The microbiome in the gastrointestinal tract has multiple influences on human health

Health maintenance and disease avoidance are important aspects of an active and productive life. It has become evident in recent years that a major factor in maintaining optimal health depends on the proper functioning of our complex gastrointestinal system. Unfortunately, gastrointestinal disorders are very common and range from simple digestive disorders to serious, life-threatening diseases.

Our gastrointestinal health is very much influenced by the microbiome, which is the population of micro-organisms which colonize the gastrointestinal tract. This means that managing the microbiome is crucial for health maintenance and disease avoidance.

Gastrointestinal microbiome

The microbiome is an enormous population of various micro- organisms which are predominantly bacteria. The size of the microbiome is not easy to estimate but it is generally considered that there are more microbial cells in our gastrointestinal tract then there are human cells in our body. Some of the most commonly found genera of bacteria in the microbiome of adults are; Bifidobacterium, Lactobacillus, Bacteroides, Clostridium, Escherichia, Streptococcus and Ruminococcus.

The composition of the gastrointestinal microbiome is not fixed but is dynamic and affected by numerous factors including birth conditions, early feeding, gastrointestinal tract infections, genetics, age, stress, medication and diet.

The microbiome produces a vast range of products. Fermentation of fibre and protein by bacteria in the large bowel produces short chain fatty acids, acetate, propionate and butyrate, which act as key sources of energy for colorectal tissues and maintain tissue integrity. Short chain fatty acids are also absorbed into the bloodstream and impact immune function and inflammation. Bifidobacterium generate vitamins such as K, B12, Biotin and Folate. The microbiome produces many enzymes which help to digest food materials.

An important characteristic of the microbiome is that it varies greatly among individuals. It has much greater variation than the genetic variation of the body. Individual humans are about 99.9% identical to one another in terms of their basic genetics. However, the microbiome can be 80-90% different from one individual to another. This suggest that exploiting the variation contained within the microbiome could be a much better approach to personalized medicine than exploiting the relatively constant human genetic make-up.

Development of the microbiome

It is important that a bene cial microbiome is rapidly established in the young infant soon after birth. The initial development of the microbiome depends upon the birth conditions. Infants born vaginally have a microbiome very similar to that of their mother’s vaginal and faecal micro ora. In contrast, the microbiome of an infant born by caesarean section comprises bacteria transferred horizontally from the mother’s and others’ skin surfaces and, to a lesser extent, the place of birth.

These differences in initial new-born microbiomes may have important health consequences. The microbiome in vaginally-born infants rapidly develops a good population of Bifidobacterium and Lactobacillus which are considered to be health protective. The microbiome of infants born by caesarean section frequently have high populations of Staphylococcus and Clostridium spp. which can be pathogenic. Thus, delivery mode appears to be an important factor in
the development of the infant microbiome, since surgically delivered infants miss the unique opportunity to be inoculated with their mother’s vaginal microbiome via the birth canal.

The microbiome starts to assemble immediately after birth, and during the first year of life, the infant diet is one of the most important factors that shape the microbiome. The influence of diet on microbiome development is clearly illustrated in infants with different feeding routines, namely breast milk feeding and formula feeding. Breast milk feeding promotes infant health by guiding the proper assembly and activity of the gut microbiome.

The benefit of breast feeding is related to the quality of human milk which contains proteins, fats, carbohydrates and various immunoglobulins. In particular, the carbohydrate fraction of human milk contains an important quantity of special oligosaccharides, known as human milk oligosaccharides (HMO).

Infants lack the enzymes necessary to digest HMO so most reach the colon unmodified where they can influence the development of the microbiome. These HMOs selectively stimulate the development of a Bifidobacterium-rich and Bacteriodes-rich microbiome which is health promoting.

On the other hand, formula-fed infants exhibit a microbiome with the presence of species of Staphylococcus, anaerobic Streptococcus, and Clostridium in addition to Bifidobacterium which is not so beneficial. Recently, milk formulas have been improved, notably by the inclusion of some HMO, which makes it possible for a formula-fed infant to establish a Bifidobacterium-rich microbiome.

In childhood the microbiome develops into the adult form and is relatively stable from 20 to 75 years old. In elderly people the microbiome changes and the Bifidobacteria decrease.

Impact of diet on the microbiome

Diet exerts a profound effect on the profile of the microbiome and therefore, it is important that an appropriate diet is available throughout life to ensure adequate development and maintenance of the microbiome.

This is another and possibly neglected aspect of human nutrition. Generally good nutrition is directed towards fulfilling requirements for protein, energy, vitamins and minerals in terms of growth of the body. However, nutrition also now needs to be directed towards efficient management of the microbiome as this has an overriding effect upon health maintenance and disease avoidance. Some nutrients such as HMO for example are not utilised for growth of the body but play an important role in establishing an effective microbiome. In the future we need to ensure that nutrition supplies nutrients for the human body and also supplies nutrients for the microbiome.

Short-term consumption of diets composed entirely of animal or plant products rapidly alter the microbiome. A diet based on foods of animal origin increases the abundance of bile- tolerant micro-organisms (Alistipes, Bilophila and Bacteroides) and decreases the levels of Firmicutes that metabolize dietary plant polysaccharides. These results demonstrated that the microbiome rapidly responds to an altered diet.

Functions of the microbiome

Starting from birth the microbiome is of fundamental importance for health because it helps in maintaining stable conditions in the gastrointestinal tract. It serves as a barrier against the proliferation of pathogenic micro-organisms. It plays an important role in the digestion and metabolism of various food materials. It is also active in the breakdown of toxins and drugs and in vitamin synthesis. The microbiome produces metabolites such as short-chain fatty acids and is important in maintaining the immune system.

Numerous diseases in both adults and infants have links to the microbiome, including, mucosa associated lymphoid tissue lymphoma, inflammatory bowel disease, obesity, necrotizing enterocolitis and cancer.

However, it is now evident that the microbiome not only influences events in the gastrointestinal tract but also has a long-distance effect exerting an influence remote from the gastrointestinal tract as far as the brain. This has given rise to the term “microbiota-gut-brain” axis. This concept attributes functions to the microbiome to modulate brain plasticity and influence early development of normal social and cognitive behaviours such as learning and memory.

Another important function of the microbiome may be in cancer therapy. Bacteria are known to modulate the anti-tumour efficacy of various chemotherapeutic and immunotherapeutic agents. There may well be a therapeutic advantage in modulating the microbiome of patients receiving an anti-cancer immunotherapy.

Characteristics of a healthy microbiome

An important parameter of a healthy microbiome is to maintain a stable system. Stability is the ability of the microbiome to resist change in response to stress and to return to an equilibrium state following a stress-related disturbance.

For example, a healthy microbiome has the ability to resist disturbances due to the entry of a pathogen, alteration of the diet, or administration of medication such as antibiotics and to return to a healthy state afterwards. The ability of the human microbiome to remain stable in the face of continuous and potentially disruptive perturbations is important for health maintenance and disease avoidance.

High diversity of the population in the microbiome has also been generally associated with good health. Conversely, a relative lack of diversity is apparent in the microbiome in diseases ranging from obesity to inflammatory bowel disease and types 1 and 2 diabetes.

If the universal features of the healthy microbiome could be de ned, then the absence of any features would be a useful predictor of the beginning of a disease. This would make it possible to determine the appropriate interventions to restore health, ranging from dietary or lifestyle changes through prebiotics, probiotics or pharmaceutical drugs.

Conclusions

The microbiome is a very large population of micro-organisms located in the gastrointestinal tract, predominantly in the colon. The number of bacteria in the microbiome is probably greater than the total number of cells in the body and plays an important role in health maintenance and disease avoidance.

Dietary components such as protein, fats, digestible and non-digestible carbohydrates, prebiotics, and polyphenols all induce shifts in the microbiome. The close relationship between diet, the microbiome, and health suggests that dietary modulation of the microbiome may guide the formation of health promoting microbiomes that could then be maintained throughout the lifespan. Therefore, nutrition also now needs to be directed towards efficient management of the microbiome. In the future we need to consider nutrition as a supply of nutrients for the human body and also as a supply of nutrients for the microbiome. It is well established that an optimal functioning of the microbiome will make a major improvement in health maintenance and disease avoidance and thereby improve our quality of life.

References

  • Jobin, C. (2018). Precision medicine using microbiota. Intestinal microbiota influence cancer patient response to immunotherapy. Science, 369: 32-43.
  • Lawrence, K. and Hyde, J. (2017). Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing. PLoS One, 12: e0179017.
  • Le Blanc, J.G., Milani, C., de Giori, G.S., Sesma, F., van Sinderen, D. and Ventura, M. (2013). Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Current Opinion in Biotechnology, 24: 160–168.
  • Sender, R., Fuchs, S. and Milo, R. (2016). Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell, 164: 337-340.
  • Thomson, P. and Garrido, D. (2017). Human milk oligosaccharides and health promotion through the gut microbiome. in: Dairy in Human Health and Disease Across the Lifespan. eds: Watson, R. R., Collier, R. J. and. Preedy, V. R. pp. 73-86. Academic Press.
  • Yang, I., Corwin, E. J., Brennan, P. A., Jordan, S., Murphy, J. R. and Dunlop, A. (2016). The infant microbiome: implications for infant health and neurocognitive development. Nursing Research, 65: 76–88.
  • Zivkovic, A. M., German, J. B., Lebrilla, C. B., and. Mills,
    D. A. (2011). Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proceedings of the National Academy of Sciences, 108: 4653–4658.

Article written by Dr. Clifford Adams

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