Live biotherapeutic products (LBPs) are a class of therapeutic agents containing live microorganisms that confer health benefits when administered in adequate amounts. They have garnered significant attention for their potential to treat various conditions, including gastrointestinal disorders, metabolic diseases, and even mental health issues.

These microorganisms, often bacteria, are carefully selected strains known to positively influence the host's microbiota—the diverse community of microorganisms inhabiting the human body—and overall well-being. Disruptions in the microbiota, known as dysbiosis, have been linked to numerous diseases, highlighting the significance of interventions such as LBPs in restoring microbial balance. Seizing the therapeutic benefits of commensal bacteria, microorganisms that inhabit various parts of the human body without causing harm, could offer a promising route for disease control and prevention via LBPs.

In addition to naturally occurring microorganisms, genetically engineered bacteria can be used for targeted drug delivery. Engineered bacteria can be designed to produce and release therapeutic compounds at specific sites within the body, enhancing treatment efficacy while minimizing side effects. This approach offers precision and control in drug delivery.

Five companies leading the way in applying microbiota science to address medical challenges include NeribiOm, EverImmune, Azitra, Siolta Therapeutics, and P. Happi. These challenges include neurological disorders, cancer treatment, skin diseases, maternal-infant health, and women's intimate well-being.

NeribiOm: Improving Brain Health through the Microbiota-Gut-Brain Axis

NeribiOm, founded in 2017, advances treatments for neurological and psychiatric disorders. It specializes in the bioengineering of probiotic bacterial strains alongside their prebiotics—food ingredients that help beneficial bacteria grow in the gut and are important for mental health.

There is a growing body of evidence suggesting that the microbiota-gut-brain axis—the bidirectional communication network between the gut (and its microbiota) and the central nervous system—plays a significant role in neurological and psychiatric conditions. Recent findings indicate that imbalanced gut microbial colonization is associated with various brain disorders, including Parkinson’s disease, Alzheimer’s disease, and autism spectrum disorders. NeribiOm’s research focuses on restoring equilibrium within this axis, aiming to develop targeted interventions that modulate gut microbiota to positively influence central nervous system function.

NeribiOm is exploring the potential of psychobiotics, a subset of probiotics with specific mental health benefits for patients with psychiatric illnesses. These psychobiotics exert their effects by modulating neurotransmitter levels, neuroinflammation (inflammation occurring in the brain or central nervous system), and neural signaling pathways. These effects offer promising avenues for managing psychiatric disorders.

Furthermore, NeribiOm is pioneering the development of neurosynbiotics—custom-designed probiotics tailored to address the complexities of neurological disorders. These neurosynbiotics have the potential to mitigate symptoms and slow disease progression in conditions such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis.

EverImmune: Fighting Cancer with Bacteria

EverImmune is a biotechnology company focusing on microbiota oncology, a specialized field within cancer research that explores the relationship between human microbiota and the development, progression, and treatment of cancer. Founded in 2016 by Professor Laurence Zitvogel and Dr. Romain Daillere, EverImmune is a spinoff from the cancer-research hospital Gustave Roussy.

EverImmune develops LBPs designed to exploit the dynamics of the gut microbiota, thereby enhancing the efficacy of cancer immunotherapies. The company centers its approach around identifying and cultivating key bacterial commensals, particularly Akkermansia, which play a pivotal role in shaping the effectiveness of anticancer treatments. Through preclinical validation, EverImmune identified Oncobax AK as a well-defined, freeze-dried, and encapsulated strain of Akkermansia. This strain is primed to enhance the efficacy of cancer immunotherapy using immune checkpoint inhibitors such as PD1—a treatment that helps the immune system fight cancer cells.

Preclinical studies have demonstrated Oncobax AK’s ability to restore immunotherapy efficacy in mice models resistant to anti-PD1 treatment. This marks a promising step toward its use in human treatments. Phase 1 clinical trials, which assess safety and dosage, began in 2023.

In addition to developing therapeutic products, EverImmune is cultivating microbiota-based diagnostic tools. These tools aim to predict and personalize therapeutic interventions for cancer treatment.

Azitra: Dermatological Treatment through Genetic Engineering of Bacteria

Azitra, a clinical-stage biopharmaceutical company, specializes in the genetic engineering of bacteria for medicinal purposes. Its primary objective is to address skin diseases through treatments combining engineered proteins and LBPs.

Azitra’s core methodology revolves around a specialized platform featuring microbial collections comprising approximately 1,500 unique bacterial strains. This extensive collection serves as the foundation for screening and identifying strains with distinctive therapeutic attributes. Augmented by artificial intelligence and machine learning, this platform enables Azitra to analyze and predict the therapeutic potential of microbial strains.

The company focuses on the development of genetically engineered strains of Staphylococcus epidermidis (S. epidermidis), a species renowned for its beneficial properties in dermatological applications. One key initiative involves utilizing engineered microbes for microbial drug delivery. This method aims to overcome challenges associated with conventional topical protein delivery, such as limited skin penetration and enzymatic degradation. By engineering bacteria to release therapeutic proteins directly into the skin, Azitra seeks to enhance treatment efficacy and improve patient outcomes.

One of Azitra’s drug candidates, ATR-12, is already in Phase 1 human clinical trials. ATR-12 targets Netherton syndrome, a chronic pediatric rare disease affecting the skin caused by a genetic mutation that results in the absence of an enzyme important for regulating skin shedding. ATR-12 is a bacterial strain engineered to deliver the missing enzyme directly into the skin.

Siolta Therapeutics: Targeting Diseases in the Maternal-Infant Axis

Siolta Therapeutics is a biotechnology company with a strong focus on the maternal-infant axis—the interplay between a mother and her infant that influences various physiological and developmental processes.

The gut microbiome plays a critical role in immune maturation and early-life development. Dysbiosis during this stage can lead to diseases with long-lasting effects, including eczema, food allergies, and allergic asthma. These conditions pose significant global health challenges, particularly among children, and there are limited options for prevention and treatment.

Siolta Therapeutics recognizes the importance of proper gut microbiota development. At the core of its work lies the Precision Symbiotics Platform, which enables the design of microbial combinations aimed at modulating microbiome development. The company actively develops LBPs to address diseases within the maternal-infant axis. One of their most advanced products is STMC-103H, which targets the prevention of atopic diseases (a subset of allergic diseases) in newborns. Siolta aims to intervene early in at-risk individuals to prevent the onset of these diseases, thereby reducing chronic morbidity and healthcare burdens. Additionally, the company plans to explore STMC-103H's effectiveness in treating atopic diseases. The product is currently in Phase 2 human clinical trials, which evaluate treatment efficacy and monitor potential side effects.

P. Happi: Bacterial Solutions for Women’s Health

The female genital tract is naturally colonized by mixed communities of bacteria, forming the vaginal microbiome. These communities consist of trillions of microorganisms, primarily bacteria, along with some fungi and viruses. The balance of the vaginal microbiome is crucial for maintaining genital health. Disruptions can have significant consequences. A healthy microbiome is associated with optimal fertility, while imbalances may affect conception and reproductive outcomes.

P. Happi, founded in 2019 in London, advances women’s intimate health through microbiome science. Its first product, a microbiome-protective intimate serum, features the bacterium Bdellovibrio bacteriovorous (B.Y.M. 1405).

When applied to the intimate area, the serum activates B.Y.M. 1405, establishing a robust defense against harmful bacteria by forming a protective bio-barrier. This barrier mitigates the risk of intrusion by undesirable bacteria, including those originating from the bowel.

The company's unique approach involves applying the serum directly to the vulva and perineum to form a physical barrier, rather than relying on oral supplements. By targeting the intimate area externally, the serum ensures effective delivery of B.Y.M. 1405 without needing to navigate metabolic barriers or circulate throughout the body.

The Potential of Live Biotherapeutic Products in Modern Healthcare

The rise of live biotherapeutic products (LBPs) is reshaping healthcare by using live microorganisms to restore and maintain a balanced microbiota or used for targeted drug delivery. Companies like NeribiOm, EverImmune, Azitra, Siolta Therapeutics, and P. Happi are leading the way in developing treatments for various conditions. Their efforts highlight the significant potential of microbiome-based therapies to provide targeted and effective treatments.Looking forward, the field of LBPs holds considerable promise. Ongoing research and clinical trials will be essential in overcoming challenges such as regulatory issues and ensuring long-term effectiveness. As scientific understanding advances, LBPs may become integral to personalized medicine, offering new solutions for managing and treating a range of health conditions.