Past, Present, and Future of “Biological Aging” with Dr. Fitzgerald
The incidence of cardiometabolic disease is of great concern. According to the Center for Disease Control and the NIDDK 34.4% of us have metabolic syndrome, 39.8 percent of us are obese, obesity, 71.6 percent of us are overweight, 31 percent of us have fatty liver, in all age groups 9.4 percent of us have type 2 diabetes, and in adults, the rate is 12.2 percent, and 25 percent of deaths are from cardiovascular disease. Several years ago, I heard Lee M. Kaplan, MD, PhD, Director of Obesity, Metabolism, and Nutrition Institute at Mass General Hospital, speak at a probiotics conference. He said something that went deep into my psyche: “Gaining 20 pounds between the ages of 2 to 65 is the difference between 4-5 calories a day, or less than half a potato chip. No one has that much willpower.”1 Changes in diet and lifestyle offer only temporary solutions for most people, so what else could be driving metabolic disease? An important part of the solution lies in the gut.
This doesn’t seem obvious, because those of us who have cardiometabolic conditions often don’t have any obvious digestive concerns. Yet when we look at the drivers of dysbiosis (an unhealthy pattern of gut microbes) and the drivers of cardiometabolic disease, cancers, and other chronic health conditions, they share common origins: genetic predisposition, changes in our diet, lack of exercise and sleep, chronic stress, medications (especially antibiotics), toxins, hormone imbalances, endotoxemia, disruption of circadian rhythm, and whether we were bottle-fed or breastfed as infants.
As research on gut barrier function and gut microbes (aka the gut “microbiota”) expands, more is realized about the interconnectedness of the human body. One of the surprising areas is in the way that an unhealthy microbiota is a key driver of obesity, fatty liver disease, metabolic syndrome, type 2 diabetes, and cardiac risk. 2-4
A Taste of the Research
- Obesity and Dysbiosis: In obesity, dysbiosis leads to increased gut leakiness which drives inflammation and reduces insulin sensitivity.5 Numerous papers note the association between antibiotic exposure in utero, infancy, and early childhood and increased risk of obesity. 6-8
- Glycemic Response and the Microbiome: Researchers at the Weitzman Institute used continuous glucose monitoring in 800 people in Israel and in 2019 with 327 people from the midwestern United States with prediabetes and type 2 diabetes. They discovered that glycemic responses to specific foods are individual, something we have seen in practice for decades. Using machine learning that integrates lab values, diet, anthropometrics, exercise, and the gut microbiota, they were able to make personalized dietary recommendations that benefit glucose responses.9,10
- Circulating Microbial Products and Metabolic Disease: As part of the FINRISK study in 2452 people, it was found that increased levels of lipopolysaccharides (LPS) produced by harmful bacteria in the gut were consistently associated with obesity, metabolic syndrome, diabetes, and cardiovascular events. This was independent of risk factors including elevated CRP, total calorie or nutrient intake, or whether people were obese, had metabolic syndrome, or diabetes prior to the beginning of the study.
- Dysbiosis drives Fatty Liver Disease: Gut dysbiosis allows for the proliferation of microbes that are super-efficient at utilizing calories. This leads to weight gain, even if someone isn’t eating increased calories. The weight gain can lead to insulin resistance and ultimately non-alcoholic fatty liver disease.11
The Role of High-Fat, High-Glycemic Diets (aka modern, processed foods)
Dozens of papers strongly demonstrate that diets high in certain fats combined with high glycemic foods (those high in sugars and other refined carbohydrates) lead to increased intestinal permeability via increased lipopolysaccharides (LPS) from mainly gram-negative bacteria. A recent review of US food intake states that the average diet includes 70.9 percent of our total calories each day in ultra-processed foods that fit this high fat, high glycemic pattern.12 These contain fewer micronutrients, plant bioactives, and fiber and increase our intake of “acellular nutrients” such as flours, sugars, processed plant starches, in which the cellular structure of the food has been processed out. These omissions are likely also a big contributor to the negative effects. These stripped carbohydrates are rapidly metabolized, leading to stimulation of toll-like receptors (TLR) and increased LPS, leading to leaky barriers, inflammation, and immune activation.13 These diets also activate our immune system and activate inflammation; contribute to high blood glucose levels; and decrease beneficial short-chained fatty acids (SCFA). This increases dysbiosis which leads to obesity, metabolic syndrome, fatty liver, and type 2 diabetes. This is expressed in the diagram below.
A note about high-fat diet research: There is much confusion in the reporting of the effects of high-fat diets: both positive and negative effects are reported and it can be hard to know how to interpret them. Some things to know are that it seems to be the combination of high fat and high glycemic foods that is most problematic. In addition, fat quality makes a difference – as you’ll note in the diagram above, omega-3 fats have been shown to be beneficial (likely in the context of an otherwise omega-3 deficient diet), and we expect to be able to tease out more differences between different types of fats as more research becomes available. Lastly, high-fat diets in the form of supervised, short term ketogenic diets, when well-formulated with nutrient density, phytonutrients, and fiber, are not observed to have these same negative effects and are often able to re-establish cardiometabolic health.
Food Solutions: Whole Foods, Prebiotic-Rich Diet, and Fermented Foods
Dietary change promises the strongest solution to rebalance the microbiome. The microbial balance can change dramatically within 24 hours, yet in order to have more than a temporary shift we need to change our diets permanently.18-20 Shifting away from ultra-processed foods to a diet that comes from whole foods will create whole-body changes and changes to our microbiota and barriers.
Consuming more prebiotic-rich foods is part of the answer. Prebiotics are the food for the microbiota. These include foods that are rich in soluble fiber and resistant starch; polyunsaturated fatty acids from nuts and seeds; conjugated linoleic acid from grass-fed dairy products and meats, and fish; sea vegetables; polyphenols and other bioactive compounds in vegetables, fruits, nuts, seeds, legumes, and pulses; and all of our culinary spices and herbs. For maximum biome support, these foods ought to comprise at least 50% of what we put on our plates each day.
It’s the life in foods that gives us life. Adding cultured and fermented foods to our daily diet also gives us huge benefits. They reduce inflammation throughout the body, help to regulate bowel motility, increase B-complex vitamin and Vitamin K intake, improve mineral absorption, and have anti-microbial effects.21 Yogurt has been found to help with weight control, to reduce the risk of developing type 2 diabetes, and improves fasting insulin levels and serum lipids.22,23 Fermented milk reduced hemoglobin A1C and TNF-alpha levels.24 A teaspoon of raw, fresh honey contains 13 different species of Lactobacillus and Bifidobacterium at levels of 5 billion CFU. Add this to green or black tea and you now have a probiotic and prebiotic-rich beverage. While we don’t have research on each specific fermented food in relationship to cardiometabolic health, based on research in other areas we know them to reduce inflammation and be protective.
Take-Aways
If you, your patient, or a loved one is faced with some form of cardiometabolic disease, look to the gut for answers. Lifestyle alone will not get you sustained results in most cases without balancing the microbiota. Although exercise, sleep, our beliefs, and our relationships can have negative and positive effects on the microbiota, the fastest way to balance dysbiosis is through food. This happens within 24 hours but needs a permanent change in diet to sustain the benefits. The most important things that you can do is to eat a whole foods diet, focus on eating a lot more vegetables, fruits, nuts, seeds, and beans, to eat an adequate amount of plant and/or animal protein, and to include high-quality fats and oils. [See below for references].
If you are a clinician, patient, or someone serious about good health, this course is designed for you. You’ll learn how to uncover underlying root causes of digestive health problems and resolve chronic GI symptoms. You will discover how to deal with complex health issues and how to proceed when you don’t know what to do! In short, you’ll gain the keys to digestive wellness and living a happier, healthier life.
Register here.
- Kaplan LM. Obesity. Paper presented at: Diet and Microbiota in Health and Disease2015; Boston, MA.
- Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas M-EJGM. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. 2016;8(1):42.
- Dumas ME. Is the way we’re dieting wrong? Genome medicine. 2016;8(1):7.
- Devaraj S, Hemarajata P, Versalovic J. The human gut microbiome and body metabolism: implications for obesity and diabetes. Clinical chemistry. 2013;59(4):617-628.
- Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012;3(4):279-288.
- Mueller NT, Whyatt R, Hoepner L, et al. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. International journal of obesity (2005). 2015;39(4):665-670.
- Saari A, Virta LJ, Sankilampi U, Dunkel L, Saxen H. Antibiotic exposure in infancy and risk of being overweight in the first 24 months of life. Pediatrics. 2015;135(4):617-626.
- Schwartz BS, Pollak J, Bailey-Davis L, et al. Antibiotic use and childhood body mass index trajectory. International journal of obesity (2005). 2015.
- Mendes-Soares H, Raveh-Sadka T, Azulay S, et al. Model of personalized postprandial glycemic response to food developed for an Israeli cohort predicts responses in Midwestern American individuals. Am J Clin Nutr. 2019.
- Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-1094.
- Lau E, Carvalho D, Freitas P. Gut Microbiota: Association with NAFLD and Metabolic Disturbances. BioMed research international. 2015;2015:979515.
- Baldridge AS, Huffman MD, Taylor F, et al. The Healthfulness of the US Packaged Food and Beverage Supply: A Cross-Sectional Study. Nutrients. 2019;11(8).
- Spreadbury I. 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 Metab Syndr Obes. 2012;5.
- Candido FG, Valente FX, Grzeskowiak LM, Moreira APB, Rocha D, Alfenas RCG. Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity. Int J Food Sci Nutr. 2018;69(2):125-143.
- Lopez-Moreno J, Garcia-Carpintero S, Gomez-Delgado F, et al. Endotoxemia is modulated by quantity and quality of dietary fat in older adults. Experimental gerontology. 2018;109:119-125.
- Cremonini E, Wang Z, Bettaieb A, et al. (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance. Redox biology. 2018;14:588-599.
- Porras D, Nistal E, Martinez-Florez S, et al. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med. 2017;102:188-202.
- David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563.
- Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105-108.
- De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107.
- Sanlier N, Gokcen BB, Sezgin AC. Health benefits of fermented foods. Crit Rev Food Sci Nutr. 2019;59(3):506-527.
- Marco ML, Heeney D, Binda S, et al. Health benefits of fermented foods: microbiota and beyond. Curr Opin Biotechnol. 2017;44:94-102.
- Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus. Journal of dairy science. 2011;94(7):3288-3294.
- Tonucci LB, Olbrich Dos Santos KM, Licursi de Oliveira L, Rocha Ribeiro SM, Duarte Martino HS. Clinical application of probiotics in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled study. Clin Nutr. 2017;36(1):85-92.
2 Comments
Related posts
Great article. About adding raw honey to hot tea, would high temperature of tea kill honey probiotics ?
Honey doesn’t contain active probiotics, rather is a good sources of PREbiotic oligosaccharides, which can help promote healthy GI bacterial balance. Heat shouldn’t impact prebiotic benefit.