Blood-pressure lowering mouth microbes killed by mouthwash

A building body of work indicates that the oral microbiota is intimately connected with human cardiovascular physiology. It was already known that poor oral health, especially gingivitis, is linked with atherosclerosis and heart attacks. A report the journal Free Radical Biology and Medicine suggests that too much oral hygiene might also be bad for cardiovascular health. In this study, Kapil and colleagues provided intriguing evidence that oral nitrate-reducing microbiota influence blood pressure control in humans. When these microbes were eliminated with antiseptic mouthwash, blood pressure measurably increased! This significant result was seen in a relatively small cohort, suggesting a potentially robust effect (one that will need to be confirmed with follow up research).

From the abstract:

“We measured blood pressure (clinic, home, and 24-h ambulatory) in 19 healthy volunteers during an initial 7-day control period followed by a 7-day treatment period with a chlorhexidine-based antiseptic mouthwash. Oral nitrate-reducing capacity and nitrite levels were measured after each study period. Antiseptic mouthwash treatment reduced oral nitrite production by 90% (p < 0.001) and plasma nitrite levels by 25% (p = 0.001) compared to the control period. Systolic and diastolic blood pressure increased by 2–3 .5 mm Hg, increases correlated to a decrease in circulating nitrite concentrations (r2 = 0.56, p = 0.002). The blood pressure effect appeared within 1 day of disruption of the oral microflora and was sustained during the 7-day mouthwash intervention. These results suggest that the recycling of endogenous nitrate by oral bacteria plays an important role in determination of plasma nitrite levels and thereby in the physiological control of blood pressure.”

Even though I knew that obliterating the microbiota in other body locations, like the gut, is harmful, I have been conditioned by dentists and marketers to think that a healthy mouth is one with few bacteria. Not so, apparently! It makes me wonder about other unintended consequences of commonly used antiseptics like chlorhexidine – for instance its use in hand soaps in the hospital. Perhaps we will find that those antibacterial products also can disrupt healthy microbial communities and harm human health.

Read the full text open access article here:

Physiological role for nitrate reducing oral bacteria in blood pressure control. Free radical biology and medicine

Malaria parasites remodel the odor of blood to attract mosquitoes

Volatile compounds produced by falciparum

In a cool new finding, Kelly and colleagues recently reported that malaria parasites, Plasmodium falciparum, produce volatile compounds in blood that are attractive to mosquitoes. These sweet smelling volatiles are similar to terpenes produced by plants. The evolutionary origin of these compounds is intriguing to consider. Are they attractive to mosquitoes because of their similarity to plant compounds that provide a source of food for Anopheles and other mosquitoes. (In fact, male Anopheles mosquitoes feed exclusively on plant and nectar). Do parasites hijack the sensory apparatus of mosquitoes with these redolent products? Or, do mosquitoes find these smells attractive because they are less likely to be swatted by a malaria infected host? Time, and additional experimentation, will tell.

Read the open access paper in mBio here:

Kelly M. et al. Malaria Parasites Produce Volatile Mosquito Attractants. mBio vol. 6 no. 2 e00235-15

Also: Mosquitoes are more likely to seek out human blood after infection with Plasmodium. Another example of hijacking of host neural machinery? Or something more mutually beneficial?

Antibiotics harm our earliest symbionts – mitochondria

Mitochondria

Mitochondrion

 

Researchers have discovered more unintended consequences for antibiotics, this time for our earliest endosymbionts, the mitochondria.

Commonly-used antibiotics in the tetracycline class have been shown to impair cellular respiration and mitochondrial function in eukaryotic cells, from plants to mice to fruit flies, and in human cell cultures. Tetracyclines have been known to impair mitochondrial translation for decades, but the recent work shows that the effect is powerful and pervasive.  From The Scientist:  “researchers have now shown that even low concentrations of tetracyclines can inhibit mitochondrial function and lead to changes in both mitochondrial and nuclear protein expression. ”

From the paper by Moullan et al.:

“… the complete microbiome is estimated to be ten times larger than the number of cells in a human body (1014 bacteria versus 1013 cells), possibly explaining why early life exposure to antibiotics severely impacts metabolic traits through disruption of microbial homeostasis…One should keep in mind, however, that tetracyclines and some other antibiotic classes also inhibit the mitochondria—to be considered as bacteria within our cells—the population of which approximately exceeds the number of bacterial cells by a further order of magnitude (1015 mitochondria), thus providing a strong platform for adverse effects.”

Read more about this thought-provoking result in The Scientist here.

Reference with full text open-access (highly recommended):

Moullan et al., “Tetracyclines disturb mitochondrial function across eukaryotic models: a call for caution in biomedical research,” Cell Reports, doi:10.1016/j.celrep.2015.02.034, 2015.

How doctors think: bias towards action

In 2001, a paper by van den Berghe and colleagues was published in the New England Journal of Medicine. It described a trial of intensive blood sugar control in critically ill patients and reported improved survival with intensive glucose treatment using insulin.

This study led to a substantial increase in aggressive hyperglycemia treatment known as “tight glycemic control” in the intensive care unit.

In 2009, another paper refuted the results of the first. The NICE SUGAR study enrolled 6000 critically ill patients, randomizing 3000 of them to tight glycemic control. The key result:

  • mortality was higher (27.5% v. 24.9%) in the intensive insulin treatment arm

After this widely cited study, guess what happened to patients with hyperglycemia. Was tight glycemic control abandoned? Amazingly, No!

A recent study in JAMA reported that tight glycemic control continued without significant change after NICE SUGAR. Fewer dangerous hypoglycemia events occurred, but efforts to normalize high blood sugar continued as if the NICE SUGAR study never happened. Is it unethical to continue therapies that have been demonstrated to cause harm? Yes. Why does it happen?

This result betrays the bias towards action among physicians. Many of us have a hard time doing nothing, even when that is the most appropriate course of action.

The JAMA paper argues for de-adoption of useless therapies, like tight glycemic control. It is likely that evolutionary medicine can help promote de-adoption of harmful interventions by re-defining what is abnormal and should be treated versus what is normal and should be left alone.

See also: http://evolutionmedicine.com/2014/06/02/harm-when-physicians-treat-normal-as-abnormal/

and: http://evolutionmedicine.com/2014/09/03/when-to-treat-when-to-leave-alone/

References:

van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367.

Finfer S, Chittock DR, Su SY, et al; NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.

Niven D, Rubenfeld G, Kramer A, Stelfox H. Effect of Published Scientific Evidence on Glycemic Control in Adult Intensive Care Units. JAMA Intern Med. 2015 Mar 16. doi: 10.1001/jamainternmed.2015.0157.

 

Multi-organ failure in sepsis: good or bad?

Mervyn Singer has published a review of multiple organ failure in patients with septic shock. Singer proposes that organ failure may represent a kind of organ hibernation that helps promote survival.

He writes:

“In summary, there is significant evidence that implicates mitochondrial dysfunction in sepsis-induced organ dysfunction. Whether this is causative or epiphenomenal is less clear. However, survivors have better preservation of ATP, mitochondrial function, and biogenesis markers. Multi-organ failure may however represent a mechanism through which the likelihood of eventual survival is enhanced in those hardy enough to survive as cells may enter a “hibernating” state in the face of overwhelming inflammation.”

This view is a departure from the traditional view of organ failure as maladaptive harbinger of death.

Read the entire paper here.