Friday, November 27, 2015

I am taking antibiotics but I do not have an infection




            In science, the benefits gained from the symbiotic relationship between microbiota and their human host is not debatable. Yet, the microbiota’s roles in nutrient absorption which leads to obesity just recently start to unravel. There are two types of fat in mammals that function in the opposite manner: brown fat (or beige fat) - heat production, insulin sensitivity and obesity reduction while white fat - energy storage, insulin resistance and obesity. During exercise or being cold, human body will start a process called “browning” where the beige cells start to grow within white fat and burn the calories to produce heat and energy. Researchers at the University of Geneva did a study on mice where they were put into three separate groups: germ free, standard (control) and microbiota-depleted (previously treated with high doses of antibiotics). They were all fed with high calorie diet. Results indicated that control mice developed obesity and insulin resistance while the germ-free and microbiota-depleted mice did not. They also observed an increase in white fat and decreases in brown fat in the control.

            What is the implication and how does it work? Macrophages, essential immune cells, also function in many metabolic processes such as tissue remodeling. In the depletion of microbiota, eosinophils produce type 2 cytokines, signaling proteins, to signal macrophages to activate the browning process which results in reduction of obesity. This became obvious that microbiota contributes to obesity; yet, it is not realistic to treat obesity with high dose antibiotic let alone the tremendous benefits that our bodies gain from the gut microbiota. This has created new opportunity for researches in identifying the specific strand of gut bacteria that cause obesity as well as the possibility of transferring microbiota from lean to obese as future treatments. 


Source: http://www.news-medical.net/news/20151117/Scientists-show-how-absence-of-microbiota-has-remarkable-effect-against-obesity.aspx

3 comments:

  1. Khoa,

    This is a cool find and a very interesting topic. It reminds me back of the good 'ole days of BL610A when we where discussing the microbiota's role in patients with C. dificile and how fecal microbiota transfer could be a rather effective solution.

    It appears that this topic of one's microbiota is rather "hot" in terms of research and it appears that results are all over the place currently. In The Lancet of Infectious Diseases, Dixon addresses the same issue. However, his mentioned results that he discusses are the opposite. He and some professional colleagues argue that the presence of microbiota, just in different forms, actually help reduce obesity. The basis for such a claim stems from him believing that certain bacteria actually ferment normally non-digestible carbohydrates as well as alter expression of peptides responsible for adipose formation.

    As a result, much research remains. Questions left to be answered include:
    1. Does quantity of gut microbiota affect obesity, and if so, how?
    2. Does composition of gut microbiota affect obesity? If so, which bacteria specifically contribute to obesity and which bacteria counteract it?
    3. Does more than one combination of the factors from #1 and #2 contribute to a physiological phenotype?

    I think the future has some interesting results ahead of us. I'm very curious to see what conclusions, if any, can be agreed upon by many.

    Great job, Khoa!

    Cited Source:
    Dixon, B. (2010). How do gut bacteria affect obesity? The Lancet Infectious Diseases, 10, 372-372.

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    Replies
    1. Hunter,
      Thank you for your comment. I'm actually not surprised when there exists other researches that are contrary to this particular topic. We learned this very well as we conducted our research on gingivitis in BL619, it is the nature of science right? I'm also interested in whether dietary habits can potentially affect the microbiota's composition. I ran across an abstract addressing this concern briefly where there is an elevation of Bacteroides in protein/fat diet versus Prevotella in high carbohydrate diet. I'm sure there is a lot of room for future researches.
      Great comment Hunter!
      Source: http://www.sciencemag.org/content/334/6052/105.full

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  2. This was an interesting article! Decreasing obesity and increasing brown fat by using high doses of antibiotics seems like situation where the ends do not justify the means, the affects of germ free microbiota depletion seems much worse than any benefit from increasing brown adipose tissue. But none the less interesting how lowering microbiota influence the percentage and composition of adipose tissue white vs brown. There has been a lot of work on how to increase gut microbiota via the diet but how diet actually changes the gut microbiota would be interesting to understand more clearly.

    The use of macrophages is something interesting that is being used more and more in research. Working in diabetes research at Anschutz I have used macrophage conditioned media on human skeletal muscle myotubes as a way to understand pro-inflammatory markers such as TNF-alpha , IL-6, and IL-1beta and how their activation and release leads to other deleterious effects in insulin resistance. Also using macrophage conditioned media along with different treatments to see if the negative affects can be mitigated.

    The idea of transferring microbiota from lean to obese people seems like a great concept, from what we have previously discussed in class and in TBL the complexity and importance of the diverse gut microbiota is vital and related to all kinds of diseases. There has been several papers discussing this, and showing very successful results in mice. The introduction of gut microbiota from control mice into germ free (high antibiotic dosage) resulted in a 60% increase in body fat and insulin resistance within two weeks despite reduced calorie consumption. The transfer of the microbiota harvested from obese mice (ob/ob) into germ free mice caused the transfer of the obese phenotype.

    My questions about this relates to what specific type of organisms in the gut are closely related to obesity? And is there a interplay and “communication” between the gut microbiota that leads to a more susceptible environment for diseases. Or is it how the gut microbiota influences the production or transistion from white adipose tissue to brown adipose tissue that influences obesity more significantly? More specifics on what species and what densities would be interesting to know, but perhaps hard to determine as everyone is different and the diversity within the microbiota is more important than say one specific organism.


    Yu, Junna. Shi, Lihuan. Wang, Hui. Bilan, Phillips. Yao, Zhi. Samaan, Constantine. He, Qing. Klip, Amira. Niu, Wenyan. (2011). Conditioned Medium from Hypoxia-Treated Adipocytes Renders Muscle Cells Insulin Resistant. European Journal of Cell Biology. http://www.sciencedirect.com/science/article/pii/S0171933511001269

    Backhed, Fredrik. Ding, Hao. Wang, Ting. Hooper, Lora. Koh, Gou. Semenkovich, Clay. (2004). The Gut Microbiota as an Environmental Factor that Regulates Fat Storage.

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