Category Archives: Microbiome Research

Researchers Find Gut Microbes Linked to Depression

Mice experiments and small studies of people with depression have suggested the involvement of the gut microbiome in both behavior and depression, respectively. However, human research addressing how gut microorganisms might contribute to depression—in large samples and considering confounding factors that can affect the microbiota—is lacking.

A new study of two large groups of Europeans, led by Dr. Sara Vieira-Silva and Dr. Jeroen Raes from the Catholic University of Leuven (Belgium), has found new links between gut microbes and depression.

The researchers used 16S ribosomal ribonucleic acid (rRNA) gene sequencing to analyze the fecal microbiota of 1,054 Belgians enrolled in the Flemish Gut Flora Project, aimed at studying gut microbiome variation at population level. Furthermore, microbial taxa were correlated with the participants’ quality of life and incidence of depression, using a self-reported quality of life questionnaire and general practitioner-supplied diagnoses of the latter. The researchers also validated the associations in an independent cohort of 1,063 individuals from the Netherlands’ LifeLines DEEP (LLD) project.

Ten genus abundances were correlated with quality of life scores, including both mental and physical scores. Among these bacterial genera, Faecalibacterium, Coprococcus, Dialister, Butyrivibrio, Gemmiger, Fusicatenibacter and Prevotella were consistently associated with higher quality of life scores, whereas Parabacteroides, Streptococcus and Flavonifractor showed negative associations. After controlling for a wealth of confounding factors, the authors validated some of these associations in the LLD cohort.

The researchers found that Dialister and Coprococcus genera were reduced in people with depression, after taking into account antidepressant drugs as confounders. Furthermore, the authors described an association between enterotype distribution in relation to quality of life scores and diagnosis of depression in the Flemish cohort. For instance, a higher prevalence of Bacteroides enterotype 2 was linked to lower quality of life and depression.

Finally, the authors dug through metagenomic data to create a catalogue describing the gut microbiota’s ability to synthetize or degrade molecules that can cross-talk with the human nervous system. With this aim, Raes and colleagues assessed the distribution of 56 compounds that play an important role in proper nervous system function, which gut microbes either synthesize or metabolize, in human gut-associated microbial genomes (n=532).

Certain neuroactive compounds might explain the beneficial relationship between gut microbes and quality of life. The researchers found, for example, that GABA and tryptophan metabolism pathways were expressed in human gut-associated microorganisms.

Furthermore, some positive correlations were also observed between quality of life and the potential ability of the gut microbiome to produce 3,4-dihydroxyphenyalcetic acid -a breakdown product of the neurotransmitter dopamine-, isovaleric acid and histamine. Of these, the association between 3,4-dihydroxyphenylacetic acid and quality of life was also replicated in the LLD cohort. As neurotransmitters and neuroactive compounds can also have an impact on bacterial growth, further research is needed to disentangle the contribution of microbe-derived neuroactive molecules to a person’s behavior.

This is the first approach to build a database for studying the gut microbiome’s neuroactive potential and it will help future research to interpret microbiome-gut-mental axis research in a clearer way, supporting the translation of such complex research from the bench to the clinic.

Although these new findings do not prove cause and effect due to the observational design of the study, this research contributes to mounting evidence about mechanisms by which the “microbiome-gut-brain axis” is involved in the development of depression. Further options to experimentally prove the association between the gut microbiota and depression might include rodent models and large studies with enough follow-up periods that explore the role of probiotics, prebiotics, a healthy diet and fecal microbiota transplantation for recovering microbiota, considering the confounding effects of microbiome covariates.

On the whole, this new study strengthens the link between gut bacteria and depression. This is a first step towards understanding how the gut microbiome and its metabolites might affect mood in humans

To read the article in its entirety please click on the following link:

https://www.gutmicrobiotaforhealth.com/en/a-large-study-of-belgian-and-dutch-people-finds-new-associations-between-gut-microbes-and-depression/

Rebiotix In Partnership With BioRankings® Develops Microbiome Health Index™ (MHI™) to Identify Indicators for Microbiome Restoration

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat debilitating diseases, announced  on February 12, 2018 — the development of the Microbiome Health Index™ (MHI™) to provide the microbiome research community with a standardized metric to quantify the rehabilitation of the human microbiome.

MHI was established in partnership with data analytics firm, BioRankings®, to enable a non-biased comparison of the efficacy of microbiome-based therapeutics.

New MHI data will be presented at the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2018) in April.

“In developing the Microbiome Health Index, our aim is to provide an objective, universal tool to measure the restoration of a dysbiotic microbiome across different trial designs, sequencing methods and across multiple drug technologies,” stated Ken F. Blount, Ph.D., Chief Scientific Officer of Rebiotix.  “Initial analyses using MHI in Clostridium difficile (C. diff) infections have demonstrated its significant potential to quantify and differentiate dysbiotic from healthier microbiomes.  As presented at ACG2017, MHI was able to quantify the relationship between four key bacterial classes into a single metric that can distinguish patients with dysbiosis resulting from C. diff. From this, we were able to gain valuable insight into the mechanism of action by which Rebiotix’s Phase 3 microbiota drug, RBX2660, is able to rehabilitate a dysbiotic microbiome to a healthier state.”

Blount continued, “MHI is now being employed to analyze microbiome profile data gathered in the ongoing Phase 1 clinical trial of RBX7455, Rebiotix’s lyophilized, non-frozen oral capsule formulation. The intent with this research is to further strengthen and refine MHI and confirm the RBX2660 analysis. Additionally, we will look to utilize MHI in new diseases states being studied.”

Bill Shannon, Ph.D., MBA, Co-Founder and Managing Partner of Analytics at BioRankings said, “The human microbiome is a new frontier where very little analytical methodology or rigorous statistical methods have been developed specifically for this type of data.  Analytical tools such as MHI will be critical to advance translational clinical microbiome research, and we are emboldened by the MHI data that have been reported and continuing to be collected.  Our vision is for MHI to become a standard measure for microbiome research, potentially serving as a validated endpoint for clinical trials and providing both a predictive measure and actionable data.”

MHI provides a unidimensional expression of changes in four taxonomic classes known to have relevance to microbiome health and colonization resistance – Bacteriodia, Clostridia, Gammaproteobacteria and Bacilli.

Utilizing microbiome profiles of patients from the PUNCH CD2 Phase 2b trial of RBX2660, researchers determined that MHI can effectively distinguish patients with dysbiosis from healthier patients, as defined by the RBX2660 product profile and the Human Microbiome Project.  Notably following RBX2660 treatment, MHI significantly increased as early as seven days in responders compared to baseline and continued to increase at day 30 and day 60.

About BioRankings®

BioRankings is a contract analytics firm that works with clients to extract actionable results from their data. Their business philosophy centers on providing clients and partners with the methods, software, and support they need to make full use of their data and design accurate, cost-efficient experiments.  For more information on BioRankings, please visit http://www.biorankings.com.

About Rebiotix Inc.

Rebiotix Inc. is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of challenging diseases. Rebiotix possesses a deep and diverse clinical pipeline, with its lead drug candidate, RBX2660, in Phase 3 clinical development for the prevention of recurrent Clostridium difficile (C. diff) infection.  RBX2660 has been granted Fast Track status, Orphan Drug and Breakthrough Therapy designation from the FDA for its potential to prevent recurrent C. diff. infection. Rebiotix’s clinical pipeline also features RBX7455, a lyophilized, non-frozen, oral capsule formulation, which is currently the subject of an investigator-sponsored Phase 1 trial for the prevention of recurrent C. diff. infection.  In addition, Rebiotix is targeting several other disease states with drug products built on its pioneering Microbiota Restoration Therapy™ (MRT™) platform.  MRT 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 http://www.rebiotix.com.