Targeting Opioid Addiction through the Gut Microbiome
Studying the interaction between the microbiota and substance use disorder to better understand the mechanism that leads to addiction
Opioids are the strongest and the most effective analgesics available for acute pain management. With no viable alternative for treating chronic or post operative pain, it is not surprising that over 10 million people misuse opioids and 75,673 Americans died from opioid overdose in 2021. This is the first known study to explore the developmental influence of the gut microbiota on resistance to addictive behavior and functional connectivity. Northeastern researchers are presently working with the NIH intramural programs on addiction to study the effects of colonizing antibiotic-treated mice with fecal material collected from cocaine, opioid, or nicotine addicted mice that self-administer for drug reward. With the widespread number of opioid receptors found in the gut, studying the interaction between the microbiota and substance use disorder may lead to a better understanding of the mechanism that leads to addiction development as well as potential treatments.
Northeastern researchers are combining noninvasive high field magnetic resonance imaging in awake rodents to evaluate the effect of the gut microbiome on brain structure, function, connectivity and chemistry. Measures from each of these imaging modalities are registered to proprietary 3D MRI atlases (mouse, rat, monkey) with 140-230 segregated, annotated brain areas that allows for cloud based computational analysis and AI interrogation. Germ free (GF) mice which are microbiologically sterile, show a significant reduction in conditioned place preference (CPP) after oxycodone (OXY) opioid exposure when compared to wild type mice (WT). Furthermore, once GF mice are conventionalized i.e., take on the microbiota of WT controls, the CPP reward behavior of these mice mirrors WT mice. The read out in all of the studies is multi model MRI imaging in awake mice and behavioral assays.
Stage of Development
The work is currently at a TRL of 4. Early drug discovery. Identifying those bacteria contributing to risk for drug abuse.
Northeastern researchers combine multimodal MRI with behavior to understand changes in brain function and connectomics that are influenced by the gut microbiome. The use of noninvasive MRI allows for longitudinal studies of drug resistance and drug sensitivity in the same animals. The data collected from imaging is easily translated to the human condition and can be replicated on human scanners, a key feature in Phase 1 clinical trials looking for a CNS readout of gut to brain interaction.
CNS therapeutics designed to affect behavior by targeting specific GPCRs have not realized their potential. This approach of manipulating the gut with different types of bacteria, antibiotics, drugs or conditions that favor a certain microbiome may be a more effective approach to affecting behavior than traditional neuropharmacology. The approach taken in these studies combining MRI with behavior for drug abuse can also be applied to depression, psychosis, anxiety disorders, stroke, and head injury.
Support the science on the identification and ultimately the genetic manipulation of bacteria or drugs that specifically alter the genotype and behavioral phenotype of the gut microbiome.
- Patent application submitted
- Development partner