Keystone: Microbiome in Health and Disease

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by Dr. Matthew A. Roberts, Ph.D., MBA,  Chief Scientific Officer – KGK Science USA

 

The human microbiota is a complex ecosystem living with its host and is responsive to the human condition capturing information on lifestyle, exposure to environmental factors, and our association with other humans as well as pets.

We recently attended the Microbiome in Health and Disease Symposium, organized by Julie A. Segre, Ramnik Xavier and William Michael Dunne from Feb 5th to 9th at Keystone, Colorado. The symposium brought together experts in clinical medicine, clinical microbiology, microbial genomics, bacterial genetics, and genomic analysis to explore how both strain variation and the underlying microbial community determine health and disease.

Some highlights from the meeting included Prof. Rob Knight from the Centre for Microbiome Innovation – University of California, San Diego.  He explained that while we may share 99.99% similarity with one another at the genetic level, we may only share 10% similarity across our microbiome. Providing insight into the observed variability in responses to diet, allergy, disease and environmental interactions. Furthermore, Prof. Knight predicts the rise of personalized mouse models that harbor an individual’s microbiome, where the effect of interventions, be it antibiotics or therapeutics against chronic and acute diseases, may be tested for its efficacy prior to therapy (see also   ‘Defining the Microbiome’, Ursell et al, Nutr Rev. 2012 August ; 70 (Suppl 1): S38–S44). From this authors view point, advances in these mouse models may also help unravel a responder vs. non-responder population where nutrition and dietary supplements are likely to have a significant effect compared to the placebo. That may one day lead to a personalized dietary supplementation approach to optimize a healthy microbiome.

The complexity of the human microbiome is a result of interactions between environment, genetics, microbiota and the innate immune system, and cannot be deciphered by simply deconstructing this second genome into its individual parts. Bob Hancock  from University of British Columbia, Canada, described a high throughput approach to analyzing genomic information using protein-protein interaction networks as an emerging area of science called network biology. Adapting computational methods to network biology resulted in the development of InnateDB and NetworkAnalyst  a high throughput meta-analysis and network analysis tool that can be applied to transcriptomic, proteomic, metabolomic and epigenetic data generating insights into host response to infections, inflammatory and chronic diseases and in identifying nutritional regulation of the innate immune system.

 

Sarkis Mazmanian from CalTech, USA presented a fascinating prospect for ameliorating diseases of the nervous system through unraveling the Gut-Microbiome-Brain connection. Though demonstrated in a mouse model, it holds potential in Parkinson’s Disease as the associated neuropathology is thought to be a result of abnormal postnatal signaling between the gut and the brain. Recolonizing the gut of a mouse with microbiota from patients suffering from Parkinson’s showed that the disease was now transferred to the mouse. Such studies on gut-brain cross talk have revealed fascinating insights linking a complex network of interactions modulating the gut and the emotional and cognitive centers of the brain with other functions such as immune activation, intestinal permeability and entero-endocrine signaling. From this authors view perspective, the Gut-Microbiome-Brain connection is a fluid entity subject to change due to alterations in the microbiome. This presents many opportunities for dietary and lifestyle interventions to optimize a healthy microbiome as we learn more about the complex microbial community that is so important to health & disease.

Moving Forward With Dietary Supplements

New genomic & molecular assessment technologies, capable of capturing a snapshot of this rich biological interaction, are now available to the scientific community. These analytical tools have generated considerable insights into the host’s response to infections, inflammatory and chronic diseases, and in identifying nutritional regulation of the innate immune system – especially through the use of pre- and pro-biotics. The latter is significant in identifying beneficial dietary supplements that may reverse gut dysbiosis towards a healthy eubiosis through host-microbe interaction mechanisms that can be captured using computational tools.

Certainly, designing clinical trials that capture the multifaceted effects of supplements as they influence these pathways of communication provides for opportunities to promote health. As well, identifying responder vs non-responder populations will aid in better clinical evaluation of the efficacy of dietary supplements, especially pre- and probiotics. Results from microbiome research, the knowledge we can gain from examining the interaction between diet, lifestyle, and the micro biome may also one-day lead to a personalized dietary supplementation approach to optimize a healthy microbiome.

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