Team:SZU-China/Relative Abundance Analysis


Relative Abundance Analysis


Focusing on patients suffering from IBD, we expect to provide them with treatments through cocktail therapy. Planting different proportions of engineered bacteria into the human colon to regulate the flora in the human intestine is what we are working on. However, there are many problems involved. The flora in the human body is not eternal but in the process of dynamic change. We have ensured the safety of engineered bacteria from various aspects of resistance and suicide switch.

While making breakthroughs in experiments, we carried out a series of modeling work, then the entire treatment progress is carried out in this closed-loop. In the process of patient follow-up treatment, using stool detection technology, we can monitor and analyze the changes in the biological flora of the patient in real-time. After that, we can produce engineering bacteria drugs according to this ratio, and provide the patient with the most suitable bacterial adjuvant for his own situation. We will also customize a diet plan for the patient and ask him to record his daily diet so that we can predict changes in his intestinal flora in advance.

Until the next patient’s stool sample is received, analysis and testing will be performed again. With this model, we believe we will promote the application and development of genetic engineering treatments in precision medicine greatly.

1. Above all, we want to declare that the data in this model is not real human data. Instead, we searched for a large number of cases from the fecal bacteria transplantation database.

2. Specifically, we plan to provide patients and hospitals with our self-developed stool collection device so that they can collect samples. We will collect the patient’s stool samples, perform whole-genome sequencing, analyze the composition of the patient’s intestinal flora, and use qPCR technology to analyze the dynamic changes of the patient’s intestinal flora, and finally use the relative abundance analysis method to present the patient’s intestinal bacteria’s changes within a certain period of time.

3. In the detection of fecal bacteria, the types and data of a large number of bacteria can be obtained very finely. In order to make the model simpler, we only show the relative abundance analysis of ten selected bacteria that are highly similar to our engineered bacteria. Nevertheless, when it is applied to patients in the future, this model should have a more detailed and optimized version.

Highly Approximated Bacteria

We hope to design engineered bacteria to express SOD, LL-37, BSH, and butyric acid in the human body to change the environment of human intestinal flora. Among them, butyric acid is highly expressed in the human body. Before the colonization of engineered bacteria into the human body, we selected several high-expressing SOD, BSH, LL-37 bacteria from the human intestinal beneficial flora to make a high degree of approximation.

Fig.1 Species stacking figure.

Streptococcus thermophilus

Streptococcus Thermophilus is a powerful probiotic strain that has well researched health benefits. This probiotic is often found in the colon and has many digestive, immunity & many other researched health benefits. They improve the intestinal microenvironment: promote intestinal peristalsis to prevent harmful bacteria from planting, secreting bacteriocin to inhibit the growth of harmful bacteria. They also produce superoxide dismutase (SOD) that removes excess superoxyoxy anion free radicals produced during metabolism in the body.

Fig.2 Changes of Streptococcus thermophilus

Clostridium butyricum

Clostridium butyricum is one of the normal intestinal bacteria in people, strictly anaerobic, for Gram-positive bacteria. The resulting tyroic acid is also called butyric acid. Clostridium butyricum into the intestines, in their own rapid reproduction at the same time, the breakdown of food polysaccharides for oligosaccharides, promote the rapid growth of other beneficial bacteria in the intestines, it can also inhibit the growth of intestinal harmful bacteria such as dysentery Shigella, restore the balance of intestinal flora, reduce the production of amines, ammonia, pyridoxine and other intestinal toxins and poisoning of the intestinal mucosa, restore intestinal immune function and normal physiological function. It has the ability to contract short-chain fatty acids and is antibacterial to Clostridium difficile and Helicobacter pylori function.

Fig.3 Changes of Clostridium butyricum

Bifidobacterium longum

Bifidobacterium longum, considered to be the earliest inhabitant of the baby's intestines, has a high proportion of infant gut microorganisms. Although it is relatively low in the adult gut, the lactic acid it produces is thought to inhibit the growth of pathogenic microorganisms. Bifidobacterium longum have strong adhesion to intestinal endotheat cells, can be permanently planted in the intestines, while some strains of bifidobacterium longum have been found to be highly resistant to stomach acid bile, can survive in the gastrointestinal tract and in the small intestine and large intestine. Bifidobacterium longum is cons idered a scavenger and has a variety of decomposing metabolic pathways to use a variety of nutrients to increase its competitiveness in the gut flora. Bifidobacterium longum also has several glyco-based hydrolyzed enzymes metabolizing complex oligosaccharides to obtain carbon and energy.

Fig.4 Changes of Bifidobacterium longum.

Eubacterium hallii

Eubacterium hallii is an anaerobic, Gram-positive, catalase-negative bacterium belonging to the Lachnospiraceae family of the phylum Firmicutes that is present in both murine and human faeces. 8 E. hallii is a butyrate-producing species.

Eubacterium hallii
Fig.5 Changes of Eubacterium hallii.

Clostridium leptum

Clostridium leptum is a main member of phylum firmicutes. It is one of the most abundant bacteria in the intestines of healthy people, and has a high host specificity, which can reflect the situation of host digestive system. It can reflect the situation of the host digestive system, regulate the micro-ecological balance of the intestine, speed up the formation of blood vessels in the intestinal mucosa, promote the development of the immune system, inhibit the invasion of pathogenic bacteria. It produces butyric acid and vitamins, butyrate plays an important role in the host's energy supply and the development of intestinal epithelial cells. To some extent, it inhibits the occurrence of colon cancer. Its absence can cause bowel disorders, and the bacteria is less abundant in patients with Crohn's disease.

Clostridium leptum
Fig.6 Changes of Clostridium leptum.

Roseburia intestinalis

Roseburia intestinalis is a saccharolytic, butyrate-producing bacterium first isolated from human faeces.It is anaerobic, gram-positive, non-sporeforming, slightly curved rod-shaped and motile by means of multiple subterminal flagella. It can help improve flora composition and has the potential to treat Crohn's disease.

Roseburia intestinalis
Fig.7 Changes of Roseburia intestinalis.

Ruminococcus bromii

The Ruminococcus bacteria in human's gut microbiomes play a major role in helping us digest resistant starches – the complex carbohydrates found in high fiber foods such as lentils, beans, and unprocessed whole grains. Then they promotes the production of short-chain fatty acids, especially the growth of butyric acid-producing bacteria.

Ruminococcus bromii
Fig.8 Changes of Ruminococcus bromii.

Bifidobacterium pseudocatenulatum

Bifidobacterium pseudocatenulatum, are among the dominant microbial populations of the human gastrointestinal tract. They are also major components of many commercial probiotic products. They can improve metabolic and immunological changes associated with obese mice.

Bifidobacterium pseudocatenulatum
Fig.9 Changes of Bifidobacterium pseudocatenulatum.

Bifidobacterium bifidum

Bifidobacterium bifidum can treat chronic diarrhea. Harmful bacteria in the human intestine produce and release toxins into the bloodstream, which can cause serious damage to the liver, bifidobacterium bifidum can inhibit the number of harmful bacteria that produce toxins, thus playing a good therapeutic role in liver patients. Bifidobacterium bifidum can affect the metabolism of cholesterol, converting it into steroids that the body does not absorb, and lowering the concentration of cholesterol in the blood.

Bifidobacterium bifidum
Fig.10 Changes of Bifidobacterium bifidum.

Lactobacillus acidophilus

Lactobacilli acidophilus are bacteria. They are also called L. acidophilus. They make lactic acid by breaking down carbohydrates. This is mainly done by breaking down the sugar lactose in milk. They can also be found in the intestinal tracts and vaginas of adults and in the intestinal tracts of babies fed with formula. L. acidophilus has been used to control certain types of diarrhea. It may be helpful for diarrhea due to oral antibiotics. These medicines kill the normal flora of the intestine. Consuming L. acidophilus helps put good bacteria into the intestines. This often stops diarrhea. It may also help treat vaginal yeast infections.

Lactobacillus acidophilus
Fig.11 Changes of Lactobacillus acidophilus.
Before and After Treatment

Use an algorithm to express the relative abundance of the flora changes in patients before and after a specific treatment. According to the test data, it is obvious that the corresponding flora has increased after treatment.

Fig.12 Relative Abundance Analysis :fitting result.
Update Personalized Treatment

Next, we will also refer to this model to provide personalized and customized adjuvants for patients. For example, there is no obvious change in this bacteria. It can be considered that there is still a lack of BSH-producing bacteria in the intestine. Our mini-program shall increase the proportion of BSH-producing engineered bacteria to improve patients’ intestinal flora in our related follow-up treatment.

The relative abundance model complements the entire closed-loop of our project. Looking forward to providing more refined analysis and treatment plans and making a certain contribution to the treatment of IBD patients.

Next, we will also refer to this model to provide personalized and customized adjuvants for patients. For example, there is no obvious change in this bacteria. It can be considered that there is still a lack of BSH-producing bacteria in the intestine. Our mini-program shall increase the proportion of BSH-producing engineered bacteria to improve patients’ intestinal flora in our related follow-up treatment.


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