Diverse Microbiome

Optimal Microbiome: Diverse Microbiome

Slide 1: DIVERSE MICROBIOME

Ecology 101 states that biodiversity is a predictor of health for most ecosystems. The human and mammalian microbiome is no exception. While there are many controversies and confounding variables left to interpretation from research on the microbiome, meta-analysis and review studies indicate that a diverse microbiome is a consistent predictor of health within a species and that a lack of microbial diversity (LOMD) is indicative of dysbiosis and correlate with an epidemic of chronic Western disease.

Basics on the microbiome:

https://www.facebook.com/PawsitivelyPrimal/videos/1634890073272457/

Bäckhed, F., Fraser, C. M., Ringel, Y., Sanders, M. E., Sartor, R. B., Sherman, P. M., ... & Finlay, B. B. (2012). Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell host & microbe, 12(5), 611-622.

Larsen, O. F., & Claassen, E. (2018). The mechanistic link between health and gut microbiota diversity. Scientific reports, 8(1), 2183.

Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight,

R. (2012). Diversity, stability and resilience of the human gut microbiota. Nature, 489(7415), 220.

Deng, P., & Swanson, K. S. (2015). Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. British

Journal of Nutrition, 113(S1), S6-S17.

Handl, S., Dowd, S. E., Garcia-Mazcorro, J. F., Steiner, J. M., &

Suchodolski, J. S. (2011). Massive parallel 16S rRNA gene pyrosequencing reveals highly diverse fecal bacterial and fungal communities in healthy dogs and cats. FEMS microbiology ecology, 76(2), 301-310.

Slide 2 CHARACTERISTICS OF DIVERSE MICROBIOME

For a diverse microbiome to function optimally, it requires keystone strains that perform essential functions. Without these keystone strains, we may not have a resistant and resilient microbiome. Diverse microbiome with keystone strains can withstand environmental assaults with less change to their composition than a LOMD and faster return to homeostasis after a disruption to the microbiome. A diverse microbiome is resistant to perturbations in the environment and resilient in that they quickly return to their previous state after a disturbance.

Diversity explained:

https://www.facebook.com/PawsitivelyPrimal/videos/304273450174352/

Shade, A., Peter, H., Allison, S. D., Baho, D., Berga, M., Bürgmann, H., & Matulich, K. L. (2012). Fundamentals of microbial community resistance and resilience. Frontiers in microbiology, 3, 417.

Cao, Y., Shen, J., & Ran, Z. H. (2014). Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterology research and practice, 2014.

Velasquez-Manoff, M. (2015). Gut microbiome: the peacekeepers. Nature, 518(7540), S3-S11.

Slide 3 Keystone Strains

In the microbiome, keystone strains have an extraordinary impact on an ecosystem relative to its population. Keystone strains are critical for the general structure and function of an ecosystem, and influence which other types of bacteria, fungus, virus, and parasites make up that ecosystem. A famous example of keystone species in conservation biology is the predator-prey relationship through the re-introduction of the wolf into Yellowstone Park. Predators that consume herbivorous species prevent herbivores from decimating the plant species in an ecosystem, which in turn removes shelter and food for countless smaller species. Without the keystone species (wolf), the herbivore population would continue to grow and consume all the dominant plant species in the ecosystem.

In humans, dogs, and other mammals, there are keystone microbes that are essential for function and maintenance of the microbiome. Without these keystone species, pathogenic microbes may flourish, and systems fail.

Wagner, S. C. (2010) Keystone Species. Nature Education Knowledge 3(10):51

Cani, P. D., & de Vos, W. M. (2017). Next-generation beneficial microbes: the case of Akkermansia muciniphila. Frontiers in microbiology, 8, 1765.

Maria, A. P. J., Ayane, L., Putarov, T. C., Loureiro, B. A., Neto, B. P., Casagrande, M. F., ... & Carciofi, A. C. (2017). The effect of age and carbohydrate and protein sources on digestibility, fecal microbiota, fermentation products, fecal IgA, and immunological blood parameters in dogs. Journal of animal science, 95(6), 2452-2466.

Velasquez-Manoff, M. (2015). Gut microbiome: the peacekeepers. Nature, 518(7540), S3-S11.

Citi, S. (2018). Intestinal barriers protect against disease. Science, 359(6380), 1097-1098.

Slide 4 RESISTANT

A resistant microbiome will experience less change in diversity when exposed to perturbations or stress. For example, a dose of antibiotics given to an organism with a diverse microbiome will have less impact on the ecosystem than a dose of antibiotics given to a body with a LOMD.

An example is a plant monoculture exposed to a pathogenic bacteria versus a rainforest exposed to the same pathogen. The rainforest, with its diverse organisms, many of which are redundant in function, is less susceptible to change in the environment from pathogens. Should one plant be decimated, there are many other plants with similar capacities that will replace it and maintain the organisms dependent on that plant species.

Biodiversity in an ecosystem:

https://www.facebook.com/PawsitivelyPrimal/videos/304273450174352/

Shade, A., Peter, H., Allison, S. D., Baho, D. L., Berga, M., Bürgmann, H., & Matulich, K. L. (2012). Fundamentals of microbial community resistance and resilience. Front Microbiol 3: 417.

Slide 5 RESILIENT

Resilience is how fast the microbiome bounces back from perturbations. An example is the Hadza of Tanzania, a hunter-gather tribe that has been extensively studied for their lack of western disease and natural way of living. These people’s microbiome has double the diversity of western populations. They can take a course of antibiotics, and the diversity of species can return within days. Whereas a western person, with a LOMD, may not reestablish their baseline diversity for months and in some cases, experience extinction of many species.

Again, in the fact of a monoculture, say where a particular species of grass is growing on a grassland, a perturbation, such as a drought, could decimate the landscape and destroy the organisms dependent on that grass. However, in grassland where 20 different kinds of grass share this ecosystem, drought-resistant grasses may live through the drought and replenish the landscape quickly so that the organisms, herbivores, insects, small mammals, and so on, in that ecosystem may continue to live. The speed of recovery if faster in a diverse ecosystem.

Biodiversity in an ecosystem: https://www.facebook.com/PawsitivelyPrimal/videos/304273450174352/

Shade, A., Peter, H., Allison, S. D., Baho, D. L., Berga, M., Bürgmann, H., & Matulich, K. L. (2012). Fundamentals of microbial community resistance and resilience. Front Microbiol 3: 417.

Slide 6 TWO WAYS TO INCREASE DIVERSITY

Several factors affect the diversity of the microbiome; some are set, such as age, birthing method, genetics, and others are malleable, such as physical activity, antibiotic exposure, diet, and environmental exposure. Most adjustable factors, such as diet, has been extensively studied and quantified. The Regional Species Pool (RSP), macro and micro exposure, is less analyzed due to the variability in environments and difficulty in controlling and measuring these variables. However, research shows that the availability of microbiota members mitigate extinction events, demonstrating how species reintroduction and repopulation may occur through contact with a natural environment.

Fragiadakis, G. K., Smits, S. A., Sonnenburg, E. D., Van Treuren, W., Reid, G., Knight, R., ... & Sonnenburg, J. L. (2018). Links between environment, diet, and the hunter-gatherer microbiome. bioRxiv, 319673.

Tropini, C., Moss, E. L., Merrill, B. D., Ng, K. M., Higginbottom, S. K., Casavant, E. P., ... & Bhatt, A. S. (2018). Transient Osmotic Perturbation Causes Long-Term Alteration to the Gut Microbiota. Cell, 173(7), 1742-1754.

SLIDE 7 DIET

It has been well-established that a diet is effectively used to alter the microbiome. In human studies, indigenous hunter-gather cultures are virtually free of Western disease such as diabetes, obesity, autoimmunity, Alzheimer's, etc., despite various diets, all these people have one thing in common: a diverse microbiome. Studies show that the average American eats 10 – 15 foods a year (think potatoes, broccoli, steak, eggs, spinach) while the average American gardener eats about 30 foods a year. The long-lived, disease free people of blue zones (areas with a higher rate of centenarians) eat significantly more foods per year than Westerners and the indigenous hunter-gather tribe, the Hadza, eat up to 600 different foods a year. Similar results have shown in wild canids and dog comparisons, where species richness of the microbiome was higher in animals eating a diverse fresh food diet over a processed kibble.

1. Variety of fresh food: It is consistently shown that consumption of a variety of fresh foods can increase the diversity of the microbiome. Certain foods have a more significant impact on diversity. For example, different types of fiber and resistant starch are shown to have a more substantial effect on keystone strains and production of short chain fatty acids (SCFA), a beneficial metabolite.

2. Sourcing includes the nutrient and composition of the soil in which the food was grown or animals graze. Also, the use of pesticides, such as glyphosate, which does not affect mammalian cells but destroys beneficial bacteria and creates an environment for pathogenic bacteria, such as E.coli to grow in the microbiome. It also includes irradiation, high-pressure pasteurization (HPP), pasteurization and other pathogen management techniques that remove beneficial bacteria from soil or foods. Subclinical antibiotics in farming animals also have a tremendous impact on the microbiome when consumed.

3. Timing IF/CRON: Intermittent fasting and calorie reduced optimal nutrition. It has been well established for more than 50 years that reduced calorie consumption can increase the life of most invertebrate, insects, and small mammals, including dogs. Recently, there has been more research into the use of time-restricted feeding to elicit the benefits of CRON without being in a constant state of semi-starvation and without the tedious precision of measuring nutrient-dense foods to prevent nutritional deficiencies. What may appear counterintuitive, intermittent fasting can increase the diversity of the microbiome and reestablish an environment for beneficial bacteria to flourish.

Diet excerpt:

https://www.facebook.com/PawsitivelyPrimal/videos/257359501642527/

Ackerman, N. (2017). The canine microbiome. The Veterinary Nurse, 8(1), 12-16.

Finlayson-Trick, E. C., Getz, L. J., Slaine, P. D., Thornbury, M., Lamoureux, E., Cook, J., ... & Cheng, Z. (2017). Taxonomic differences of gut microbiomes drive cellulolytic enzymatic potential within hind-gut fermenting mammals. PloS one, 12(12), e0189404.

Sandri, M., Dal Monego, S., Conte, G., Sgorlon, S., & Stefanon, B. (2016). Raw meat-based diet influences faecal microbiome and end products of fermentation in healthy dogs. BMC veterinary research, 13(1), 65.

Heiman, M. L., & Greenway, F. L. (2016). A healthy gastrointestinal microbiome is dependent on dietary diversity. Molecular metabolism, 5(5), 317-320.

De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., ... & Lionetti, P. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.

Proceedings of the National Academy of Sciences, 107(33), 14691-14696.

Handl, S., Dowd, S. E., Garcia-Mazcorro, J. F., Steiner, J. M., &

Suchodolski, J. S. (2011). Companion animals symposium: microbes and gastrointestinal health of dogs and cats. Journal of animal science, 89(5), 1520-1530.

Remely, M., Hippe, B., Geretschlaeger, I., Stegmayer, S., Hoefinger, I., & Haslberger, A. (2015). Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: a pilot study. Wiener klinische Wochenschrift, 127(9-10), 394-398.

Parker, J. (2015). A new hypothesis for the mechanism of glyphosate induced intestinal permeability in the pathogenesis of polycystic ovary syndrome. Journal of the Australasian College of Nutritional and Environmental Medicine, 34(2), 3.

Dao, M., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Verger, E., Rizkalla, S., ... & Clément, K. (2015). Akkermansia Muciniphila and Gut Microbiota Richness are Associated with Improved Metabolic Status after Calorie Restriction. The FASEB Journal, 29(1_supplement), 601-3.

Graef, F. A., Lau, J., Bosman, E. S., Kuan, M., Yang, H., Celiberto, L. S., ... & Surette, M. (2018). A8 PROLONGED FASTING ALTERS THE GUT

MICROBIOME AND PROTECTS AGAINST SALMONELLA-INDUCED GUT INFLAMMATION. Journal of the Canadian Association of Gastroenterology, 1(suppl_1), 14-15.

SLIDE 8 REGIONAL SPECIES POOL

The regional species pool (RSP) consists of all of the plants, animals, invertebrates, water, and soil in a designated area. When there is much diversity in species on the macro scale, then, in turn, there is extraordinary diversity in microorganisms.

In Western cultures, diet drives and modulates the microbiome. However, in hunter-gatherer communities, like the Hadza of Tanzania, diet can vary significantly between individuals in the tribe, most notably through the sexual division of labor, where women eat more vegetables, fruit, and tubers and men eat more hunted meats. Yet despite the variety in macros, their microbiome remains similar. Here the explanation is the constant exposure to the diverse organisms in the environment, from large animals to the microorganisms on the animals, to the microorganisms in the soil and the water can overcome the differences we typically see in Western diets that vary on the macro scale (Keto, vegetarian, paleo, etc).

1. Vegetation: “Forest Bathing” where people walk in forests has been scientifically studied in Japan since the 1980s with quantitative data on biomarkers indicating exposure to natural environments are beneficial to humans and animals. Another example is a study in Finland that found people who lived in an area with access to 30 or more native plants had less incidence of allergies that those who were exposed to urban microbes.

2. Animals: There is extensive data on what is termed “The Farm Effect,” where children exposed to farming animals are significantly less likely to develop allergies. These people consistently have a more diverse microbiome. Moreover, the amount of endotoxins in a mother's bed is predictive of the change of her children having allergies (the more endotoxins, the less likely to be allergic). We also know that families with dogs have more diverse microbiome and their children are less likely to have allergies. The same effect is not found with cats, likely because they are typically confined to indoors and do not have the opportunity to bring the outdoor microbes into the home.

3. Soil and water: The first written account of human geophagy, the eating of dirt, comes from Hippocrates more than 2,000 years ago. We see mammals, including dogs eating dirt. Consuming dirt protects the stomach against toxins, parasites, and pathogens. There is much more research on the benefits of dirt on humans and mammals including regulating mood, increasing diversity, maintaining the gut lining.

There are nonparasitic mycobacteria teaming in untreated water and soil which humans and animals have imbibed in regularly prior to industrialization that filtered our water and sanitized our foods and homes. It is proposed through the “Hygiene Hypothesis” that these bacteria, some called saprophytes, are integral in training the mammalian immune system.

Dr Graham Rook from the University College London suggests that the constant exposure to the pseducommensal bacteria such as saprophytes create a state where “coevolution leads to codependence.” He illustrates this concept with Vitamin C. Most mammals make their own vitamin C, like dogs do. However, in the evolutionary past, primates outsourced this production to plants. An ability to gorge on fruits made this gene redundant. He suggests mammals have outsourced immune regulation to many bacteria and we are now faced with allergies and chronic disease because we have removed a redundant regulator. This phenomenon can explain the health benefits experienced when exposed to natural water and soil sources.

However, much of the RSP research has come out of the work with the indigenous hunter-gatherer people, the Hadza of Tanzania, and similar areas such as noted in Europe and the Americas with "The Farm Effect" and "forest bathing" observed in Japan. These studies support the exposure to natural environments in quantifiably increasing beneficial impact from commensal microbes. Other researchers have shown that ‘filthy' environments (think factory farms and chemical laden inner-city boroughs) have shown to have a negative impact on the microbiome. This is also why some scientists are asking for a replacement for the term "Hygiene Hypothesis" in describing this phenomenon. While researches do not know the exact makeup of the microbial ecosystem that benefits humans and animals, they have shown that prenatal and first-year life exposure to natural and diverse microbes decrease the likelihood of developing allergies and chronic Western disease.

One aspect of RSP:

https://www.facebook.com/PawsitivelyPrimal/videos/1450497265045073/

Adair, K. L., & Douglas, A. E. (2017). Making a microbiome: the many determinants of host-associated microbial community composition. Current opinion in microbiology, 35, 23-29.

Hanski, I., von Hertzen, L., Fyhrquist, N., Koskinen, K., Torppa, K., Laatikainen, T., ... & Vartiainen, E. (2012). Environmental biodiversity, human microbiota, and allergy are interrelated. Proceedings of the National Academy of Sciences, 109(21), 8334-8339.

Wlasiuk, G., & Vercelli, D. (2012). The farm effect, or: when what and how a farming environment protects from asthma and allergic disease. Current opinion in allergy and clinical immunology, 12(5), 461-466.

Mazur, A., Szylling, A., Bielecka, T., Strzelak, A., & Kulus, M. (2017). Is the “farm effect” hypothesis still current? Atopy and allergic diseases in rural and urban children in Poland. Journal of Asthma, 1-9.

Forest Bathing: https://www.youtube.com/watch?v=9jPNll1Ccn0

Flies, E. J., Skelly, C., Negi, S. S., Prabhakaran, P., Liu, Q., Liu, K., ... &

Weinstein, P. (2017). Biodiverse green spaces: a prescription for global urban health. Frontiers in Ecology and the Environment, 15(9), 510-516.

Africa, J. K. Forest Bathing and the Larger Implications of Accessible Nature.

Flohr, C., Tuyen, L. N., Lewis, S., Quinnell, R., Minh, T. T., Liem, H. T., ... &

Williams, H. (2006). Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. Journal of allergy and clinical immunology, 118(6), 1305-1311.

Gilbert, J., & Knight, R. (2017). Dirt is Good: The Advantage of Germs for Your Child's Developing Immune System. St. Martin's Press.

Young, S. L., Sherman, P. W., Lucks, J. B., & Pelto, G. H. (2011). Why on earth?: Evaluating hypotheses about the physiological functions of human geophagy. The Quarterly review of biology, 86(2), 97-120.

Bloomfield, S. F., Rook, G. A., Scott, E. A., Shanahan, F., Stanwell-Smith, R., & Turner, P. (2016). Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Perspectives in public health, 136(4), 213-224.

Slide 9 Summary of diversity

A summary of ‘optimal health' in the ecosystem we call the microbiome. Diversity as the best predictor of health. Characteristics of a diverse microbiome are that it is resistant and resilient. Specific keystone strains are a requirement of this diversity in species to ensure essential functions and crowding of pathogenic bacteria. There are many functions of keystone strains including, maintaining the intestinal lining including up-regulation of tight-junctions and increasing the mucin layer.

See all other sections in reference

Rowland, I., Gibson, G., Heinken, A., Scott, K., Swann, J., Thiele, I., & Tuohy, K. (2017). Gut microbiota functions: metabolism of nutrients and other food components. European journal of nutrition, 1-24.

Slide 10 Eat Clean Get Dirty

Pharmaceuticals are pouring money into recreating next-generation probiotics that take the place of eating a diverse diet and exposure to a diverse regional species pool. We can safely build the microbiome by feeding a varied species-appropriate diet that includes, raw foods, fiber, resistant starch, polyphenols, add diverse local plant matter and appropriate fermented foods while minimizing foods that are irradiated, or made devoid of bacteria (high heat extruded, pasteurization, HPP, etc.)

Exposure to a diverse natural RSP that helps maintain various microbes. Soil-based microorganisms have been shown to be an integral part of the mammalian microbiome. Studies support that exposure to a diverse amount of indigenous plants helps decrease allergic response.

The first step to a diverse microbiome is to reduce or remove the microbiome monsters (antibiotics, pesticide, toxin, processed food, stress, etc.). The second step would be to increase variety of species-appropriate food and exposure to natural green spaces and the regional species pool. Finally, severe cases of dysbiosis may require microbial replacement such as fecal microbiota transplants, FMT, with companies such as Animal Biome (www.animalbiome.com).

It should be noted that a diverse microbiome is created by a diverse amount of whole and minimally processed foods. A variety of processed foods (think ten kinds of potato chips) has not been shown to increase the diversity of the microbiome. Processed foods are correlated with an increase in pathogenic bacteria and LOMD. Preliminary results of processed pet foods (kibble) against a balanced raw diet that includes fiber indicates a greater diversity in the canine microbiome. Whereas, all meat diets, without any roughage, resistant starch, and polyphenols, to feed the beneficial bacteria in the canine gut has been shown to exhibit LOMD.

We are not aware of any studies that test the diversity of the canine microbiome with the RSP on varying canine diets.

Video Microbiome Monsters: https://www.facebook.com/PawsitivelyPrimal/videos/304273450174352/

Human Microbiome Market worth 658 Million USD by 2023. Markets and Markets. Web.

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Herstad, K. M., Gajardo, K., Bakke, A. M., Moe, L., Ludvigsen, J., Rudi, K., ... & Skancke, E. (2017). A diet change from dry food to beef induces reversible changes on the faecal microbiota in healthy, adult client-owned dogs. BMC veterinary research, 13(1), 147.

Li, Q., Lauber, C. L., Czarnecki-Maulden, G., Pan, Y., & Hannah, S. S. (2017). Effects of the dietary protein and carbohydrate ratio on gut microbiomes in dogs of different body conditions. MBio, 8(1), e01703-16.