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New work shows gut microbial taxa might vary, but function is stable in people with Crohn’s disease in remission

The numbers, types, and functions of gut microbes and the molecules they produce vary greatly over time and between individuals; however, there is new evidence showing that the metabolic function these microbes perform is conserved in some cases. This new data comes from an analysis of the gut microbiome from several individuals with Crohn’s disease throughout a whole year. The study further showed that the conserved functions are redundant across multiple phyla in the gut microbiome and that gut microbiome metabolism is driven by a web of interconnected reactions and enzymes.

Research has revealed that the gut microbiome plays a fundamental role in our overall health. The microbiome is involved in several vital biological functions including, metabolism, digestion, and immunity. Scientists have shown that there is an enormous amount of variability in the species making up the gut microbiome of any one individual, and this variability is even greater in people with inflammatory bowel disease (e.g. Crohn’s disease).  This makes any investigation into why a microbiome is not functioning properly extremely difficult. To get around this, researchers posed the question of whether microbial composition was really the best way to seek answers.

The group carrying out this work included researchers from all over the US and included Microbiome Insights Scientific Advisory Board member Dr. Janet Jansson ofthe Pacific Northwest National Laboratory in Richland, Washington. Their approach was to focus on discrete “metabolic modules” within a gut microbiome instead of taxa or genetic relationships, the idea being that different bacteria can perform similar metabolic functions; so while two humans have a different make-up of species, their microbiomes on the whole could be functioning similarly. With this concept, the researchers wanted to tackle an open question in microbiome and inflammatory bowel disease (IBD) research—how does the observed volatility in the microbiome composition of patients with IBD influence the functions of the microbiome?

Fecal samples from individuals with Crohn’s following resection surgery and in remission were collected at 5 time points throughout a year and a dual metagenomics/metaproteomics approach applied: they used shotgun metagenomics sequencing to identify genes from the microbiome species and two-dimensional liquid chromatography tandem mass spectrometry to isolate the proteins. They found that the metaproteomes (the collections of proteins expressed by microbes in the samples) were highly personalized, meaning all the samples taken from an individual more closely resembled each other than they did any sample from another individual. There was, however, still a great deal of variability between the samples taken at different times from a single person. Next they identified “metabolic modules” of proteins known to be involved in certain pathways and functions. In doing so they observed that there were similar and redundant metabolic functions across the different phyla observed over time and between individuals. By further combing through the modules, a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products could be found.  According to the researchers, the modules show the interconnectedness of gut microbiome metabolism, meaning that the overall operation of the microbiome should be thought of as network focused on metabolic function.  

This study was not specifically designed to compare healthy vs. unhealthy individuals, says the research team, but because this population is known to have a wide range of taxonomic variability they were chosen to investigate how variation affects function. According to researchers, “the data revealed that microbiomes of these post-surgery individuals had significant variability in taxa, genes, and proteins; however, key metabolic modules associated with central metabolism were seen in all samples, even though the phyla of origin was often different.” Furthermore, they believe this approach provides a unique way to follow metabolic reactions and enzymes, even when the species and proteins involved vary. 

Blakeley-Ruiz JA, Erickson AR, Cantarel BL, et al. Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn’s remission patients despite temporal variations in microbial taxa, genomes, and proteomes. Microbiome. 2019; 7:18.

 

 

PRESS RELEASE: Rebiotix and Microbiome Insights collaborate on a microbiome IBD tool for clinical development

Recent study provides proof of concept for using novel scoring system to define IBD-related changes in microbiome

With a growing body of science linking gut microbiota to inflammatory bowel disease (IBD), a need exists in clinical settings to understand changes in the gut microbial community as they relate to IBD and its management.
Two leading microbiome companies, Rebiotix (part of the Ferring Pharmaceuticals Group) and Microbiome Insights, are collaborating to validate one such tool: a proprietary analysis to determine how closely a patient’s microbiome resembles that of someone with IBD. Microbiome Insights’ bioinformaticians developed an IBD Microbiome Score, based on a vast dataset of over 1600 individuals with IBD and healthy controls. The metric combines the latest understandings of the gut microbiome as a complex ecosystem with information on hundreds of taxa in the bacterial community, rather than the presence or absence of specific taxa. Based on fecal microbial characterization by sequencing, the IBD Microbiome Score can be assigned for each individual patient at diagnosis and at different times throughout treatment, making the Score practical for clinical use. Leveraging Rebiotix’s proprietary Microbiota Restoration Therapy™ (MRT) drug development platform, the Score is being evaluated in active clinical trials to treat IBD.

“The microbiome field is enormously complex,” says Dr. Ken Blount, Rebiotix’s Chief Scientific Officer. “With the use of the first-in-class Rebiotix MRT platform continuing to expand into complex conditions such as IBD, it is critical to have strong, scientifically-validated tools to understand the dynamics of the microbiomes changes within our patients. We’ve seen first-hand how the novel platform and expertise of Microbiome Insights has the potential to rapidly advance not only our understanding of the impact of MRT on patients, but also to uncover valuable microbiome findings for the entire industry.”

“Our scientific team has consulted with leading gastroenterologists to explore ways of leveraging the science on the microbiome and IBD in the clinical setting,” says Microbiome Insights CEO Malcolm Kendall. “Now we have developed the first scientifically robust tool for tracking the microbiome of people with IBD and understanding its link to clinical outcomes. The ability to work with Rebiotix on this path to discovery underscores the future utility of our platform in the clinical setting.”

The companies are continuing to explore applications of Rebiotix interventions and Microbiome Insights’ personal health platform in other microbiome-related diseases.

About Rebiotix
Rebiotix Inc., part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of debilitating diseases using drug products built on its pioneering Microbiota Restoration Therapy™ (MRT) platform. The MRT platform is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com.

About Microbiome Insights
Microbiome Insights, Inc. is a global leader providing end-to-end services for microbiome DNA sequencing, including state-of-the-art bioinformatic analysis. Based in Vancouver, Canada, the company’s customized suite of services enables researchers and clinicians to easily and effectively include microbiome analysis in studies across a range of human, animal, agricultural and environmental applications. The multidisciplinary team of researchers and knowledge leaders at the company provide access to decades of expertise in traditional sciences such as ecology, microbiology, infectious diseases, and genetics. Microbiome Insights’ award-winning team is committed to providing clients with fast, dependable, cost-effective results.

See the original Business Wire press release here.

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