AOBiome - Human Microbiome
From Science
The human microbiome consists of hundreds of trillions of microorganisms, outnumbering human cells by 10 to 1 with as many as 3 million bacterial genes to our approximately 20 thousand. While the microbiome has recently become an area of active research, its overall effects on human health remain largely unknown.
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Bacteria from the human microbiome were among the first ones ever described by Antony van Leeuwenhoek, the “Father of Microbiology”. Despite that, until recently the studies of human-associated bacteria have been almost exclusively focused on pathogens. This has led to many advances in medicine and public health, including sterilization, antimicrobials, and antibiotics, however a vast number of other beneficial microorganisms that could critically impact human health have historically gone largely unstudied.
While pathogenic bacteria can be present in our microbiome, it also contains a vast number of commensal organisms that are either non-pathogenic or can only become pathogenic under very specific conditions. In addition to not being pathogenic, these commensal bacteria are increasingly shown to have beneficial functions such vitamin K processing and the breakdown of complex carbohydrates, increasing their bioavailability.
If these natural commensal bacteria are eliminated by antibiotics or other means, an imbalance in the microbiome occurs. Clostridium difficile (C. diff), for example, causes life-threatening gut infections in people who have been taking antibiotics, killing 14,000 people per year in the US. When commensal bacteria are reintroduced by a simple transplant of gut flora from a healthy individual, the Clostridium infection is often resolved. This illustrates that maintaining a balanced microbiome safeguards human health.
AOBiome’s work focuses on re-introducing beneficial commensal bacteria such as Ammonia Oxidizing Bacteria to the human microbiome.
The Nitrogen Cycle in Humans
Similar to the carbon or oxygen cycle, the nitrogen cycle is critical to life. One of the key components of the nitrogen cycle is Nitric Oxide (NO) which is small and rapidly permeates cell membranes and aqueous solutions. As it is also highly reactive, it gets depleted easily within the body and its range is relatively short. Because of its potential to interact with almost every protein, we are only beginning to understand the many effects of the NO/NOx signaling in cells and the human body. For example, in the brain, NO modifies ion channels, such as glutamate receptors, and reversibly changes their properties.
NO signaling has been comparatively well studied in the regulation of blood flow, which earned its discoverers a Nobel Prize in 1998. Nitroglycerin, which has been used to treat chest pain due to heart ischemia since 1878, works by being converted to nitric oxide, dilating the blood vessels, decreasing heart workload, and improving heart oxygenation. Erectile disfunction drugs such as Viagra and Cialis exert their effect through the same pathway. They block cGMP degradation, extending the action of locally produced NO and thus increasing inflow of blood into the tissue in question.
Finally, the NO/NOx signaling system is very important in regulating inflammation. Low concentrations of NO down-regulate inflammation by inhibiting cell adhesion, cytokine and chemokine production and leukocyte adhesion and migration. NO-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) are new therapeutic agents.
The Ammonia Oxidizing Bacteria studied by AOBiome consume ammonia as their food source and produce NO.
AOB, Inflammatory Conditions, and Systemic Effects
AOB, Inflammatory Conditions, and Systemic Effects
We have identified significant therapeutic opportunities caused by the adverse impact of the modern environment on human physiology. The human body relies on a system of multiple microorganisms, chemistries, and pathways which have evolved with humans for millennia, and that together are essential to human health. When these microorganisms are imbalanced, or dysbiotic, the human body can be more susceptible to disease. Due to the widespread use of surfactants, antimicrobials, antibiotics, and general “sterilization,” these vital microorganisms have been stripped out of the modern human body and the living environment. In parallel, the incidence rates of systemic and inflammatory diseases have risen over the course of modern history. However, populations that live closer to natural environments, without the use of chemicals and the focus on antimicrobials, have been shown to be healthier in many respects. For example, a recently published peer-reviewed article examined three populations of similar genetic background, an Amish cohort that lives both close to nature on farms in the rural United States and refrains from the use of modern technology such as modern hygiene products and technology, a Swiss population that lives close to nature on farms but otherwise utilizes modern hygiene products and technology, and a non-farm, Swiss cohort practicing a modern lifestyle. The authors observed that only 7.2% of children in the Amish group had been diagnosed with atopy, a predisposition toward developing certain allergic hypersensitivity reactions, as compared to 25.2% of children in the Swiss farm group and 44.2% of the non-farm Swiss children. We believe that restoration of the symbiotic relationship between bacteria and human beings will have a profound effect on human health.
AOB, whose sole source of energy is ammonia, play a critical role in the nitrogen cycle. In the presence of oxygen, AOB consume ammonia and produces nitric oxide, or NO, and nitrite (see Figure 1 below). NO is a key signaling molecule integral to the circulatory system, the central nervous system and systemic response in the human body and is involved across numberous biological systems. NO was proclaimed the “Molecule of the Year” by the journal Science and the 1998 Nobel Prize in Physiology or Medicine was awarded for discovering NO’s role as a cardiovascular signaling molecule and is a well-documented vasodilator with anti-inflammatory properties. AOB also modulates nitrite.
The metabolism of ammonia by AOB lowers local pH levels, and due to its unique metabolic activity, AOB has both first order and second order effects on the human body, including (i) rearrangement of the microbiome, including an observed local reduction in known pathogenic bacteria, (ii) reduction in local pH, and (iii) production of known anti-inflammatory and vasodilatory compounds. Although microbiomes are often difficult to characterize given the transient nature of bacteria, we have shown that the presence of AOB is correlated with a reduction in populations of bacteria that are commonly associated with disease including Staph.aureus and P.acnes, which are associated with eczema and acne, respectively. AOB’s anti-inflammatory and pH-lowering properties, and its ability to reduce levels of pathogenic bacteria, coupled with our earlier anecdotal feedback from the Cosmetic Product, led us to undertake our clinical trials described below.
The following figure shows the conversion by B244, our proprietary strain of AOB, of ammonia into nitrite and nitric oxide:
We are using the same active ingredient, B244, a l...
We are using the same active ingredient, B244, a live single strain of Nitrosomonas eutropha, in different potencies and formulations tailored to each of our clinical trials, and we initially targeted inflammatory conditions that are not well served by current therapies either due to lack of efficacy or intolerable side effects. We currently have six programs conducting clinical trials: AOB101 for the treatment of acne; AOB102 for the treatment of atopic dermatitis, or eczema, and associated pruritus; AOB103 for the treatment of rosacea, AOB201 for allergic rhinitis; AOB202 for migraines and AOB203 for hypertension. In all of our clinical studies, we have observed a very favorable tolerability profile, with no signs of hypersensitivity reactions, inflammatory reactions, localized infections, bacteremia or sepsis or any serious adverse events.
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