Introduction to the Gut focusing on MAC and SCFA

1. Introduction to the Gut focusing on MAC and SCFA Judy Csukly

2. Terms used in this discussion Dysbiosis Microbial imbalance or maladaptation Apoptosis Orderly cell death MAC Microbiota accessible carbohydrates…fiber, fruits, and vegetables. SCFA Short-chain fatty acid

3. Butyrate A type of fatty acid that helps your gut work correctly. Butyrates are important as food for cells lining the colon (colonocytes). Without butyrates for energy colon cells would self-digest (autophagy) and die. SCFA which include butyrate are produced by beneficial colonic bacteria (probiotics) that feed on or ferment prebiotics, which are plant products that contain adequate amounts of dietary fiber. These SCFA’s benefit the colonocytes by increasing energy production and cell proliferation, and MAY protect against colon cancer.

4. Commensal Microbiota Living in a relationship in which one organism derives food or other benefits from another organism without hurting or helping it. Microbiota An ecological community of commensal, symbiotic and pathogenic microorganisms found in all multicellular organisms from plants to animals. A microbiota includes bacteria, fungi, viruses and more. Antigens A toxin or other foreign substance that induces an immune response in the body…the production of antibodies.

5. Chemotaxis It is the movement of an organism in response to a chemical stimulus. Cells, and bacteria and other single cell or multicellular organisms direct their movements according to certain chemicals in the environment. Homeostasis The tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.

6. Microbiota Benefits to the host (i.e. You) • Strengthening gut integrity • Shaping intestinal epithelium • Harvesting energy • Protecting against pathogens • Regulating host immunity

7. FACTS • The GI tract (gastrointestinal tract) represents one of the largest interfaces (250-400 square meters) between the host, environmental factors and antigens in the human body. • In an average life time, around 60 tonnes of food pass through the human GI tract. • Gut Microbiota has approximately 10 million genes. • These 10 million genes are shaped by environmental factors, diet, and host genetics.

8. The History of the Microbiota in the GI tract begins • Birth (Vaginal being preferred over C-section for initial inoculation of the GI tract) • After birth it takes around 2.5 years to have a similar GI microbiota as an adult. Children at age 3 can eat just about everything an adult can and slow introduction of foods is no longer a big concern. However the child’s gut is not as stable as the adult. • Illness plays a role in the life events of the gut • Antibiotic treatment (disrupts both short and long term microbial balance) • Diet

9. (natural) History continued • Geographical location: Western vs parts of Africa for example • Surgery • Smoking • Depression, Anxiety, Happiness ( the mind and gut…the second brain) • Living arrangements: urban vs rual (farm life is good for us bring on the germs) *** The exact effects and time for recovery of the microbiota structure is individually dependent

10. The GI microbiota are essential for the synthesis of essential vitamins • Vitamin B12 • Bifidobacteria (folate) • Vitamin K • Riboflavin • Biotin • Nicotinic Acid • Pantothenic Acid • Pyridoxine • Thiamine • Colonic bacteria can also metabolize bile acids *** All of these promote good host health. ***Kefir, sauerkraut, pickles, yogurt…. probiotics help colonize the colon with good bacteria and vitamins

11. The role of GI microbiota health is to • Help maintain the mucosal barrier • Provide nutrients example (vitamins to protect against pathogens) • Interaction between commensal microbiota (those microbiota outside the gut) and mucosal immune system which is crucial for proper immune function.

12. MACs(microbiota-accessible carbohydrates) and SCFAs(short-chain fatty acids)

13. What are MACs? Microbiota-accessible carbohydrates (MACs) are carbohydrates that are resistant to digestion by a host's metabolism, and are made available for gut microbes, as prebiotics, to ferment or metabolize into beneficial compounds, such as short-chain fatty acids (SCFAs)

14. Messages from MAC research • We should Increase dietary fibre, vegetables, and fruit. • You want the food to ferment and produce metabolic end products like short-chain fatty acids and butyrate that are beneficial to us. • The highest level of butyrate is found in the colon. Butyrate is produced by intestinal bacteria from indigestible carbohydrates (MAC’s) such as cellulose and pectin. • This relationship between the colonic bacteria and butyrate has evolved to the extent that butyrate has become the primary source of energy for the colonocytes.

15. New Guy on the Block. • Research suggests that using oral butyrate supplements and butyrate enemas MAY be used successfully to treat inflammatory bowel disease such as Crohn’s and ulcerative colitis!!! • Apple or Broccoli please more money in my pocket!

16. MAC message • Western diet is low in MAC’s but HIGH in carbohydrates and simple sugars. • MAC’s are a main source of energy for gut bacteria so the abundance and variety of MACs can modulate gut microbial composition and function. This, in turn, impacts host immunity and health. • In preclinical studies, MAC (low MAC’s-deprived diet) can create disruption of gut homeostasis, aggravate gut microbiota, gut epithelium, immune cells and the gut barrier. • Also worth considering is the development of inflammatory diseases, such as allergies, infections, and autoimmune diseases.

17. *** Many believe by going on a pseudo gluten-free diet with less white sugar and carbohydrates which are made from flour (i.e. pasta and white bread), they benefit by feeling less pain with a disease such as arthritis. They are not celiac but perhaps the feeling of well being is due to a decrease in the inflammation and the associated pain. A decrease in inflammatory markers. • A decrease in MAC’s can result in a thinner mucus in the distal colon and an expression of heightened inflammatory markers.

18. SCFA(short-chain fatty acid)

19. SCFA • Regulate immune system and inflammatory response • They are decreased in the aged population • Modulate appetite • Regulation and energy intake via receptor mediated mechanisms • Regulate hepatic lipid • Glucose homeostasis

20. SCFA • Regulates butyrate (this is the most important job for SCFA’s) which is known for its anti inflammatory and anti- cancer activities and is an important energy source for colonocytes…important • SCFA’s are rapidly absorbed by epithelial cells in the GI tract where they are involved in the regulation of cellular processes such as gene expression, chemotaxis, differentiation, proliferation and apoptosis(normal cell death)

21. *** Butyrate is produced from carbohydrates via glycolysis (the metabolic pathway that converts glucose C6H12O6, into pyruvate) ****A decrease in SCFA output is evident in individuals consuming a LOW MAC Diet Can we than presume that by increasing the MAC’s we also improve the SCFA’s? I would say YES

22. Thank you and here here to bran, fruits and vegetables with a glass of red wine now and again I may not become obese and it may help with diabetes type two…more food for thought.