Harnessing the microbiome potential

Spring is underway in parts of the US, and while Florida by no means undergoes the dramatic reappearance of foliage or colorful clumps of daffodils and azaleas, the southern part of the sunshine state experiences its share of spring renewals.  For instance, recently a brood of Muscovy duck (Cairina moschata) hatchlings appeared near Ocean Ridge Biosciences' laboratory.  Actually the emergence of these chicks at the time of year that northern climates see increased animal birthrates is a coincidence as the Muscovy ducks, which are native to Mexico, Central and South America, generally breed three times a year. 

Interestingly, these ducks are characterizedMuscovy_Duck_Audubon_2400x1631 by what is called a “wattle” around their bills once they reach adulthood.  The wattle appears as gnarly red tumorous tissue, especially for males, and surprisingly, the hatchling phenotype is remarkably different from the mature organism. Not only is there an absence of any wattle, but the downy chicks and young ducks parading around ORB’s office were covered in striking tiny yellow feathers.  As these chicks matured into young ducks, my colleagues and I observed the hen and drake caring for their progeny.  Moreover, local homo sapiens also provided sustenance and protection to this ever-shrinking brood.  These observations prompted us to ponder if all nascent organisms are capable of evoking human kindness.  ORB scientists speculated that while humans' deliberate sharing of their resources seems to hold true for most organisms within the Kingdom Animalia, at least in theory, the idea unravels when applied to the Plantae Kingdom and outright falls apart with fungi and prokaryotes.  One exception to this idea that humans are not altruistic to fungus or unicellular organisms is the introduction of probiotics to help selected microorganisms proliferate.  

In the last five years, investigations of the gut microbiome have skyrocketed largely due to advances in the massively parallel sequencing technology and bioinformatic approaches such as the reconstruction of transcriptomes using de novo assembly in the absence of complete reference genomes.  These metatranscriptomic studies of stoolmicrobiome-therapies_800x504 samples have identified and cataloged bacteria, fungus, and viruses that are common to healthy colonic microbial populations.  For instance, over 35,000 bacterial species comprise the gut microbiota; although organisms belonging to the phyla Firmicutes and Bacteroidetes are predominate1.  The literature includes a substantial body of work associating the dysbiosis of the microbiome with many pathologies including metabolic diseases, colorectal cancer, multiple sclerosis, cognitive developmental disorders, and autoimmune diseases2-10.  There has been a wave of companies rushing to leverage these connections to develop novel therapeutics.  In fact, over 20 well-funded start-ups have recently surfaced.  Their missions are aimed at harnessing the power of the microbiome to treat and prevent disease.  Of these microorganisms-orientated companies, Vendanta Biosciences is tackling solid tumors with bacteria, Seres Therapeutics is optimizing fecal transplants to treat recurrent Clostridium difficile infections, and Blue Turtle Bio is also utilizing bacteria from the gut microbiome but as a drug delivery platform.  A Swedish company, Infant Bacterial Therapeutics (IBT), which is taking on necrotizing enterocolitis (NEC) with Lactobacillus reuteri-based candidates, has been granted the Rare Pediatric Disease Designation by the FDA for its lead drug candidate to prevent NEC – a disease which is fatal, especially for premature neonates.

The modulation of the gut microbiota composition of infants and children has been investigated as a therapeutic route for atopic dermatitis, bacterial gastroenteritis, inflammatory bowel disease, necrotizing enterocolitis, and allergic diseases11.  Probiotic interventions encourage the growth of commensal bacteria and ward off the colonization of pathogenic organisms, thereby affording protection to the intestinal barrier function and reducing food allergies and atopic diseaseInfant_332x318 incident rates12.  Infant formula containing low dose Bifidobacterium lactis supplementation is shown to provide similar early life outcomes to breastfeeding with regards to gastrointestinal infection rates and immune system and gut maturation13.  However, benefits of probiotic usage are not limited to infants. 

The Probiotics in Pregnancy Study conducted in Wellington and Auckland, New Zealand involved the administration of Lactobacillus rhamnosus four hundred pregnant women during pregnancy and breastfeeding.  This study showed reduced rates of infant eczema and atopic sensitization at 12 months but also decreased rates of material gestational diabetes mellitus and the presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus, and postpartum depression and anxiety14.

Although kindness is not the motivating factor behind probiotic supplementation, it’s undeniable that this is a promising strategic approach for drug discovery and development companies to treat infant, pediatric, and adult diseases.

References

  1. Jandhyala, S. M., Talukdar, R., Subramanyam, C., Vuyyuru, H., Sasikala, M., & Reddy, D. N. (2015). Role of the normal gut microbiota. World Journal of Gastroenterology: WJG, 21(29), 8787.
  2. Armougom, F., Henry, M., Vialettes, B., Raccah, D., & Raoult, D. (2009). Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PloS one, 4(9), e7125.
  3. Brown, C. T., Davis-Richardson, A. G., Giongo, A., Gano, K. A., Crabb, D. B., Mukherjee, N., & Hyöty, H. (2011). Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PloS one, 6(10), e25792.
  4. Larsen, N., Vogensen, F. K., van den Berg, F. W., Nielsen, D. S., Andreasen, A. S., Pedersen, B. K., & Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS one, 5(2), e9085.
  5. Weir, T. L., Manter, D. K., Sheflin, A. M., Barnett, B. A., Heuberger, A. L., & Ryan, E. P. (2013). Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PloS one, 8(8), e70803.
  6. Zhang, Y. J., Li, S., Gan, R. Y., Zhou, T., Xu, D. P., & Li, H. B. (2015). Impacts of gut bacteria on human health and diseases. International journal of molecular sciences, 16(4), 7493-7519.
  7. Jangi, S., Gandhi, R., Cox, L. M., Li, N., Von Glehn, F., Yan, R., & Cook, S. (2016). Alterations of the human gut microbiome in multiple sclerosis. Nature Communications, 7.
  8. Cao, X., Lin, P., Jiang, P., & Li, C. (2013). Characteristics of the gastrointestinal microbiome in children with autism spectrum disorder: a systematic review. Shanghai Arch Psychiatry, 25(6), 342-53.
  9. Lyte, M. (2013). Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior. PLoS Pathog, 9(11), e1003726.
  10. Brusca, S. B., Abramson, S. B., & Scher, J. U. (2014). Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Current opinion in rheumatology, 26(1), 101.
  11. Awasthi, S., Wilken, R., German, J. B., Mills, D. A., Lebrilla, C. B., Kim, K., & Maverakis, E. (2016). Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial. Trials, 17(1), 340.
  12. Cao, S., Feehley, T. J., & Nagler, C. R. (2014). The role of commensal bacteria in the regulation of sensitization to food allergens. FEBS letters, 588(22), 4258-4266.
  13. Baglatzi, L., Gavrili, S., Stamouli, K., Zachaki, S., Favre, L., Pecquet, S., & Costalos, C. (2016). Effect of infant formula containing a low dose of the probiotic Bifidobacterium lactis CNCM I-3446 on immune and gut functions in C-section delivered babies: a pilot study. Clinical medicine insights. Pediatrics, 10, 11.
  14. Barthow, C., Wickens, K., Stanley, T., Mitchell, E. A., Maude, R., Abels, P., & Hood, F. (2016). The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double-blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy. BMC pregnancy and childbirth, 16(1), 133.

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