A Research Idea

I was doing my rounds reading some of the great blogs I follow and came across one topic I am really starting to appreciate, the importance of our gut physiology. 

My real love and curiosity is related to optimum physiological functioning arising from primary and secondary holistic preventive methodologies. This goes well beyond nursing and includes a variety of scientific disciplines and causeways. The connection to nursing is often opaque and unrefined, even though the relationship is stronger than we realize.

One clinical problem requiring greater understanding are the long-term implications antibiotics have on our immunity, metabolism, and disease progression. This is not generally considered, since antibiotic use is standard practice and routinely administered prophylactically and for nonemergent circumstances. I am not implying they should not be used. The salient point here is not their short-term benefit, rather their long-term implications.

This type of study would be observational in nature, reviewing decades of antibiotic administration and bowel disorder data. It could take on meta-analysis like characteristics. Factors affecting feasibility would not include cost since the study could follow current and past administration of an antibiotic use. The focus could be narrowed to ciprofloxacin since it is considered one of the most benign perturbative antibiotics (Dethlefsen, Huse, Relman & Sogin, 2008). Pooling available data would generally require just the researcher’s time.

Further narrowing the focus: identifying previously known perturbations antibiotics play on our gut flora may elucidate implications with gastrointestinal disorders such as celiac spree, inflammatory bowel disease, and Crohn’s disease. Feasibility of the implications applies to the type of practicing clinician. How preventive and holistic a practitioner may be may determine the research’s applicability. From an integrative or holistic perspective, this information can provide significant implications for treatment.

Other problems that may arise: confounding the extent antibiotics play a role when consideration other factors such as vaginal or cesarean birth (Bessi, et Al., 2010), underlying gastrointestinal disorders, chronic disease status, and functional or structural alterations. There may be other factors requiring further exploration. The goal with this type of inquiry is twofold: to reveal potential harm unnecessary use of antibiotics have on our health and to understand the importance healthy gut flora diversity contributes to our long-term health.

References

Dethlefsen, L., Huse, S., Relman, D., and Sogin, M. (2008). The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biology. 6(11): e280. Doi: 10.1371/journal.pbio.0060280

Bessi, E., Biasucci, G., Morelli, L., Retetangos, C., Riboni, S., and Rubini, M. (2010). Mode of delivery affects the bacterial community in the newborn gut. [Abstract].  Early Human Development. Jul(86), Suppl. 1:13-15. Retrieved February 10, 2012 from http://www.ncbi.nlm.nih.gov/pubmed/20133091

What are Cytokines?

Cytokines are proteins that signal cells to act throughout the body. They are inflammatory in nature and are classified as proteins, peptides, and polypeptides (a nice pictorial of cellular immunity at work). One commonly known cytokine, interferon type I is used to treat hepatitis B and C.


There is debate in the scientific community whether or not cytokines are hormones. This may be due in part to their anatomy, origin, and level of concentration in the body. Cytokines can be concentrated 1,000s times greater during trauma or infection. Hormones are generally secreted by localized organs/glands such as the pancreas while cytokines can be generated from nearly every nucleated cell in our body including macrophages (WBCs), endothelial cells (interior of our body) like those that line our blood vessels, and epithelial cells (surface of our body) like our skin.


Here is a video representation courtesy of nucleusinc.org:

Just thinking about the structure of cytokines brings to light the fact that they are all highly dependent upon adequate levels of cholesterol since cell membrane structural integrity and intracellular communication are all reliant on cholesterol. In addition, WBCs act immunoprotectively with cholesterol in the blood to bind to and inactivate toxins such as bacteria, viruses, fungi, and free radicals. Here is a good site with practical application tips to reduce inflammation while enhancing the body’s immunoprotective abilities naturally without dependence drugs which are partly responsible for iatrogenic disease and death. This also highlights one way cholesterol plays a role in immunity and how it may relate to other diseases such as cancer (McCully, Ravnskov & Rosch, 2011).  

Cytokines are active in both acute and chronic inflammation. This is a two edged sword since they actively facilitate immune responses in our body. Chronic inflammation can have detrimental long-term impact on our health and should be minimized since inflammation is a contributory factor in cardiovascular disease. This may be how statins are protective by reducing C-reactive protein (CRP) an inflammatory marker, needless to say the harm associated with statin’s cholesterol lowering effect is greater than its documented benefits.

There are many factors that stimulate chronic inflammation and this is the underlying issue we should seek to correct when considering any level of prevention. Addressing these health abnormalities through a symptomatic response (pharmaceuticals) can have untold long-term consequences including cancer.

The greatest benefit of acute inflammation occurs when we have an infection. Inflammation stimulates cholesterol production. The bad news is that as chronic inflammation continues it inhibits nitric oxide (NO), a potent vasodilator, increases blood pressure and places the lining of our blood vessels at increased risk through atherosclerosis. The mechanisms responsible for atherosclerosis are very complex and the presence of cholesterol does not necessarily indicate cause. One of statins’ benefits comes from inflammation reduction. According to Chris Masterjohn, (he describes the process in great detail here), statins can provide a co-occurring negative impact by reducing Coenzyme Q10 production which works in conjunction to NO to improve cardiovascular function and negate the effects of atherosclerosis. Statins are also known to cause muscle degeneration. Think about your heart. It is a muscle.


We need cytokines to keep us healthy when we get sick. We also need to understand how chronic inflammation occurs and to moderate the its effects by our lifestyle choices. When trying to mitigate these risks, understanding what causes inflammation and how to prevent it can reduce the risk of health problems down the road. We should approach it though our diet and lifestyle not a drug . . . unless you want to take that risk.


References

McCully, K., Ravnskov, U., and Rosch, P. (2011). The statin-low cholesterol-cancer conundrum. Quarterly Journal of Medicine. doi: 10.1093/qjmed/hcr243

Cholesterol, Immunity, and Infectious Disease

Cholesterol plays an important role in immunity, especially with bloodborne pathogens. One study here explained that total cholesterol (TC) fluctuates wildly during acute infections indicating cholesterol may have immune mediated activity. The article reviewed 19 cohort studies that revealed a correlation between increased death from respiratory and gastrointestinal diseases (both infectious) and low TC.

It also showed that people admitted to hospitals due to an infectious disease also had low cholesterol. Some common diseases noted were genitourinary infections, skin, and subcutaneous (just below the skin) infections. HIV and death from AIDS were also associated with lower cholesterol levels.

Patients with low TC suffering from chronic heart failure had a poorer prognosis after surgery and lower long-term survival rates. This also included patients recovering from abdominal surgeries. Another interesting note was that people suffering from hepatitis B including asymptomatic carriers also have lower TC levels.

Although the evidence shows that young and middle-aged men are at risk for heart disease with high cholesterol (this can be controlled through diet) their risk becomes negated when they get close to 50. As one gets older, higher cholesterol is associated with longevity 1, 2 in both men and women. This may be due to not only the cardioprotective effects of higher cholesterol but also to innate immunoprotective mechanisms associated higher TC.

Interestingly, eating a diet lower in fiber increases serum cholesterol due to the gut’s increased ability to reabsorb cholesterol in the absence of fiber. In addition to this, diets higher in linoleic and linolenic acids (essential fatty acids) may help prevent or reverse atherosclerosis (yes, atherosclerosis can be reversed).

Another article showed that one cause of cardiovascular disease may result from bacterial communities reinfecting arterial walls. Suppressed immune response related to low cholesterol may be a contributing factor.

If you want to reduce your risk of infection and improve immunity response mechanisms, one thing to consider is maintaining healthy cholesterol levels. Cholesterol may also play a role in a number of autoimmune disorders.