Understanding the mechanism of action (MOA) of probiotic strains is a cornerstone of modern microbiome research and product development. While traditional in vitro assays offer preliminary insights, they often fall short in replicating the intricate host-microbe interactions that govern real-world outcomes. Disease-relevant cell and animal models have thus emerged as indispensable tools for uncovering the molecular, cellular, and systemic pathways influenced by live biotherapeutic products (LBPs).

At Creative Biolabs, we offer comprehensive MOA screening services using physiologically relevant in vitro and in vivo models tailored to various disease states. Our advanced platforms support a range of probiotic candidates, from next-generation strains to genetically engineered microbes, delivering the scientific confidence needed to move forward in development pipelines.

Fig. 1 Probiotic MOA Screening Across Multi-Model Systems. (Creative Biolabs Original)

Why MOA Screening in Disease Models is Crucial for Probiotic R&D

Bridging the Translational Gap

Most probiotic effects are highly context-dependent, modulated by the host immune system, gut epithelium, metabolic state, and even neural signaling pathways. Understanding these complex interactions requires more than conventional assays. Disease-relevant models provide the translational bridge between bench and in vivo biology, mimicking real-world physiological and pathological conditions.

High Market Demand and Regulatory Expectations

With the rise of next-generation probiotics and increased regulatory scrutiny around health claims, there is a growing demand for detailed MOA data. Both investors and regulatory agencies now expect clear, reproducible evidence of function. Disease-relevant models allow companies to meet these expectations by generating meaningful, mechanism-based data to support product development and regulatory submissions.

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Creative Biolabs' MOA Screening Capabilities

Creative Biolabs offers a robust suite of disease-relevant model systems to interrogate the biological effects of probiotic strains across multiple organ systems. All models are customizable and executed under rigorous quality-controlled workflows.

In Vitro Cell-Based Disease Models

  • Inflammation Models: Use of Caco-2, HT-29, and THP-1 derived systems to study cytokine regulation, barrier integrity, and NF-κB pathway modulation.
  • Gut-Brain Axis Models: Co-culture of intestinal epithelial cells and neuronal cell lines (e.g., SH-SY5Y) to explore neuroactive compound production.
  • Metabolic Models: Adipocyte and hepatocyte systems to investigate SCFA-induced modulation of glucose and lipid metabolism.
  • Epithelial Barrier Dysfunction: TEER measurement in monolayered intestinal cells to assess barrier reinforcement or disruption.

Ex Vivo Organoid and Co-Culture Platforms

  • Intestinal Organoids: Patient-derived or murine organoids to assess epithelial cell response to probiotic metabolites or surface molecules.
  • Immune Co-Culture: Integration of dendritic cells, macrophages, or PBMCs with gut models for immune activation profiling.
  • Macrophage-Organoid Co-Culture: Enables the study of epithelial-immune interactions in the presence of probiotics under inflammatory conditions.

In Vivo Disease Models

  • IBD Models (e.g., DSS, TNBS-induced colitis): Monitor disease activity index, histopathology, cytokine profiles, and gut microbiota shifts.
  • Metabolic Syndrome Models: High-fat diet-fed mice to assess weight gain, insulin resistance, and serum lipid regulation.
  • Neuroinflammation Models: Probiotic impact on microglial activation and behavior in models of Parkinson's or Alzheimer's disease.
  • Allergic Asthma Models: Airway hyperresponsiveness, eosinophil infiltration, and cytokine levels as endpoints.
  • Germ-Free and Gnotobiotic Models: Controlled colonization experiments for strain-specific MOA elucidation.

Our End-to-End Service Workflow

To ensure clarity and reliability, each MOA screening project follows a stepwise approach customized to client needs:

Fig. 2 Probiotic MOA Screening in Disease Models Workflow. (Creative Biolabs Original)

What You Will Receive: Detailed and Actionable Deliverables

Clients engaging Creative Biolabs for MOA screening in disease-relevant models will receive a comprehensive suite of deliverables designed to support downstream applications:

  • Full experimental protocol and SOP documentation
  • High-resolution raw data (images, flow cytometry plots, ELISA outputs, etc.)
  • Statistical analysis of key outcomes
  • Graphical summary of the proposed MOA
  • Heatmaps or volcano plots (for transcriptomics/metabolomics endpoints)
  • Annotated interpretation of results with suggested next steps
  • Optional publication-ready figures and text draft support

Applications of Disease-Relevant MOA Screening

Preclinical Candidate Validation

Screening in pathophysiologically relevant systems helps identify the most promising strains early in the development cycle. This minimizes downstream attrition and streamlines decision-making on clinical progression.

Regulatory Submission Packages

Disease-relevant MOA data supports health claim substantiation, IND filing, and classification of probiotics as either foods, dietary supplements, or live biotherapeutic products (LBPs), depending on jurisdiction.

Intellectual Property and Patent Filing

Mechanism-level differentiation can serve as a unique selling point and strengthen IP portfolios through claimable biological functions linked to specific strains or consortia.

Mechanistic Comparisons of Strain Variants

Disease-relevant models allow side-by-side comparisons of engineered strains versus wild-type to highlight enhanced functionalities or safety profiles.

Functional Microbiome Research

By mapping molecular interactions between probiotics and host systems, researchers can better contextualize metagenomic findings and link taxa to function.

Explore Other Services from Creative Biolabs

To support comprehensive probiotic development, Creative Biolabs provides a wide array of integrated services:

Whether you're at the early stages of screening or refining a preclinical candidate for regulatory readiness, Creative Biolabs offers the tools and expertise to generate reliable, high-resolution MOA data in disease-relevant systems. Our dedicated scientific team will work closely with you to design studies that match your unique objectives and budget.

Let's build functional insight into your strain development pipeline.

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FAQs

What types of disease models are available for probiotic MOA screening at Creative Biolabs?

We offer a wide range of in vitro, ex vivo, and in vivo models, including colitis, metabolic syndrome, neuroinflammation, epithelial barrier dysfunction, and gut-brain axis systems, all customizable to match your specific probiotic research goals.

What endpoints are typically measured during MOA screening?

We assess a wide array of endpoints, including cytokine profiles, epithelial integrity, microbial shifts, signaling pathway activation, metabolic biomarkers, and host behavior—depending on the chosen model and study scope.

How customizable is the service workflow for unique research needs?

Highly customizable. We tailor each project's design, dosing, endpoint selection, and data analysis in close collaboration with you to ensure alignment with scientific objectives and regulatory or development milestones.

Other Resources

References

  1. Anjum, Mehreen, et al. "Current perspectives on gastrointestinal models to assess probiotic-pathogen interactions." Frontiers in Microbiology 13 (2022): 831455. https://doi.org/10.3389/fmicb.2022.831455
  2. Lopez, Alejandra Rojas, and Matteo Barberis. "Metabolic modeling for probiotic and prebiotic production to treat inflammatory disorders." Chemical Engineering Journal 502 (2024): 157852. https://doi.org/10.1016/j.cej.2024.157852
  3. Yan, Fang, and D. Brent Polk. "Probiotics and probiotic-derived functional factors—Mechanistic insights into applications for intestinal homeostasis." Frontiers in immunology 11 (2020): 1428. https://doi.org/10.3389/fimmu.2020.01428
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