How do microRNA or ORNs (oligoribonucleotides) effect your immune system?
Probiotics have had a long history in helping farmed animals combat gut disfunctions caused by overuse of antibiotics to stimulate faster growth. In the 1950s the readily available antibiotics gave rise to the concern that using it as a substance to promote growth was creating resistant populations of bacteria, which means that antibiotics would lose effectiveness against infections from bacteria. Although in 1969 antibiotics were restricted as a growth promotor, the use has not subsided until very recently with the rise of organic and grass-fed animal farms. Fuller (1989) noted that antibiotics have a long-lasting upsetting effect in the gut because of the imbalance caused in the indigenous gut flora. In today’s language, antibiotics disrupt the natural microbiome, causing various diseases (Langdon et al., 2016). Probiotics offer a practical solution as an alternative therapy. For example, they exert antimicrobial properties by inhibiting adhesion of pathogens to the mucosa (Salas-Jara et al., 2016; Chenoll et al., 2011), or produce bacteriocins lethal to the pathogens, as the supernatant is able to do (Reid & Burton, 2002)
MicroRNA Immune-Modulating: Bacteria release immune-modulating molecules when entering the mouth, such as ribonucleic acid or RNA, as though they are ready to defend themselves. Small pieces of RNA, called MicroRNA (miRNA) or oligoribonucleotides (ORNs), are released by pathogenic bacteria as well as a beneficial bacterium such as Lactobacillus casei, which we find in fermented foods like yogurts. Other lactobacillus organism occurs naturally in fruits and vegetables. Marshall (2010) tested L. Casei among other beneficial probiotics to assess their readiness to fight pathogenic organisms in case of invasion and found that these small pieces of RNA or ORNs control the expression of growth genes in the pathogen’s genomes. The probiotic bacteria grow faster after releasing the ORNs, mounting a better defense system to invading bacterial infections (Marshall, 2014).
MicroRNA (or ORNs) play important regulatory role in physiological processes in animals (and plants), and is studied for miRNA-based therapeutics (Wahid et al., 2010). miRNA regulate gene expression in all aspects of biology, with certain endogenous miRNAs participating in antiviral defense mechanisms, such as miR-32 with inhibitory effects against the retrovirus type 1 (PFV-1; similar to human immunodeficiency virus such as Epstein-Barr and others) and protects human cells from PFV-1 (Lecellier et al., 2005). Other studies, such as Ma et al. (2011) found another miRNA (miR-29) controlling innate and adaptive immune response to intracellular bacterial infection. With dysbiosis of the gut, inflammation hasten immunological imbalances, influencing the onset of many chronic illnesses, including cancer. The opposite is also a viable solution – maintaining the health of the microbiome (Cianci et al., 2019).
Lactobacillus acidophillus and Bifidobacterium bifidum regulate and modulate the GI-tract, increasing production of certain microRNA that improve colon cancer treatment (Heydari et al., 2018). From the GI-tract to the brain, Zhao et al. (2019) have shown that probiotics protect against inflammatory neurodegeneration caused by neurotoxins in the gut, contributing to a healthier brain function. Probiotics with their supernatant and microRNA or ORNs regulate and support a balanced function of the GI-tract. MicroRNA have emerged as major players in the interaction between host (human body) and bacterial pathogens, with an integral part in the host immune response to bacterial infection (Aguilar et al., 2019; Sunkavali et al., 2017).
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- Aguilar, C., Mano, M., & Eulalio, A. (2018). MicroRNAs at the Host–Bacteria Interface: Host Defense or Bacterial Offense. Trends in microbiology. Abstract
- Chenoll, E., Casinos, B., Bataller, E., Astals, P., Echevarría, J., Iglesias, J. R., ... & Genovés, S. (2011). Novel probiotic Bifidobacterium bifidum CECT 7366 strain active against the pathogenic bacterium Helicobacter pylori. Applied and environmental microbiology, 77(4), 1335-1343. DOI: 10.1128/AEM.0182-10
- Cianci, R., Franza, L., Schinzari, G., Rossi, E., Ianiro, G., Tortora, G., ... & Cammarota, G. (2019). The Interplay between Immunity and Microbiota at Intestinal Immunological Niche: The Case of Cancer. International journal of molecular sciences, 20(3), 501. Abstract
- Heydari, Z., Rahaie, M., Alizadeh, A. M., Agah, S., Khalighfard, S., & Bahmani, S. (2018). Effects of Lactobacillus acidophilus and Bifidobacterium bifidum Probiotics on the Expression of MicroRNAs 135b, 26b, 18a and 155, and Their Involving Genes in Mice Colon Cancer. Probiotics and antimicrobial proteins, 1-8. Abstract
- Langdon, A., Crook, N., & Dantas, G. (2016). The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome medicine, 8(1), 39. Article
- Marshall, W. E. (2010). Oligoribonucleotides alert the immune system of animals to the imminence of microbial infection. U.S. Patent No. 7,678,557. Washington, DC: U.S. Patent and Trademark Office. Article
- Salas-Jara, M. J., Ilabaca, A., Vega, M., & García, A. (2016). Biofilm forming Lactobacillus: new challenges for the development of probiotics. Microorganisms, 4(3), 35. doi:10.3390/microorganisms4030035
- Sunkavalli, U., Aguilar, C., Silva, R. J., Sharan, M., Cruz, A. R., Tawk, C., ... & Eulalio, A. (2017). Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia. PLoS pathogens, 13(4), e1006327. Abstract
- Reid, G., & Burton, J. (2002). Use of Lactobacillus to prevent infection by pathogenic bacteria. Microbes and infection, 4(3), 319-324. https://doi.org/10.1016/S1286-4579(02)01544-7
- Zhao, Y., & Lukiw, W. J. (2018). Microbiome-mediated upregulation of microRNA-146a in sporadic Alzheimer’s disease. Frontiers in neurology, 9, 145. Article
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