Metabolon has the capacity to support Siolta Therapeutics through the complete research continuum focused on pediatric and early life microbial networks.
“Metabolomics, generally speaking, allows us to investigate a step further, moving from what potential is present to what functions are being fulfilled. This is a critical step in pushing the boundaries of our knowledge beyond who and what is present and moving towards functional characterization and finer resolution of metabolic networks.”
Siolta was co-founded in 2016 by Susan Lynch, Ph.D., (University of California at San Francisco, or UCSF) and Nikole Kimes, Ph.D., (Siolta, formerly UCSF) in partnership with Samir Kaul (Khosla Ventures). The clinical-stage biotech company is on a mission to alleviate the suffering of millions impacted by chronic inflammatory diseases through novel microbiome-based medicines. The company leverages its deep knowledge of the developing infant gut microbiome and its role in promoting immune tolerance to develop targeted microbial therapeutics and companion diagnostics for the prevention and treatment of inflammatory diseases.
The company was aptly named after the Gaelic word for “seeds” because their microbial therapeutics are reseeding the depleted gut microbiome with naturally occurring bacteria, essential for a healthy immune system.
The Siolta team chose to focus on early life because it is where the science has shown they can have the most transformative impact. “There is now substantial evidence that the developing microbiome is instrumental in establishing and maintaining healthy immune responses. Moreover, disruption to this process is thought to underlie a myriad of chronic diseases, including allergic, metabolic, and neurodevelopmental diseases; all of which are increasing in incidence at alarming rates in our children,” said Dr. Kimes. “This unique early-life window has the potential to be instrumental in approaching disease from an innovative prevention standpoint. We are developing a method where the underlying causes of chronic disease are addressed through early intervention, rather than treating downstream symptoms later in disease development. This has a lot of positive outcomes – lower costs, fewer side-effects and the potential to eliminate the long-term treatment modalities used for asthma and allergy sufferers today.”
Untargeted or global metabolomics coupled with targeted assay development
Siolta utilizes both untargeted and targeted metabolomic approaches to help characterize the overall metabolic signatures associated with treatment and response and potentially provide insight into patient stratification for more precise therapeutic approaches moving forward. They start with untargeted metabolomics, casting a wide net to characterize general metabolic shifts across different pathways and to identify the biomarkers that we may not know are there yet. Once the analysis is complete and they have pinpointed the biomarkers they want to focus on, they work to develop a targeted assay.
Dr. Kimes shared that earlier published work from Dr. Lynch’s lab examined how untargeted metabolomics has helped characterize early-life signatures of infants at risk for developing allergy and asthma. The work establishes that different microbial profiles are associated with different metabolic signatures, immunological impacts, and disease outcomes1,2. Furthermore, the approach was used to identify specific metabolites associated with high risk infants for allergy and asthma, as well as the associated microbial genes capable of producing such metabolites, that are capable of impeding immune tolerance3. Thus, Dr. Lynch’s work established a potential mechanistic link between early life microbiome perturbations and disease development later in life, while also identifying a potential biomarker for high risk infants.
The value of genomics and metabolomics, together
The genomic revolution that has occurred over the past few decades is fundamental to our current understanding of complex microbial communities, including the human microbiome. The resulting advancements in technology have led to increased awareness of the role microbial communities play in environmental and human health, including the vast functional potential harbored by these complex systems.
Metabolomics adds to the toolbox allowing Siolta to understand the complex associations between microbial activity in the hug and human health. “It provides another layer of analysis that allows us to more directly address the functional contribution of the microbiome to human physiology.” The study of metabolites has enabled the company to better characterize both general phenomena, through untargeted metabolomics, and more specific mechanisms of action, through targeted metabolite analysis. “Both of which are important drivers of research and development in this emerging field,” adds Dr. Kimes.
1. Fujimura KE, Sitarik AR, Havstad S, Lin DL, Levan S, Fadrosh D, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature Medicine. 2016Dec;22(10):1187–91.
2. Durack J, Kimes NE, Lin DL, Rauch M, Mckean M, Mccauley K, et al. Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation. Nature Communications. 2018;9(1).
3. Levan SR, Stamnes KA, Lin DL, Panzer AR, Fukui Eundefined, McCauley K, et al. Elevated faecal 12,13-diHOME concentration in neonates at high risk for asthma is produced by gut bacteria and impedes immune tolerance. Nature Microbiology. 2019Jul22;4:1851–61.