Introduction
In 2022, 50 million people are suffering from sarcopenia, a condition characterized by the loss of muscle mass and strength. Fast forward to 2050, it is projected that the number of individuals diagnosed with sarcopenia will soar to a staggering 500 million. Unfortunately, current solutions for sarcopenia are ineffective and inefficient. Exercise, for instance, hardly works for people with disabilities. Specific drugs designed to treat sarcopenia are conspicuously absent from the medical arsenal. Physical intervention, according to our interview with doctors, has shown only marginal effects in improving sarcopenia. Hence, team PTSH-Taiwan is dedicated to developing a more efficient sarcopenia medication, one that promises improved outcomes for patients and greater accessibility to those in need. This year, we developed Sarcotreat, an engineered live biotherapeutic product that treats multicausal sarcopenia.
Sarcotreat
Sarcotreat is an engineered biotherapeutic product that contains three microorganisms, Kluyveromyces marxianus, Bacillus subtilis, and Clostridium butyricum, as vehicles for drug delivery. It will be consumed by humans and localized in intestines to produce 5 chemicals, butyrate, NMN, astaxanthin, PQQ, and HMB, that can improve sarcopenia. Kluyveromyces marxianus is engineered to produce NMN and Astaxanthin. Bacillus subtilis is engineered to produce HMB PQQ. Clostridium butyricum is not engineered. It can produce abundant butyrate per se.
Gut-muscle axis
The three vehicles were chosen deliberately for their unique and complementary characteristics. Firstly, all three listed microorganisms are part of the normal flora in the gut and are widely used as probiotics in the market, so when they are consumed, they can survive in the human gut and produce the desired beneficial chemicals. Recent studies have shown that healthy intestinal microbiota composition can modulate the immune system, lower oxidative stress, promote muscle synthesis, and enhance mitochondrial biogenesis and function through the gut-muscle axis. Hence, we believe that consuming the three microorganisms, which have the characteristics of probiotics, can help people combat sarcopenia.
The Symbiosis system
Due to their aerobicity, the three microorganisms can complement each other. Bacillus subtilis, generally regarded as an aerobe, can grow under strict anaerobic conditions, such as the human intestines. Kluyveromyces marxianus is a facultative anaerobe, and Clostridium butyricum is an obligate anaerobe. Firstly, the growth of beneficial anaerobic bacteria, so kluyveromyces marxianus will thrive, Bacillus subtilis rapidly consumes oxygen in the intestinal tract, leading to low oxygen conditions in the gut and promoting consumption of more oxygen, providing an ideal habitat for Clostridium butyricum to flourish. Also, Kluyveromyces marxianus can produce prebiotics, a group of nutrients that serve as sustenance for the gut microbiota, further enhancing their growth within the gut. In addition, there is a radial gradient of microbes within the gut, closely linked to the distribution of oxygen and the availability of nutrients provided by the host tissue. Theoretically, the three microorganisms will grow in different parts of the intestine, thereby not competing for the substrates and nutrients with each other, maximizing the efficiency of the system.
Efficacy of the chemicals
Because sarcopenia is a multicausal disease, it's challenging for a single chemical compound to effectively address sarcopenia. Therefore, we deliberately choose five chemicals, butyrate, HMB, astaxanthin, NMN, and PQQ, that address each cause of sarcopenia, including a reduction in muscle protein synthesis, mitochondria dysfunction, cellular oxidative damage, inflammation, and fat accumulation.
| Chemicals | Function |
|---|---|
| Butyrate | Promotion of Muscle synthesis、prevention of muscle cell autophagy、anti-inflammation、prevention of fat accumulation、increase insulin sensitivity、anti-fatigue |
| HMB | Promotion of muscle synthesis、prevention of muscle cell autophagy |
| Astaxanthin | Promotion of muscle synthesis、 prevention of cellular oxidative damage、 promotion of mitochondrial biosynthesis、prevention of fat accumulation、anti-fatigue, prevention of muscle cell autophagy |
| NMN | promote mitochondrial biosynthesis、promote whole-body metabolism, enhance aerobic capacity |
| PQQ | promote mitochondrial biosynthesis、increase mitochondrial efficiency |
Engineering
Through engineering, Sarcotreat has five biosynthesis pathways
Clostridium butyricum cm1
Clostridium butyricum cm1 is not engineered in this project
Bacillus subtilis rm125
Bacillus subtilis rm125 is engineered to produce HMB and PQQ.
Kluyveromyces marxianus km929
Kluyveromyces marxianus km929 is engineered to produce NMN and astaxanthin.
Reference
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