The human microbiome begins forming at birth then steadily evolves during an individual’s lifetime. Different areas of the body have their own individual microbial profiles. A child’s microbiome reaches a stable configuration at around 2-3 years of age, with its species and strain composition generally maintained throughout the individual’s life. However, although there tends to be relative stability within individuals, the composition of any one person’s microbiome is likely to differ substantially from any other’s. Genetics may play a part in the microbiome’s development, since a study of monozygotic twins showed that twins’ microbiomes resemble each other to a significantly greater degree than those of pairs of unrelated individuals.
1. Reductions in NOD-like receptors increase presence of commensal bacteria
Human tissue cells have the ability to sense molecules which may threaten infection. They do so through pattern recognition receptors expressed in a cell’s cytosol (intra-cellular fluid), known as nucleotide-binding oligomerization domain receptors, in short NOD-like receptors (NLRs). NLRs play an essential role in controlling the intestine’s commensal bacteria, so an NLR deficiency can cause an increasing abundance of normally helpful microbes, resulting in a disequilibrium and a reduced capacity to eliminate newly colonizing bacteria. This is because NLRs regulate the bactericidal (bacteria destroying) ability of antimicrobial peptides secreted by the ileal crypt (a kind of ‘pocket’ in the wall of the small intestine) affecting microbiota composition and abundance. Several studies suggest that mutations of a type of NOD called NOD2, a protein coding gene associated with Crohn’s disease and Inflammatory bowel disease, can affect the interaction between host and microbiome through changes in antimicrobial activity.
2. Immunomodulation leads to microbiome change
Microorganisms involved in inflammatory disease are capable of modulating the immune system’s response to their presence, allowing them to either establish or consolidate an infection. Either as a result of this process (known as immunomodulation) or through immunodeficiency, the composition of the microbiome can change, reciprocally influencing the disease process. Many examples of this are known, including graft-versus-host disease (a condition occurring when donor bone marrow or stem cells attack the recipient), problems in kidney transplantation, hepatitis, cirrhosis, psoriasis, Inflammatory bowel disease, and arthritis. Furthermore immunosuppressive drugs, used to prevent a recipient’s body from rejecting a transplant, generally affect the microbiome-immune system balance.
3. Changing gene expression correlates with microbial diversity
Variations in a host’s gene expression have been found to correlate with changes in taxa distribution (microbial diversity) in the host’s microbiome. For example, differences in the expression of the lactase enzyme had a resultant impact on the abundance of Bifidobacteria in the gastrointestinal tract, probably since some bacterial strains appear to prefer lactose to glucose. In another case, enrichment of genes involved in the leptin-signaling pathway correlated with changes in the microbiota found in the nose, oral cavity, and skin. Leptin is a hormone which is among the best known markers for obesity, and the associated microbiome changes involved, for example, changing levels of: Veillonella (found in the anterior nares, the external part of the nostrils); Lachnospiraceae, and Haemophilus (located in the attached keratinized gingiva, part of the gum); Clostridium (in the right antecubital fossa, the part of the arm inside the elbow); Bacteroides (behind the ear); and Propionibacterium (in subgingival plaque, dental plaque formed under the gums).
Host genetic variation impacts microbiome composition across human body sites.
Ran Blekhman, Julia K. Goodrich, Katherine Huang, Qi Sun, Robert Bukowski, Jordana T. Bell, Timothy D. Spector, Alon Keinan, Ruth E. Ley, Dirk Gevers, and Andrew G. Clark.
Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome.
Maayan Levy, Christoph A. Thaiss, and Eran Elinav.
Host genetic architecture and the landscape of microbiome composition: humans weigh in.
Andrew K Benson.
Written and researched by: Francisco & Daniel of the Data Science Team