For individuals living with chronic conditions such as rheumatoid arthritis, treatment often involves lifelong injections. However, the challenges associated with needle-based therapies—including fear of needles, the risk of injection-associated infections, and pain—frequently result in patients skipping doses. This non-compliance drives the need for innovative delivery strategies that combine efficacy with convenience and limited side effects.
Researchers at Baylor College of Medicine and collaborating institutions have pioneered a groundbreaking alternative: an oral drug delivery system that could eliminate the need for injections. This transformative study, published in the Proceedings of the National Academy of Sciences, explores the use of probiotic bacteria as a novel drug delivery platform.
A Probiotic Solution: L. reuteri as a Drug Delivery Platform
“People don’t like to have injections for the rest of their lives,” says Dr. Christine Beeton, professor of integrative physiology at Baylor and co-corresponding author of the study. Her team investigated using the probiotic bacteria Lactobacillus reuteri as a delivery vehicle for medications in a rat model of rheumatoid arthritis.
This novel approach builds on previous research by Beeton’s lab, which demonstrated that a peptide derived from sea anemone toxin could effectively reduce disease severity in both animal models and patients with plaque psoriasis. However, while effective, this peptide therapy requires repeated injections and oral delivery has historically shown low efficacy.
To overcome these limitations, Beeton collaborated with Dr. Robert A. Britton, professor of molecular virology and microbiology at Baylor. The Britton lab has developed expertise in genetically modifying probiotic bacteria to produce and release therapeutic compounds. By bioengineering L. reuteri, the team created a strain capable of secreting the therapeutic peptide ShK-235 derived from sea anemone toxin.
Why Lactobacillus reuteri?
Several factors make L. reuteri an ideal choice for this innovative platform:
Gut Compatibility: As an indigenous bacteria found in human and animal guts, L. reuteri is well-suited for long-term use in therapeutic applications.
Safety Profile: This lactic acid bacterium has a well-established safety record, recognized by the U.S. Food and Drug Administration as safe for infants, children, adults, and even immunocompromised individuals.
Ease of Use: Unlike injectable therapies, this probiotic can be administered orally, potentially stored in capsules without refrigeration.
Transient Colonization: L. reuteri does not remain in the gut permanently, as it is removed during the regular renewal of the gut’s inner surface. This feature allows for precise regulation of treatment administration.
Encouraging Results in Animal Models
The bioengineered strain, dubbed LrS235, was tested in animal models of rheumatoid arthritis. Daily administration of LrS235 significantly reduced clinical signs of the disease, including:
- Joint inflammation
- Cartilage destruction
- Bone damage
The team tracked the peptide ShK-235 produced by LrS235, confirming its presence in the bloodstream after oral administration. These findings demonstrate the potential of probiotic-based delivery systems to achieve systemic therapeutic effects.
Implications for Patient Convenience
One of the major benefits of this approach is its simplicity. “These bacteria could be stored in capsules that can be kept on the kitchen counter,” says Beeton. Patients could take their medication orally without the need for refrigeration, needles, or frequent doctor visits, making treatment more accessible and less burdensome.
Broader Applications in Chronic Disease Management
The success of LrS235 as a drug delivery platform opens doors for broader applications. Probiotic-based delivery systems could potentially be used for:
- Peptide-based therapies in other chronic inflammatory diseases
- Drugs that currently require injections or have poor oral bioavailability
- Personalized medicine, where probiotics are tailored to individual patients’ needs
Next Steps: Clinical Development
While the study’s results are promising, further research is needed to transition this innovation into clinical practice. Key areas of focus include:
- Safety Studies: Evaluating long-term effects in diverse populations
- Efficacy Trials: Conducting human clinical trials to confirm therapeutic benefits
- Regulatory Approvals: Ensuring compliance with FDA and other global health regulations
Funding and Collaboration
This project highlights the collaborative efforts of researchers and the importance of funding for innovative science. Support for this study was provided by the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine, Bridge Funding from Baylor, and grants from the Cancer Prevention and Research Institute of Texas, the National Institutes of Health, and the Dan L Duncan Comprehensive Cancer Center.
Conclusion
The development of an oral probiotic-based drug delivery system represents a paradigm shift in treating chronic conditions. By leveraging bioengineered bacteria, researchers have paved the way for more patient-friendly and effective therapies. With further research, this innovative approach could revolutionize chronic disease management, offering hope to millions of patients worldwide.
Contributors: Yuqing Wang, Duolong Zhu, Laura C. Ortiz-Velez, Jacob L. Perry, Michael W. Pennington, and Joseph M. Hyser.
Funding Sources: Alkek Center for Metagenomics and Microbiome Research, Cancer Prevention and Research Institute of Texas, and the National Institutes of Health.
This article was inspired by research conducted at Baylor College of Medicine
