Vy Vo – Microbial Influences on Human Health 323

If I was the head of a funding agency (like the National Institute of Health) in which my job is to look at proposals for research projects and decide what projects to award funding to, the research that I would be most excited about fundings as it related to learning more about microbial influences on human health is Helicobacter Pylori (H.pylori) effects. As I learned from the first few weeks of this term about H.pylori and its effects on human health due to diseases such as gastritis, atherosclerotic disease, and development of gastric cancer as well. It led me to H.pylori eradication to protect human from these diseases above. However, when I worked on my final paper, I found the controversial information about H.pylori in  Gastroesophageal reflux disease (GERD), Inflammatory bowel diseases (IBD), allergy, and asthma. Also, in the article “What are the consequences of the disappearing human microbiota?”, the authors talked about the disappearance of H.pylori  which is salutary for human in order to prevent gastric cancer, but the oesophageal reflux, Barrett’s esophagus and adenocarcinoma increase. I raised a question whether people should have H.pylori  eradication for all H.pylori infections cases and what conditions people should or should not have H.pylori  eradication.

In the project, we are likely to learn how H.pylori affects human health related to Gastroesophageal reflux disease (GERD), Inflammatory bowel diseases (IBD), allergy, and asthma. I would think that the project will provide results which H.pylori infectious patients who have or do not have increasing effects of Gastroesophageal reflux disease (GERD), Inflammatory bowel diseases (IBD), allergy, or asthma after having H.pylori eradication. Also, what are differences in genomes or other factors which contributes to increasing of these diseases in the different group of patients who can be separated by ages, living conditions, and geography? The findings from the project which we likely to learn to play important role in future healthcare decisions because people will know which H.pylori infectious cases they should have H.pylori eradication and which one is not so as to prevent from gastric cancers. Also, for people who have Gastroesophageal reflux disease (GERD), Inflammatory bowel diseases (IBD), allergy, or asthma may have new treatments by using H.pylori bacteria. People can find categories for H.pylori infectious patients related to H.pylori eradication. Besides, the usage of antibiotic to stop and kill H.pylori would have the new approach to use in the right way.

Source: Blaser, M. J., & Falkow, S. 2009. What are the consequences of the disappearing human microbiota?. Nature Reviews Microbiology, 7(12), 887-894.

                The non-infectious diseases that I can think of are influenced by microorganisms are brain cancers, diabetes, heart disease, celiac disease, stomach cancer, Alzheimer disease, and Parkinson’s disease.                  

               Refer back to my writing #1, I was not sure what infectious diseases and noninfectious diseases are. I found that I understood wrong that all infectious disease would communicable. In the writing #14,  I was sure about my non-infectious diseases, and while I wrote down these diseases, I also thought of the relationship between microbe and human health. For example, IBD, including UC and CD is related to gut microbiota population. I think that the most important topics that I will take away with me once I have completed the course are the different microbes, as well as the diversity of microbes, plays the important role that can be beneficial or have negative effects on human health. There are many topics associated with the roles of microbes which the people need further studies to discover. People should learn how to improve the human gut microbiota which is significantly important. I would learn and earn more knowledge about microbes and try to find information for controversial and information which researchers are trying to explain through their studies during this course in the next microbiology classes.

 

Microbial communities in the body could influence brain and mental health states through signaling pathway. The production of the neurotransmitter serotonin in the cells in the gut which may affect the signaling in the brain via the systemic interaction between the gut and the brain. In the study of a biologics, Hsiao, the research examined how certain metabolites from gut microbes are related to body’s serotonin ( 5-hydroxytryptamine, 5-HT) production. The microbiota plays a significant role in regulating host 5-HT. The indigenous spore- forming bacteria from the mouse and human microbiota leads 5-HT biosynthesis which affects host physiology. The gut microbiota modulates the peripheral serotonin level of the host [1]. Besides, the intestinal microbiome can prompt immune cells to produce cytokine which influences the brain via signaling of other cell types. Another example is the production of butyrate of the microbes which is correlated with the activity of cells in the blood-brain permeability. The gut microbes break down the carbohydrates into short-chain fatty acids such as fatty acid butyrates which enhance the blood-brain barrier by tightening connections between cells [2].

Besides, the brain and mental states may also influence on the gut microbiota through changes in behaviors or release of neurotransmitter, hormones, and steroid. For example, the release of catecholamines and norepinephrine during stress into the GI may cause the dysregulation of the gut-brain axis via the changes in GI motility, the mucus secretion, and epithelial cells. These might lead to different gut diseases. Also, in the early maturity life in the animal, the stress increased the level of corticosterone production and inflammatory cytokines. The stress situation may cause the decrease of gut function related to changes in the microbial community and gut diversities. Moreover, the development of postinfectious irritable bowel syndrome is correlated to stress-related psychosocial factions which could be somatization, hypochondriasis, and neuroticism [3].

Overall, microbes and mental health states are linked together. From the people with ASD have IBD and other gastrointestinal problems. There are different abundances of microbial communities in ASD patients in the relationship with gastrointestinal diseases. In the case study of John Rodakis, his son showed improvement in the gut and behavioral autism after using antibiotic treatments. This suggested that the researchers would need to conduct more studies about different members of gut microbiota which are associated with autism and neurological states [4]. From the lecture this week, there are proposals about influences of microbes such as bipolar disorder, obsessive-compulsive disorder, post-traumatic stress disorder, schizophrenia. However, there are also many skepticisms about these proposals which make this topic become controversial. I think that whether microbial communities in the body could influence brain and mental health states or brain and mental health states could influence microbial communities in the body should depend on specific patient cases.

Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., … & Hsiao, E. Y. 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161(2), 264-276.

Smith, P. 2015. The tantalizing links between gut microbes and the brain. Nature.526: 312-314

Thakur AK, Shakya A, Husain GM, Emerald M, Kumar V. 2014. Gut-Microbiota and Mental Health: Current and Future Perspectives. J Pharmacol Clin Toxicol 2(1):1016.

Rodakis, J. 2015. An n= 1 case report of a child with autism improving on antibiotics and a father’s quest to understand what it may mean. Microbial ecology in health and disease, 26.

 

1. Can experiments detect differences that matter?

                     This question is important when researchers carry out experiments. In this part, the author first talked about profiling a microbiome which is able to categorize at the level of phyla, species or genes. The disadvantage is from criterion which researchers used the different ratio of bacteria to distinguish microbes. For example, if an experiment was used to characterize animal communities, based on the ratio between an aviary of 100 birds and 25 snails and the ratio between an aquarium with 8 fish and 2 squids,  both an aviary of 100 birds and 25 snails were identical with an aquarium with 8 fish and 2 squids. However, it was not right because of the differences in stains in the genes which each species contain. Later, the modern technology provides a better way for distinction when they were able to study more genes in a sample. Nevertheless, if the networks are not characterized well, the outcome to any specific object is hard. In addition, the ability to identify functional differences in related genes play the important role to understand the genes or networks. Also, genomes are poorly understood with clues which can be true or false. Therefore, an experiment can detect differences or not play a significant role for researchers to understand fully about the subjects, especially topic related to genomes.

2. Does the study show causation or correlation?

                       In this part, the author discusses how an experiment was conducted in two directions, inverse and reverse directions in order to know if the study showed causation or just correlation. It’s so important to question when interpreting scientific literature. For example a study about gut microbiomes and diet in a 2012 article which was proposed a causal relationship after conducting a study between the gut microbiomes of old people living in care homes and old people living in the community. Though the data and proposal were fit together, the reverse causality, the potential for poor health to alter the gut microbiome, was not investigated. The less active immune system and differences in the digestion of frailer people could lead changes in the microbiome. In this case, the conclusion about the causal relationship was not correct. Thus, I think that this question helps researchers to have the overview and come with an appropriate proposal.

3. What is the mechanism?

                   This question helps researchers to have a deeper understanding of the subjects in their study. When there was a correlation which can contain a causal relationship also. However, the researchers do not know what makes the relationships. With the modern technology, the researchers are able to identify functional elements, different taxa, and specific characteristics. The experiment can be done to define actions of elements in microbiome related to the biochemical activity. This contributes to making a study become more convincing.

4. How much do experiments reflect reality?

                    This question focuses on examination the reflection of experiments to the reality. For example, the study about gut flora and weight gain. The researchers did the experiment on germ-free mice which did not represent the natural state of animals and do not have healthy owing. Thus, the study did not include the responses in animals with flouring microbiomes related to different adaption between mice and their microbiomes and human. Thus, the result may not generalize. This question provides researchers about their subject choices and evaluation if the result from their study is suitable and able to convince people in public including general readers and scientists.

5. Could anything else explain the results?

                This question made me think of variables in a study. It’s necessary for researchers to think that there are other potential factors which could affect the results of their study and the way to analyze the data, make generate the hypotheses and evaluate the conclusion. For example, bacteria affects human but whether or not there are possible factors contributing to these effects. It is important to know about contributing factors in a study in order to make sure the results are not affected by these factors before coming to a conclusion.

               ** Overall, these five questions help the researchers to avoid hype. I think that question about the mechanism is the most helpful when discussing the controversy topic. As I understand, the controversy topic is from the disagreements among researchers on a topic. The researchers carry out different studies on the same topic, but they may have different results which may lead to opposite conclusions. For example, my final essay focuses on a question whether or not Helicobacter pylori eradication should be applied for GERD, Inflammatory bowel diseases (IBD), and allergy and asthma patients which researchers had different results from their studies to argue about this topic. The unclear part which was hard to explain the mechanism to support.

Source: Hanage, W. P. 2014. Microbiome science needs a healthy dose of scepticism. Nature, 512(7514), 247.

 

During the peer-review process, I recognized many interesting points. First, I was so confused about the audience of the assay who is in bio-health science but not an expert in microbiology. English isn’t my native language, and I don’t know whether some words that I don’t understand other student know them. The difference is the language difference. Thus, I tried to image and pretend myself as a student who was born in U.S. before I start the process. Second, I felt so interested in reading and critiquing other students’ essays. I found the different writing styles between two essays such as the way the organize their essays and the language they use and whether they prepare and take the time to write their essays. I might know how passionate the author put into their essay. I followed the rubrics and critique the essays. I usually ask myself and search information before I write down my responses. Somehow, I try to provide the authors the clear feedbacks and not unnecessary ideas so they can have better ideas to revise their essays. I used

I also compared the essays I do peer-review and my own essay to think of how to revise my final essay. There are differences among essays, and I think that doing peer-review for other students’ essays help me to know clearly rubrics and ideas how other student work on their essays in order to improve my ideas in my essay. I found out that I lack some points based on the rubrics, so I definitely need to work on that. Also, from the essays, I learn the character of this essay based on a controversial topic. One essay is so simple and doesn’t have the controversial topic. Another essay, the student works well on supporting the thesis but not against the thesis. So I think that I should try to make a balance between pros/cons paragraph. This essay has a controversial topic which student needs to have an overview of both sides of a topic then make their own stance. If the pros are so strong and long paragraphs, and the cons are so weak and short paragraph, then the essay seems not controversial. It’s because the students don’t need to convince them in order to make a stance. Thus, after the peer review process, I carefully check my topic to make sure its controversy.  Moreover, I also learn about the tone and language. As the audience in bio health science but not an expert in microbiology, when I read the essays, I thought of my essay if I was the audience. Then I had many ideas how to change my language to be more suitable for the audience.

The process of the peer reviews is a process that is designed to review the validity and quality the originality of articles for publication. The peer review process stops the substandard and poor science so as to save time and money from publication. The reviewers are experts and have updated developments in their fields in order to evaluate and reject the plagiarized and duplicate papers. Besides, the peer review process can be used to publish the journal and to apply for the grant and standard textbooks. The process is also to increase the integrity of science.

                    However, the peer review is also related to some disadvantages. There may be criticism related to human activity based on perceived faults or mistakes. Editors are the connectors between the author and referee, and the editors have decision-making power. These can lead to the misuse of authority. Because there is no grading system in the peer-review process, the different journals have different standards in order to know the expertise and quality of the reviewers or editors. Besides, the peer-review process is time-consuming and expensive. The length of time in the peer-review process, many months is before the manuscript is approved. If the researchers have experiments to do, the process may be delayed and hampered. These disadvantages affect the credibility of the results of the process of peer-review.  

                      The process of peer review has five steps which start at the submission of paper and end at the communicated decision (no revisions required for publication in the journal). The authors need to write up all information for a draft manuscript such as the relevant data, methods, observations, and discussion. Then the first step of peer review process is to submit the manuscript based on several factors including subject matter, the concern of researchers, the chance of earning funding, and connection of authors and editors. The second step is editorial office assessment. The editors check the compositions of the paper such as the focus on the clinical research, exciting research, and solid foundational research in order to make an initial decision. Based on journal’s philosophy and journal’s author guidelines the, the editors will reject the manuscript outright, so the authors need to submit their manuscript to another journal. If the editors accept the manuscript, the manuscript will get into step 3. The third step is to review the manuscript by 2 to 4 reviewers. The reviewers who have done researchers in fields related to manuscripts are chosen by the editor. The reviewers are anonymous to the authors, but the authors do oppositely. The reviewers read and evaluate the manuscript for scientific merit. The reviewers are usually based on questions such as the relevance of the question of the manuscript, the clear of the hypothesis and model, the manuscript is primary research or clinical research, and the support of data and analysis of data for the manuscript. The reviewers then summary their thoughts and evaluations. The reviewers will write a letter about their responses such as their concerns of a figure-by-figure breakdown to the editor, abstractions about the manuscript, and their recommendation for the editor whether the manuscript would be accepted or rejected. The fourth step is editor assessment of reviewers. After the editor receives the feedback from the reviewers, there are three things the editor can choose to do. First, they accept the manuscript without revision requirement. Second, they reject the manuscript. Or the third thing is to send the comments back to the authors for further revision of the manuscript. The editor will send a letter to the authors with their decision and comments. The fifth step is author’s revision. In case, the author revises their manuscript, they can contact to editors to announce their changes in the manuscript to solve the criticism. Then the author resubmits their manuscript and goes through the process of peer review again.

 

1. Hand hygiene: practicing hand hygiene is a helpful approach to prevent bacterial infection. Hand hygiene is used to prevent the spread of germs due to killing all of them. People can use soap and warm water to clean their hands before touching and/or after using the bathroom, taking out the trash, changing a diaper, visiting someone who is infected. It’s good to make sure to wash hands after sneezing or coughing.
2. Clean high-traffic objects in home and office: In order to reduce the number of bacteria in our environment, people should keep certain objects which people and others in their household use regularly such as door knobs, toilet handles, telephone, and bathroom. Disinfectant should be used to wipe to clean the high-traffic objects once a week
3. Steer clear of anyone who seems sick: People should avoid contacting close to anyone who seems sick and touching people who are infected, people who have the flu or contagious illness.
4. Stay informed about food and water recalls: It’s important to stay informed in order not to ingest contaminated water or food. Food contamination is a common issue. People can listen to the local news about contamination food and water supply. If there is the situation of food and water contaminated, people should purchase water bottle to drink and not to take shower. Staying informed about food and water contributes to protecting yourself from foodborne bacteria.
5. Wash and cook food well: Washing and cooking food well can help to prevent bacteria from entering to digestive systems. All fruits and vegetable should be washed before consuming. All meat and fish should be cooked thoroughly to any harmful bacteria. People also should avoid eating raw or undercooked meat and eggs. Besides, people should use their own utensils.
6. Take steps to reduce the risk of developing vaginitis, an inflammation of the vagina and/or vulva from bacteria, chemical irritants, or viruses. people shouldn’t douches in order not to change to pH of the environment in the vagina and to decrease the risk of the bacterial infections. Also, people should have one sexual partner and shouldn’t smoke due to association with risk of developing a bacterial infection.
7. Vaccination: Getting vaccinated is a way to against bacterial infections. Bacterial vaccines are able to kill bacteria. Antibodies can against particular bacteria and prevent bacterial infections later. Some form of vaccines such as Tuberculosis vaccine and vaccines to against meningococci, pneumococci, and enteropathogenic E. coli.
8. Mode of delivery: The vaginally born infant have diverse microbial community compared with the C-section born infant.

 

1. Diet: Pregnancy imposes changes in the bacterial composition of pregnant women. In the article “Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother’s periconceptional diet”, the authors did a study about diet and pregnancy interaction, high-fat diet intake before and during pregnancy leads typical shifts in the pregnant gut microbiota. This causes the major differences in the abundance of genes related to lipid metabolism, gluconeogenic and glycolysis metabolic pathways during pregnancy period. In the infants, the transition from milk to solid food changes in their microbial population and species. The infant’s gut microbiota has an abundance of Bacteroidetes and Firmicutes same as adults’ microbiota [4].
2. Antibiotic use: the antibiotic use cause change in maternal microbiota and abundance of some taxonomic groups. The use of B antibiotic including azithromycin, amoxicillin, and cefaclor triggers the increase of Proteobacteria and Enterobacter and decrease of Firmicutes and Lactobacillus [1]. Besides, similar effects with normal people, antibiotic contributes in reducing bacterial diversity in the gut microbiota of pregnant women. Antibiotic also causes weight gain [4]
3. Probiotic use: the pregnant women who used probiotics 14 days before C-section showed modulation of the infant microbiota as well as offspring’s microbiota. The probiotic treatments on pregnant women gave advantages to the offspring to have the immune system to respond to pathogens and commensal after birth and reduce the risk of eczema as well. The immune modulation affects the microbial components.
4. Mode of delivery: The gut microbiota of infants has a relationship with mode of delivery [3]. The gut microbiota of vaginally born infant is colonized by bacteria from maternal vagina including the enrichment in the Prevotella, Sneathia, and Lactobacillus group which is a positive factor to infant microbiota [2]. The infant born by C- section has delayed colonization of the phylum Bacteroidetes and alpha diversity during first 2 years of life. Also, the infant born by C-section has higher number of antibiotic-resistance genes compared with infants born vaginally [4]
5. The method of infant feedings: There are differences in gut microbiota between breastfed infants and formula-fed infant. The major organism in breastfed infant is Bifidobacteria while the formula-fed infants have Enterococci and Clostridia mostly. Besides, the breastfed infants have more bacterial cells and less species diversity. The methods of feeding have effects on infant’s oral microbiome also. The study shows that the three-month-old breastfed infants consist of oral lactobacilli with antimicrobial properties which didn’t appear in formula-fed infants [4].  

Sources:

1. Gonzalez-Perez G., Hicks A. L., Tekieli T. M., Radens C. M., Williams B. L., Lamouse-Smith E. S. 2016. Maternal antibiotic treatment impacts development of the neonatal intestinal microbiome and antiviral immunity. J. Immunol. 196, 3768–3779. 10.4049/jimmunol.1502322
2. Jakobsson H. E., Abrahamsson T. R., Jenmalm M. C., Harris K., Quince C., Jernberg C., et al. . (2014). Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 63, 559–566. 10.1136/gutjnl-2012-303249
3. Khan I., Azhar E. I., Abbas A. T., Kumosani T., Barbour E. K., Raoult D., et al. . 2016. Metagenomic analysis of antibiotic-induced changes in gut microbiota in a pregnant rat model. Front. Pharmacol. 7:104. 10.3389/fphy.2016.00104
4. Sela D. A., Li Y., Lerno L., Wu S., Marcobal A. M., German J. B., et al. . (2011). An infant-associated bacterial commensal utilizes breast milk sialyloligosaccharides. J. Biol. Chem. 286, 11909–11918. 10.1074/jbc.M110.193359

I read through the syllabus in order to understand the final essay. The first word came to my mind is a controversial topic. It’s interesting to think of controversial topics related to the microbiome. My first thought is microbiome species, similar to biological species when I searched the definition of microbiome at beginning of the class. I found that this controversial topic brought researchers different areas and classifications for microbiome species concept (MSC). Another topic is the relationship between microbiome and disease. Researchers have been studying whether the variant microbiome are from responses of human to environmental factors or through heriterity. The variant microbiome caused disease related to immune responses in beginning to cancer period, local microenvironment, or potential inflammations. Also, the topic about the role of Helicobacter pylori in the pathogenesis of gastric reflux esophagus disease (GERD). I’m curious why eradication of H.pylori doesn’t induce in these disorders, and whether or not, antibiotic treatments work perfectly for these diseases. The “ commensalisms” suggested that eradication the H.pylori causes the worse GERD and asthma. However, H.pylori infection can lead to gastric cancer. So whether or not we should kill all H.pylori or just restrict their growth in symptomatic or nonsymptomatic individuals.

I have three topics including classification of the microbiome, the role of the microbiome in disease, and eradication of H.pylori in symptomatic or nonsymptomatic infected people related to GERD. I try to remind myself about classifications about microbiome, but I don’t have a lot of ideas about this topic. So, I start to consider about the classification of microbiome and H.pylori. Also, the variant microbiome is a new topic to me. I read the information about microbiome which is a combination of genetic material and influences of environmental factors. But How microbiome change? What trigger their changes? Besides, I did my midterms about H.pylori topic, and at that point, I focused on what is H.pylori, how people gets infected, and how treatments work in H.pylori infections. I understood about H.pylori had all negative effects and side effects from H.pylori treatments using antibiotic. However, now I’m going to work on a controversial topic about H.pylori. It sounds cool to debate myself about H.pylori. Maybe, it changes my perspective about H.pylori infections in different ways.

I think that my final essay will cover eradication or preservation of H.pylori. It’s interesting to turn my mind up and down sides about H.pylori. I may start my essay from outlining the organization of my paper such as discovery and characteristics of H.pylori related to how H.pylori affects human health, the idea of eradication of H.pylori (pros/cons), the preservation of H.pylori, and my standing side at the end. I will build my introduction, body paragraph according to ideas above, and conclusion. First, I will read again the articles which I found for my midterm and selected which one I would use for the final. Then I continue to find articles about H.pylori infections, eradication treatments, and preservation of H.pylori. I will underline main findings, howe researchers conducted their studies, and information support for my ideas also. Then I will put the information into my outline. Finally, I will write and build a completely paragraphs.

In my country, most patients are provided antibiotics when they get sick including cold, flu, sore throat. This has made my philosophy about antibiotic as a common medicine for these diseases which is wrong. When I was 18, I got a strep infection caused by streptococcal bacteria. My classmate spread the strep infection to me because I sat next to her. At the beginning, I thought that she got some common coughs. The infections made my throat and tonsils irritated, swollen, painful, and inflamed without coughing. My mouth had some road spots, and I had a hard time to swallow food. I didn’t go to any doctor and waited to recover by drinking water, but my situation got worse. Later, when I met a doctor, he said that I got strep infection, a kind of bacterial infections. He recommended me to use antibiotics such s penicillin, cephalexin, and amoxicillin, for I got many days in being infected. I asked him about the antibiotic, and he explained to me different situations for use of antibiotics which treat only infections caused by bacteria, not any viruses. And people shouldn’t use antibiotic for cold and flu if they are from viruses. Also, bacterial resistance becomes harder to treat if people use antibiotic too often or wrong way. I followed exactly my doctor’s instruction in taking antibiotic, and I recover around 2 weeks later. From that point, my philosophy about antibiotic change completely which antibiotics are used to treat specific infections from bacteria. It was so interesting to learn about antibiotics and how to use them wisely and usefully.