The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
1. Host-Gut Microbiota Metabolic Interactions. Nicholson. Science, 2012.
ReplyDelete2. Gives an introduction to the importance of the microbiota in human physiology. Also covers the changes with age and other facts without delving into too much depth.
3. Recommend reading. The paper does a good job of highlighting just how important the microbiota is. Also, it elucidates the directions future research should/may take.
1. Microbial Genes, Brain & Behavior - Epigenetic Regulation of the Gut-Brain Axis. R. M Stilling. Genes, Brains, and Behavior, 2014.
ReplyDelete2. This paper discusses the impacts of the microbiota on behavior and neurology, including neuronal makeup. In addition, it considers the microbiota as a separate epigenetic entity and discusses its development and hereditary nature.
3. Worth reading if we choose to focus on the microbiota's hereditary characteristics.
I also read the Stilling paper.
DeleteThe definitions in this paper were very useful. They did a good job explaining basic epigenetics terms such as microbiome, probiotic, and enterotype. Most of the terms were new to me. It is a really good overview of epigenetics of the gut-brain axis with good examples. I think it would be worth having a group present on this paper because it relates genetics to diseases such as depression, autism, and irritable bowel system, and I know in class we discussed that we wanted disease to be a part of our gut-brain axis review. I would like to be part of a group that presents on this. The paper discussed the environment affecting disease, and the review paper I read on Parkinson's disease and the gut-brain axis also discussed environmental factors.
1. The gut-brain axis: interactions between enteric microbiota, central, and enteric nervous systems. Carabotti. Annals of Gastroenterology, 2015.
ReplyDelete2. This paper explores how the gut-brain axis has bidirectional communication between central/enteric nervous systems. It glosses over how dysbiosis of the microbiota in the gut is often associated with central nervous disorders like autism.
3. This paper is worth reading if you want brief overview of the role of microbiota in influencing mood disorders, the adrenal/pituitary/hypothalamus axis, and behaviors related to anxiety, stress, and depression. The paper doesn't go into in-depth molecular mechanisms, however, and only presents brief descriptions of the role of microbiota in modulating Gut brain axis.
1) Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Stilling, et al. Genes, Brain and Behavior (2014)
ReplyDelete2) This review discusses the gut microbiome's potential role in behavior, development, and neural pathology. They talk about evidence to-date of a person's enterotype (microbial species composition) correlating with mood and behavior as well as potential contribution to developmental disorders such as ASDs. They mention a number of studies that used germ-free (GF) mice, which are completely void of bacterial colonization from birth, to assess the brain-gut-microbiome axis (which they lump together in this paper). It has been shown that molecular and behavioral phenotypes in GF mice are reversible by probiotic treatment. They also talk about gene-environment interactions and how the gut microbiome can play a direct and indirect role in the epigenetic response of host cells to environmental changes.
3) I think it's pretty clear that we can't build a model of the gut-brain axis without the microbes -> gut-(microbiome)-brain is more like it. However, it's also clear from this review that research into the gory details of the molecular mechanisms for microbial impact on epigenetic regulation in the host is still in its very early stages. This paper calls attention to this system as a whole, and would be a great jumping-off point for a deeper dive, since there's five pages of references to prior related/tangential research.
I agree with Louis and Cody that this paper was an interesting read. I don't know too much about current attempts to model gut-brain axis on a chip or if any attempts have included the microbiome in these models. If there have not been any attempts to include the microbiome into these models, I think people in charge of the gut-brain axis on a chip section of the final report might find strong arguments on why it is essential that we include the microbiome (or some aspect of the microbiome) in our model based off this paper.
DeleteI really liked the tables and figures in this article (especially Table 1 which outlines behavioral effects of different microbiome compositions). I also definitely agree with the above comments that this article helps showcase the need to more fully integrate the effects of the microbiome into our model of the GBA.
Delete1. The interplay between the intestinal microbiota and the brain. Collins. Nature Reviews, 2012.
ReplyDelete2. This paper presents an in-depth analysis of the various components of the gut-brain axis, specifically through exploring the enteric nervous system, central nervous system, immune system, endocrine system, and the microbiota (and how they all interact). This paper also presents much biochemical evidence for each of the pathways between each node of the gut-brain axis.
3. Phenomenal paper if you want to gain a strong understanding of the physiological and biochemical basis of the overall gut-brain axis. It very clearly outlines each part of the GBA, great figures, and also shows applications to psychological/physiological diseases and how the GBA causes/regulates them with potential therapeutic applications.
I also liked this article. It gives a good introduction to the interplays between the brain and the microbiota. Importantly, it discusses the actions of the brain on the microbiota, something the other articles I read did not cover so well. In addition, it does a good job of mentioning the limitations of current research, such as using mouse models. Lastly, the discussion of brain development and microbiota was something I had not seen before.
DeleteThis is a good one. Provides a pretty detailed map of biochemicals necessary for different parts of the brain and how and where they are created/metabolized along the gut brain axis, including the names of key players in the microbiome. Much of this paper is focused on behavior and brain development, but the contents could provide specific inputs/outputs/parameters for rough models of biochemical pathways in the GBA.
Delete1) Pathogenesis of Parkinson disease - the gut-brain axis and environmental factors, Lisa Klingelhoefer, Nature Reviews, 2015.
ReplyDelete2) Parkinson’s disease has many nonmotor symptoms including gastrointestinal problems like constipation. Parkinson’s disease risk factors includes many environmental factors (such as pesticides and metals), leading to a new hypothesis that this disease emerges in the enteric nervous system (ENS) and spreads to the central nervous system (CNS) through the sympathetic and parasympathetic nerves.
3) We will be having a short presentation on Parkinson’s disease in the future, so I think that will be useful for the class if it focuses on the gut-brain axis as it relates to this disease. I don’t think the class necessarily needs to read this paper, but the person/people assigned to diseases of the gut-brain axis might find this useful.
Another potential companion piece to this paper is Anthony Schapira et al.’s paper “Non-motor features of Parkinson disease” published in Nature Reviews: Neuroscience in 2017. I think this paper has some figures that could be useful for the final report in addition to the assigned paper’s figures. Furthermore, Kalia and Lang’s review “Parkinson’s disease” published in Lancet in 2015 has a useful figure of when different symptoms of the disease appears (with gastrointestinal symptoms appearing long before the motor symptoms, and Braak et al.’s paper “Stages in the development of Parkinson’s disease related pathology” published in Cell and Tissue Research in 2004 contains a figure with the Braak stages that was mentioned in the assigned article (in case people are not familiar with system).
I agree that this paper will be useful in the future. I can see it as being a good introduction to PD and how it relates to the GBA.
DeleteKylie - Will you present summaries of these new articles, or do we need to add them to the scan list?
DeleteI present some summaries, but I might not have time to do it before today. I can at least gather some of the interesting figures from these papers into a powerpoint.
Delete1) The Interplay of the Intestinal Microbiota and the Brain, Collins, 2012
ReplyDelete2) Overview of gut-brain axis and difficulties in mouse studies on discovering the mechanisms of the microbiota.
3) It gave me a good idea of what physiology I need to study more...I have a general understanding of the central and peripheral nervous systems but not the biochemistry that was discussed. It had a lot of helpful definitions of various physiological terms such as parts of the brain.
From what I saw with the article, it seemed very involved. I think it will be useful but probably not the best to start things off with. Perhaps we could have a group try to tackle this article for a group presentation.
DeleteWe need to consider the mouse as a model for on-chip models. What is done to study the mouse, and what might this tell us about how to build and test a human gut-brain chip model?
DeleteI agree with both Danielle and Kyle. This paper presented a solid overview of the gut-brain axis and its components. The paper does delve into very deep biochemistry and the molecular mechanisms of the GBA, which makes it pretty lengthy to read. However, I still feel that the figures and overall flow of the paper is very structured and well-written and can provide a good idea of not just the definition of the GBA but also how each component interacts to truly create a network.
Delete1) Gut Microbiota: The Brain Peacekeeper, Mu, Frontiers in Microbiology, 2016.
ReplyDelete2) It's a great overview of interactions between the gut microbiome and the brain (specifically cognitive function, behavioral regulation, ciradian rhythms). It includes a section on epigenetic regulation of neuronal cell function and a section on the implications of the microbiome on the gut-brain axis, so it lines up really well with what we've been talking about.
3) I would definitely recommend that we read specific sections, but probably not the entire article.
I agree with your sentiment. The article stood out to me since it discussed circadian rhythms but it very much is just an article for reference.
DeleteWe need to decide which sections to include
Delete1) The Microbiome-Gut-Brain Axis in Health and Disease, Dinan, Gastroenterology Clinincal, 2016
ReplyDelete2) This paper is basically a short review of how the M-G-B axis is a player in a few diseases, such as Parkinson's, autism, and depression. It hopes that the literature will build off of the role of the M-G-B axis in IBS to be used in other diseases.
3) The best future action would be to look into some of the references and see if any of those provide any more detail
I agree with your point that this paper doesn't provide much detail into the actual gut-brain axis. This paper is worth glancing at to get a glimpse of some disorders that are grounded in the gut-brain axis, but it does not provide very good figures to develop the holistic framework of the gut-brain axis and the various biological systems at play
DeleteWe should probably prepare a list of diseases with references
Delete1) Mind-altering microorganisms: the impact of the gut microbiota on brain and behavior. John F. Cryan. NATURE REVIEWS NEUROSCIENCE. 2012.
ReplyDelete2) This paper is comprehensively summarized how gut microbiota influenced behavior and its contribution to CNS disorders (pain, autism, obesity and multiple sclerosis). It specifically listed studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs, which suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain.
3) One of drawback of this paper is that it is unclear about how various gut microbiota strains deferentially affect behavior. I’d recommend treat this article as a preliminary inventory for studies on gut-brain axis vs behavior. Also some of its experiments are noteworthy.
Please expand your discussion of noteworthy experiments!
Delete1) The Central Nervous System and the Gut Microbiome Gil, Gil Sharon, Cell, 2016. 2) A very intriguing idea is presented here and is also touched by some of the other papers above. The gut bacteria is a key player in the development and function of the nervous system. 3) This review paper is definitely worth a quick scan but it may not provide much of details that one looks for.
ReplyDeleteWe clearly need to understand more about the relationship between gut development and brain development! Suggestions as to how we might proceed?
DeleteI
ReplyDelete1. G.Dinan_2017_The microbiome gut brain axis in health and disease
2. This paper serves as an introduction to how IBS can induce CNS diseases. It is a good starting point but the figures are only okay.
3. Considering the emphasis of PD in our group, we may want to focus on a paper that is more focused on PD, like Klingelhoefer et al.
II
1. Carabotti 2015 The Gut Brain Axis Interactions Between Enteric Microbiota,Central And Enteric Nervous Systems
2. This paper didn't stand out. The main figure is bland compared to the other articles. Table 1 seems useful since it consolidates interactions for the GBA.
3. This seems like a nice paper to skim through but discussion will not be needed.
III
1. Cryan_2012_Mind Altering Microorganisms
2. This paper has great figures and discusses potential mechanisms for GBA and how it relates to CNS diseases.
3. This paper is old compared to the other papers (2012). The figures will be good for presentations but we shouldn't focus on this paper since it is dated.
IV
1. Stilling 2014 Microbial genes, brain & behaviour – epigenetic regulation of the gut – brain axis
2. This article discusses the epigenetics involved with GBA interactions and refers to many articles which are examples of good and bad interactions. They also have a table with definitions which is nice.
3. This paper will be crucial if we want to relate the epigenetic landscape to the GBA. This a good starting point for that discussion since it explains things well and discusses the epigenetics of the GBA.
V
1. Nicholson_2012_Host Gut Microbiota Metabolic Interactions
2. The main figure is too busy and hard to interpret. The table with metabolites seems useful if we want to investigate metabolites associated with the GBA.
3. The most useful thing with this paper is the table of metabolites. This paper seems like a good reference but not worth a full discussion.
VI
1. Collins_2012_TheInterplayBetweenTheIntestinalMicrobiotaAndTheBrain
2. This paper gives an overview of the GBA but doesn't go into the disease component. It has great figures and appears to explain things thoroughly.
3. Could be worth a class read but at the very least should be presented by either someone or a small group. A worthwhile paper but since it is from 2012, we will need at least one additional paper to go with it, especially if we want to emphasize CNS disease or epigenetics.
VII
1. Mu_2016_GutMicrobiotaTheBrainPeacekeeper
2. This paper has really bad figures. The paper discusses how microbiota interact in the GBA and introduces the idea of circadian rhythm modulation. It also discusses epigenetics.
3. This paper should be read as a class but is useful as a reference for the interactions of microbiota.
Correction on VII: 3. I meant to say that it shouldn't be read as a class but could be a useful reference.
DeleteExcellent analysis. We need to figure out how to transfer this type of analysis to the master list.
DeleteVIII
ReplyDelete1. Schroeder_2016_SignalsFromTheGutMicrobiotaToDistantOrgansInPhysiologyAndDisease
2. This paper explores how other organs affect the GBA. It has good figures and a good table that consolidates the mechanisms for interaction with different organs.
3. This paper will be useful if we want to consider the far reaching effects of the GBA beyond the gut and brain. Perhaps a good article for arguing to have a complex microphysiological system to model the GBA.
IX
1. Wells_2016_HomeostatisOfTheGutBarrierAndPotentialBiomarkers
2. This paper discusses the biochemistry involved with homeostasis in the gut. The figures and tables are detailed and well drawn. The article appears to be involved so it will be difficult to parse through initially. ]
3. This article should not be read as a class as of now but could be read in the future. The most likely thing that will happer is a small group will present this article to the class considering how involved it appears to be.
X
1. Sharon_2016_TheCNSAndTheGutMicrobiome
2. Discusses CNS diseases and how the Gut microbiome develops in a lifetime. The figures are good and there is discussion about some of the mechanism.
3. Probably not worth a full class read. Worth a scan by people working on the disease side of the project.
XI
1. Klingelhoefer_2015_PathogenesisOfPDTheGBAandEnvFactors.pdf
2. This paper discusses how PD is related to the GBA. It has good figures and appears to be a good introduction to the topic.
3. Should be presented at some point, potentially read as a class. At the very least, the disease people should present it.
Good analysis. I've added a page to our Google sheet so that you and others can transfer the analyses to a central location.
DeleteI also read the Wells paper.
DeleteI agree with Kyle in that it is very involved. It would be difficult to break down together as a class. It is very detailed and has a lot of useful information, but would take too much time to go over as a class and would be better for a small group to present. The pathways discussed are very interesting though...I would love to present it and read it more thoroughly with a classmate who is more knowledgable about biochemistry than me.
Here are my rankings for the papers:
ReplyDeletePotentially read as a class:
IV: Stilling 2014 Microbial genes, brain & behaviour – epigenetic regulation of the gut – brain axis
VI: Collins_2012_TheInterplayBetweenTheIntestinalMicrobiotaAndTheBrain
VIII: Schroeder_2016_SignalsFromTheGutMicrobiotaToDistantOrgansInPhysiologyAndDisease
XI: Klingelhoefer_2015_PathogenesisOfPDTheGBAandEnvFactors
Presented as by subgroup on the topic:
VII: Mu_2016_GutMicrobiotaTheBrainPeacekeeper
IX: Wells_2016_HomeostatisOfTheGutBarrierAndPotentialBiomarkers
The rest are worth a scan if it is realated to your task but not for direct presentation of the article.
Excellent - we will discuss on Thursday!
Delete1) The Microbiome-Gut-Brain Axis in Health and Disease. Cryan. Gastroenterology Clinical. 2016.
ReplyDelete2) This paper provides a very brief, introductory summary of the gut-brain axis. It then delves into the biochemical/mechanistic pathways of specific disorders like Depression, autism, and Parkinson's Disease. It also provides an interesting blurb on psychobiotics and how they can influence positive mental health.
3) This article is worth a scan but does not provide a very good holistic framework of the entire gut-brain axis, but rather just presents short examples of studies that examined it. However, I personally liked Figure 1 a lot visually.
I think we need to create a Google Slide set with the best images, each with citations.
Delete1) Signals from the gut microbiota to distant organs in physiology and disease, Schroeder, Nature Medicine, 2016
ReplyDelete2) This paper is interesting in that it discusses the role of the intestinal microbiome in a number of associated diseases and physiological changes, and also works backwards from a few less associated diseases to suggest potential involvements. The microbial "signals" the paper discusses are mostly metabolic products, derived from flora in conjunction with diet and host factors, and references to the systemic effects of these metabolites are throughout. The role of short chain fatty acids is discussed the most. It also spends a lot of time going back and forth between mouse and human studies, which is helpful in some regards but it's important to remember that not every interaction in mice will have an equivalent human counterpart.
3) Much of the primary info can be scanned in figures, specific metabolites are mentioned and can be searched out if needed; Caleb's section on disease may benefit from a look.
I checked out this paper and also feel like this paper is a really good read on how the microbiome specifically takes in chemical and environmental signals and produces metabolites/signaling molecules that communicate with distant organisms. This paper also examines the specific role of gut microbiota on specific physiological and psychiatric disorders. While the paper does not go in-depthly into non-microbiota players in the gut-brain axis besides microbiota, the figures in this paper are definitely noteworthy. I think Figure 4 is a really good visualization of a mouse model for the GBA. Table 1 is a good summary of how the microbiota communicate with organs.
DeleteI’d like to suggest another potential reading for the class.
ReplyDelete1) Gut feelings: the emerging biology of gut-brain communication, Emeran A. Mayer, Nature Reviews: Neuroscience, 2011.
2) This article talks about gut-to-brain signaling during homeostasis and when homeostasis is disturbed. It goes through immune-related signaling, endocrine and paracrine signaling, and neuronal signaling, as well as how the gut and brain can affect one another.
3) It’s a bit of an old review at this point, but I thought it was a nice overview of the gut-brain axis and had some nice figures. It’s a pretty dense review though, so it might take some time for everyone to get through it.