Re: Role of the gut microbiota in nutrition and health
Several more factors have the potential to influence how diet affects health through the microbiota
Valdes et al. write that the microbiota should be considered a key aspect in nutrition. We would argue that this is an understatement - or perhaps even a misrepresentation of how diet relates to the microbiota. The totality of the evidence points to the microbiota not being an aspect in nutrition science, but the very mediator of many of the negative effects of the Western/modern diet.
A clear example of this are microbiota transplants in rodents, in which test-animals are exposed to different kinds of diet treatments. The phenotype caused by the treatments can then be transferred to other non-exposed individuals, solely by transferring the microbiota ( 1-3). In other words, the recipe for the disease or malfunction induced by the diet is stored within the microbiota.
The microbiota can also be a source of error in diet studies if the microbiota is not standardized/analyzed, and could lead to apparently conflicting results by different researchers studying the same hypothesis. This means that a large part of diet studies conducted before “the era of the metagenome” should be looked at anew. Still today, studies far from always control for microbiota differences across cohorts or individuals, or discuss if the results could have been influenced by the microbiota (4-6).
Valdes et al. point to a few single diet factors that have been shown to affect the microbiota negatively, and a few areas that are in the category “we don’t know”. Perhaps not intended, Valdes et al. appear to approach how diet can affect the microbiota solely by looking at single diet characteristics in isolation. Given the fact that a Western diet has been shown to consistently yield negative health effects in rodents (7), and the fact that no single diet factors such as emulsifiers, sweeteners, pesticides or saturated fat content have been either widely acknowledged as a cause or as having a clear mechanism for giving adverse effects in humans, there is a need to both look at a Western diet both as a whole, and to look for unrecognized diet factors, in order to come closer to how diet so profoundly can affect health. In that respect a factor that has changed to a large degree recently, is the immediate nutrient accessibility in food products. As compared to pre-civilization times the content of acellular nutrients in human diets has increased dramatically (8), potentially flooding the human microbiota with easily accessible nutrients. The significance of this has not been tested directly in human studies. However, increased nutrient accessibility has been shown to induce virulence factors in bacteria (9), and in a human study it was found that the larger the amount of rice (a cellular food) that was eaten relative to the amount of flour based foods (acellular foods) the more favorable was the effect on leptin levels (10).
Not only can food structure changes affect the microbiota in the body, but they can also lead to microbe induced changes in foods that occur after processing and before the food is eaten. Some processed foods will generally have an increase in the level of PAMPS (pathogen associated molecular patterns), compared to foods prepared from fresh, whole foods. In a study a diet with a reduced content of PAMPS was found to reduce cardiovascular risk factors (11).
When approaching how diet affects lifestyle diseases through the microbiota, we argue that there is a stronger need than pre-metagenome-times to investigate diet factors not solely as single factors, but as foods and meals as they are usually eaten, that is, having several different probable negative (and positive) characteristics at the same time. This is in part because more than 99 % of the genes in the human body (i.e. the microbiota) has the potential to be changed, whereas the human genes in an individual cannot (solely their expression). This renders the microbiome, in theory, more susceptible to permanent changes, and “multiple hits” (by for instance a diet consisting of heavily processed foods) are more likely to effect such changes. One way of studying multiple, simultaneous hits is to classify foods according to the degree of processing, thus encompassing several attributes at the same time. Studying how the degree of processing is associated with health outcomes has been shown to be meaningful in several studies (12-14). We believe however, that the classifications used to date may have been too coarse, or have not included sufficient aspects related to food structure or other characteristics, as discussed in our recent review (15 ). Future studies should aim at better elucidating how different kinds of processing change the chemical and physical properties of foods, and in turn how that affects the microbiota, to better allow for making classifications that are linked to actual biological effects.
1. Christine A. Olson et al., “The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet,” Cell 173, no. 7 (June 14, 2018): 1728-1741.e13, https://doi.org/10.1016/j.cell.2018.04.027.
2. Chao Kang et al., “Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet,” MBio 8, no. 3 (23 2017), https://doi.org/10.1128/mBio.00470-17.
3. Peter J. Turnbaugh et al., “The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice,” Science Translational Medicine 1, no. 6 (November 11, 2009): 6ra14, https://doi.org/10.1126/scitranslmed.3000322.
4. Karin Ried et al., “Does Chocolate Reduce Blood Pressure? A Meta-Analysis,” BMC Medicine 8 (June 28, 2010): 39, https://doi.org/10.1186/1741-7015-8-39.
5. Márcia Regina Simas Gonçalves Torres and Antonio Felipe Sanjuliani, “Does Calcium Intake Affect Cardiovascular Risk Factors and/or Events?,” Clinics (Sao Paulo, Brazil) 67, no. 7 (July 2012): 839–44.
6. Mette Svendsen et al., “The Effect of Kiwifruit Consumption on Blood Pressure in Subjects with Moderately Elevated Blood Pressure: A Randomized, Controlled Study,” Blood Pressure 24, no. 1 (February 2015): 48–54, https://doi.org/10.3109/08037051.2014.976979.
7. Turnbaugh et al., “The Effect of Diet on the Human Gut Microbiome.”
8. Ian Spreadbury, “Comparison with Ancestral Diets Suggests Dense Acellular Carbohydrates Promote an Inflammatory Microbiota, and May Be the Primary Dietary Cause of Leptin Resistance and Obesity,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 5 (July 6, 2012): 175–89, https://doi.org/10.2147/DMSO.S33473.
9. Reetta Penttinen et al., “High Nutrient Concentration Can Induce Virulence Factor Expression and Cause Higher Virulence in an Environmentally Transmitted Pathogen,” Microbial Ecology 72, no. 4 (November 2016): 955–64, https://doi.org/10.1007/s00248-016-0781-1.
10. Tommy Jönsson et al., “A Paleolithic Diet Is More Satiating per Calorie than a Mediterranean-like Diet in Individuals with Ischemic Heart Disease,” Nutrition & Metabolism 7 (November 30, 2010): 85, https://doi.org/10.1186/1743-7075-7-85.
11. M. Herieka, T. A. Faraj, and C. Erridge, “Reduced Dietary Intake of Pro-Inflammatory Toll-like Receptor Stimulants Favourably Modifies Markers of Cardiometabolic Risk in Healthy Men,” Nutrition, Metabolism, and Cardiovascular Diseases: NMCD 26, no. 3 (March 2016): 194–200, https://doi.org/10.1016/j.numecd.2015.12.001.
12. Diana Barbosa Cunha et al., “Ultra-Processed Food Consumption and Adiposity Trajectories in a Brazilian Cohort of Adolescents: ELANA Study,” Nutrition & Diabetes 8, no. 1 (May 25, 2018): 28, https://doi.org/10.1038/s41387-018-0043-z.
13. B. Melo et al., “Associations of Ultra-Processed Food and Drink Products with Asthma and Wheezing among Brazilian Adolescents,” Pediatric Allergy and Immunology: Official Publication of the European Society of Pediatric Allergy and Immunology, April 21, 2018, https://doi.org/10.1111/pai.12911.
14. Thibault Fiolet et al., “Consumption of Ultra-Processed Foods and Cancer Risk: Results from NutriNet-Santé Prospective Cohort,” BMJ (Clinical Research Ed.) 360 (14 2018): k322.
15. Marit K. Zinöcker and Inge A. Lindseth, “The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease,” Nutrients 10, no. 3 (March 17, 2018): 365, https://doi.org/10.3390/nu10030365.
Competing interests: No competing interests