean delivered infants contained maternal skin microbes, with Staphylococci being dominant (Fouhy, 2012).
Maternal skin and vaginal strains colonize only transiently, and the infant continues to acquire microbes from distinct maternal sources after birth ( Ferretti ,2018).

Figure 3 : mother to infant micro bacteria.     
II.2.2. feeding regime

The early feeding mode, i.e., breast feeding or system feeding has an affect on the composition of the infant’s gut flora. Breast feeding is known to be advisable on different levels. In addition to being a distinctly nutritious food, breast milk can affect the gut flora composition by containing prebiotics, lactoferrin (an antimicrobial protein) and lysozyme (Fouhy, 2012). It additionally carries around 109 microbes/L such as distinctive types of bacteria: Staphylococci, Streptococci, Corynebacterium, Lactobacilli, Micrococci, Propionibacterium, and Bifidobacterium which originate from the area around the nipples and the milk ducts, and a current study suggests that breast milk may also include Lactobacilli (Morelli, 2014). As a result, the guts of breast   fed kiddies comprise higher Bifidobacteria degrees in contrast with artificial milk fed babies, whereas the artificial fed babies includes greater levels of E. coli and clostridia species (Fouhy, 2012).
eating a solid food  affects the composition of the intestine microbiome. A study proved  that the introduction of solid meals used to be associated with an amplify in Bacteroidetes and Firmicutes and it recommended that through 2.5
Years the intestine microbiota carefully resembles that of an  old individuals  (Fouhy, 2012).

II.2.3. Maternal Weight
Obesity is considered a global epidemic. Specifically, obesity during pregnancy programs an increased risk of the offspring developing metabolic disorders in addition to the adverse effects on the mother per se. Large numbers of human and animal studies have demonstrated that the gut microbiota plays a pivotal role in obesity and metabolic diseases. Similarly, maternal obesity during pregnancy is associated with alterations in the composition and diversity of the intestine microbial community (Xiao and Zhou, 2018).
A study that examined participants at birth, at 3, 6, 12, 18 and 24 months and again when aged 4 and 7 years showed that infants of overweight mothers tended to be overweight or heavier at birth than those of normal weight mothers and also revealed that children who were classified as being of normal weight had, and continued to have, higher levels of Bifidobacteria and lower levels of Staphylococcus aureus than those who were obese (Fouhy, 2012).


References
1. Al-Asmakh, M., Anuar, F., Zadjali, F., Rafter, J., & Pettersson, S. (2012). Gut microbial communities modulating brain development and function. Gut microbes, 3(4), 366.
2. Bercik, P., Collins, S. M., & Verdu, E. F. (2012). Microbes and the gutbrain axis. Neurogastroenterology & Motility, 24(5), 405-413.
3. Bienenstock, J., & Collins, S. (2010). 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Psychoneuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms.Clinical & Experimental Immunology, 160(1), 85-91.
4. Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J. & Cryan, J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050-16055.
5. Collins, S. M., Surette, M., & Bercik, P. (2012). The interplay between the intestinal microbiota and the brain. Nature Reviews Microbiology, 10(11), 735-742.
6. Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701-712.
7. Cryan, J. F., & O‟Mahony, S. M. (2011). The microbiomegutbrain axis: from bowel to behavior. Neurogastroenterology & Motility, 23(3), 187-192.
8. De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G. & Lionetti, P. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences, 107(33), 14691-14696.
9. Foster, J. A. (2013, July). Gut Feelings: Bacteria and the Brain. In Cerebrum: the Dana forum on brain science (Vol. 2013). Dana Foundation.




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