Nose temperature and rhinoviruses

NYT Rhinovirus

from NYT, click for original image and article

The Roman Celsus in the 1st century A.D. identified four classical signs of inflammation: Calor, dolor, rubor, and tumor; these are heat, pain, redness, and swelling. Some of the most annoying symptoms of a cold involve vascular congestion of mucous membranes, from increased blood flow leading to tissue swelling (tumor), increased warmth (calor), and mucus production. A new study suggests that of the inflammation hallmarks, calor may be critically important in defending us against viral infections, such as the common cold.

Carl Zimmer’s article in the New York Times today describes Akiko Iwasaki’s work on temperature and rhinovirus infection. The temperature of air in the nose may be a key risk factor for infection by rhinoviruses, the organism causing the common cold. The bottom line: cold temperature impairs cellular immunity and facilitates infection by the virus. Having gotten over one of these infections recently, I was very intrigued but not surprised by this work. The study’s author also hinted that fever is beneficial in preventing further infection by the virus. We have covered this hypothesis several times on this blog, e.g here and here. Ed LeGrand and I have written about the host defense function of elevated temperatures as a stressor that harms invaders more than ourselves.

My thought for today is: if cold air and tissues in the nose are an Achilles heel for us, allowing easy infection by rhinoviruses, does inflammation in the nose generate a localized fever that protects us?

A combination of a local defenses and body-wide defenses might be important in fighting infection. This view was proposed by Day and LeGrand in the Journal of Theoretical Biology. The study they published, Synergy of local, regional, and systemic non-specific stressors for host defense against pathogens suggests that combining local and systemic stresses like fever might be particularly valuable in preventing pathogen invasion. I will cover their new paper in more detail in the next post of this blog.

As a final thought, cold air induces rhinorrhea (runny nose) in many people even in the absence of infection. This vasomotor rhinorrhea involves tissue edema and increased blood flow. Maybe cold rhinorrhea prevents viral infections from getting established by expelling mucus and raising the temperature. If this is true, taking cold and allergy medications that prevent Celsus’s dolor, tumor, and calor might do more harm than good.

 

Elon Musk on Knowledge

Tree

On a Reddit Q&A, the space entrepreneur Elon Musk was asked,

“Do you have any advice on learning? How are you so good at it?”

His response:

“One bit of advice: it is important to view knowledge as sort of a semantic tree — make sure you understand the fundamental principles, ie the trunk and big branches, before you get into the leaves/details or there is nothing for them to hang on to.”

Evolution gives precisely this intellectual scaffolding.

As Mark Schwartz poetically wrote:

“teaching evolutionary concepts such as selection, common ancestry, phylogenetics, and tree-thinking provides an integrated, conceptual scaffold, a cognitive hat rack on which medical facts can be organized. Infusing the concepts of evolution into medical education can help students build the bridges and tunnels they need to connect and navigate what is otherwise an archipelago of basic and clinical sciences.” – excerpted from Alcock and Schwartz 2011 Evo Edu Outreach (2011) 4:574–579

 

High fat diet good or bad?

A study by Gower and Goss was just published in the journal Nutrition examining the role of dietary fat in insulin resistance:

RCT: A lower-carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes.

From the abstract:

(AA is African American, EA is European American; PCOS is Polycystic Ovary Disease)

participants who consumed the lower-carbohydrate vs. the lower-fat diet lost more intra-abdominal adipose tissue (IAAT) (11 ± 3% vs. 1 ± 3%; P < 0.05). After weight loss, participants who consumed the lower-carbohydrate diet had 4.4% less total fat mass. Original to this report, across the entire 16-wk study, AAs lost more fat mass with a lower-carbohydrate diet (6.2 vs. 2.9 kg; P < 0.01), whereas EAs showed no difference between diets. As previously reported, among women with PCOS, the lower-carbohydrate arm showed decreased fasting insulin (−2.8 μIU/mL; P < 0.001) and fasting glucose (−4.7 mg/dL; P < 0.01) and increased insulin sensitivity (1.06 arbitrary units; P < 0.05) and “dynamic” β-cell response (96.1 · 109; P < 0.001). In the lower-carbohydrate arm, women lost both IAAT (−4.8 cm2; P < 0.01) and intermuscular fat (−1.2 cm2; P < 0.01). In the lower-fat arm, women lost lean mass (−0.6 kg; P < 0.05). Original to this report, after the lower-carbohydrate arm, the change in IAAT was positively associated with the change in tumor necrosis factor α (P < 0.05).”

Does this mean that a high fat (e.g. Atkin’s) diet is preferable for weight loss and prevention of diabetes? At least for certain populations, such as AA and PCOS, this may be so.

Fat mass change

Lower carbohydrate intake resulted in lower intra-abdominal fat (the more dangerous visceral pattern of adiposity) in the eucaloric diet (A) and with hypocaloric (B) diets. These results suggest that a low carbohydrate diet might be more effective than low fat for short term weight loss. These results are intriguing in light of the wealth of molecular and animal model studies suggesting metabolic harm from a high fat diet. As we have pointed out in this blog, people are not mice, which may account for some of these differences. Previous epidemiological work implicated processed sugar and starch as important drivers of weight gain, but they also suggest that sources of fat, such as processed meats, also promote weight gain. As has been pointed out before, the kind of fat seems to play a role in outcomes such as cardiovascular disease. Given these uncertainties, it is too early to give a blanket recommendation for high fat diets. A long term study of low fat versus low carbs on weight gain and metabolism will be important to sort this out.

Meanwhile read this from the BMJ are some diets mass murder?

Which fats are good for you and your microbiota?

As a supplement to the recent post on fat and microbiota, I am posting a summary of what is known about various fats’ effects on the composition of gut microbiota and on intestinal barrier function.

Short Chain Fatty Acids Protect Against Obesity

From Kimura et al. 2014 Gut microbiota protect against obesity via short chain fatty acid receptors

High fat diet causes dysbiosis and impaired intestinal barrier function

Cani et al 2007 Metabolic Endotoxemia Initiates Obesity and Insulin Resistance

Pederson 2013 high-fat diet increases Streptococcaceae, Enterobacteriaceae and E. coli

Jakobsdottir 2014 High fat diet reduces SCFA reversible with fiber

Ma 2014 High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model - high fat diet reduces commensal Campylobacter

Huang 2013 Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue- n-6 PUFA, LARD and Milk Fat change microbiota and induce insulin resistance.

Zhang 2010 Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. Decreased Bifidobacteria.

de la Serre 2010 Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation.

Deopurkar 2010 Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin. Saturated fat causes endotoxemia

Kim 2012 High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway – increased Enterobacteriaceae and endotoxemia

Carvalho 2012 High fat diet dysbiosis and impairment of insulin sensitivity prevented with antibiotics

Le Roy Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Microbiota are the causal feature controlling the inflammatory response to high fat diet.

Ridaura 2013 Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice - high saturated fat diet prevented phenotypic rescue of obese mice during co-housing of lean and obese mice.

Brown 2012 Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease. Excellent review

Saturated fats cause dysbiosis

Devkota et al. FASEB

Devkota et al. 2012 Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10−/− mice. saturated fat increased δ-Proteobacteria Bilophila wadsworthia.

Shen et al. Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes

Kim 2012 High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway

Mani 2013 Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia – saturated FA increased endotoxemia

Oleic acid (monounsaturated fat) prevents HFD dysbiosis and increases Bifidobacteria

Omega-3 fatty acids prevent dysbiosis and promote beneficial microbes

Myles et al. Effects of Parental Omega-3 Fatty Acid Intake on Offspring Microbiome and Immunity

Mujico 2012 changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice

Muller 2014 FASEB

Ghosh 2013 Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid- Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

Ghosh 2013 Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice.

Mani 2013 Dietary oil composition differentially modulates intestinal endotoxin transport and postprandial endotoxemia – omega-3 FA decreased endotoxemia

Patterson 2013 Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice – omega-3 FA increased Bifidobacteria.

Omega-6 fatty acids cause dysbiosis

Ghosh 2013 Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid- Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

Ghosh 2013 Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice.

Zeng 2013 Fatty Liver Accompanies an Increase in Lactobacillus Species in the Hind Gut of C57BL/6 Mice Fed a High-Fat Diet – n-6 fat caused expansion of bile salt resistant bacteria associated with fatty liver.

Hildebrandt 2009 High-fat diet determines the composition of the murine gut microbiome independently of obesity. n-6 safflower oil increased Proteobacteria

Prebiotics increase protect against dysbiosis and increase Bifidobacteria and improve metabolism

Everard ISME J. 2014 Microbiome of prebiotic-treated mice reveals novel targets involved in host response during obesity

Cani 2007 Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes

Short chain fatty acids

Jakobsdottir 2014 High fat diet reduces SCFA reversible with fiber

Bottom line:  Avoid excess saturated fats (and n-6 PUFA). For metabolic health, consume omega-3 fatty acids, olive oil, and prebiotics that promote short chain fatty acids.