Gut Instinct Exploring the Partnership Between You and Your Belly Joanna Wilson, D.O. Women’s Health Board-Certified Internal Medicine

“HUMANS ARE 99% BACTERIAL.” -Bonnie Bassler (TED talk)

Mutualism Humans have 10 X more bacterial cells than human cells Between species live in our intestines – 99% are anaerobes Intestinal bacteria have allowed us to obtain greater nutrients from our food, develop sophisticated immune systems, and the balance affects cognition and emotions

Baby’s First Gift Vaginal flora changes during pregnancy to bacteria which are better able to metabolize breast milk Bacteria introduced during vaginal delivery to germ-free babies establishes the baby’s intestinal ecosystem

Starting with a different set of tools Intestinal bacterial ecosystem introduced to babies born by C- section resembles skin flora of birth participants

Breast Milk is the original pre- and probiotic! Breast milk contains over 600 different kinds of bacteria and it provides oligosaccharides to feed the bacteria in the baby’s intestine. Yum!

Take a peek

A Closer Look at Your Colon Lining

Colon Bacteria: Functions in Nutrition Improve acquisitions of vitamins and nutrients from food – Germ-free rodents required 30% more calories to maintain weight – Malnutrition can occur after antibiotic use Affect cholesterol metabolism Generate vitamins B1, B7, K

Ground Cover The dominant microbiota is established in infancy and inhibits colonization by pathogens by – Occupying luminal cell receptors – Releasing bacteriostatic and microbicidally acting substances

Colon Bacteria: Function in Immunity Assist in establishment of self vs non-self recognition – Germ-free mice have higher numbers of natural-killer cells, with resultant increase in asthma and IBD Mediate activity of the immune cells of the colon lining and control the intestinal lining permeability Communicate with spleen and liver to control immune cell response

Abnormal Immune Response to Gastrointestinal Bacteria May Contribute to Diseases Autoimmune Diabetes I Crohn’s Disease Ulcerative Colitis

Sanitized Society

Societal Behaviors Impact Future Disease The drastic increase of children born without h. pylori gastric bacteria correlates very strongly with the increase in incidence of allergies and asthma in children Children born by C-section have a higher rate of allergies and asthma

Central Nervous System Priming 40 genes for learning, memory, mood, and motor control are permanently affected by the early presence of gut bacteria Timing is everything – Bacteria must be established early in life for benefits to occur

Mood and Colon Bacteria Several studies showed germ-free mice who were inoculated with specific bacteria generated and delivered neurotransmitters to the brain, affecting anxiety, corticosteroid production, and colitis symptoms Human studies using yogurt with probiotics showed emotion and sensitivity were statistically different when probiotics were consumed

Colon Bacteria Alter Pain Perception Pain perception was reduced in rats with Bifidobacterium infantis inoculation Lactobacillus acidophilus induced opiod and cannabinoid receptors in intestinal epithelial cells

Bidirectional Communication Methods Vagus (10 th cranial nerve) Bloodstream (cytokines, hormones, neuropeptides) Spinal cord Allow for near-instant reaction to acute change in gut environment

Neurotransmitters are Highly Preserved in Nature Greatest concentration of serotonin is the intestines!

BacteriaNeurotransmitter Produced Lactobacillus, BifidobacteriumGABA Escherichia, Bacillus, Saccharomyces Norepinephrine Streptococcus, Escherichia, Enterococcus Serotonin Bacillus, SerratiaDopamine LactobacillusAcetylcholine

Stress and The Belly Stress increases permeability of the gut lining to bacteria and bacterial antigens – Activates immune response – Changes the composition of the gut microbiome – Alters brain neurochemicals – Ex: inflammation promotes E. coli proliferation

Highly Processed Diets Modify Colon Bacteria Sugar/sugar substitutes High-fructose corn syrup Preservatives Processed grains Alcohol Appear to be either non-nutritive or harmful to gut flora

Supplements Change Colon Flora Isoflavones for menopause symptoms changed bacterial diversity and composition L-carnitine for muscle gain induces colon bacteria which convert it into a substance which causes atherosclerosis – The same manner as a high red meat diet does

Age and Sex Differences in Colon Bacteria Aging causes: – Reduction in anaerobes and bifidobacteria – Increase in Enterobacter and endotoxin-producing gram negative bacteria Stool pH is higher in women (less acidic)

Effect of Occupation on Colon Bacteria Ranchers harbored more Prevotella species – Abundant in cattle and sheep

Enterotypes- Microbiota Profiles 1. Bacteroides- induced by a diet high in animal protein, amino acids, and saturated fats 2. Prevotella- induced by a diet high in carbs/sugars 3. Ruminococcus

An Individual’s Microbiota is Generally Consistent Through Life Foundation colonies tend to be consistent over a person’s life About 40% of bacterial types are transient and affected by diet, lifestyle, meds

Leanness, Bacteria Type, and Calorie Absorption Lean Bacteroidetes Lower energy absorption Obese Fermicutes Higher energy absorption

Effects of Diabetes and Obesity on Colon Bacteria 26 Species of bacteria correlated significantly with obesity, insulin resistance, and metabolic syndrome Bacteria from obese people had relatively higher production of short chain fatty acids – Increased production of leptin Increases appetite

Thin to Fat Inoculation of genetically thin mice with enterobacter cloacae caused weight gain

Fat to Thin Gastric Bypass Surgery Alters Gut Flora – Fecal samples from bypassed colonized mice to sterile non-surgerized mice caused significant weight loss in recipients

Future Treatments of Obesity Using bacterial flora to change nutrient metabolism and inflammation – Changing to a lower fat/ lower carb diet – Human stool transplants from lean donors

StrainHuman data Strain Human Data L. rhamnosus GGImmune enhancement, infectious diarrhoea in children, primary prevention of atopic dermatitis B. lactis BB-12Immune enhancement, diarrhoea in children L. reuteri SD2112Reduced absences from work, diarrhoea, immune function B. infantis 35624Irritable bowel syndrome (IBS) L. casei DN Immune enhancement B. longum BB536Allergy symptoms, intestinal micro-ecology L. acidophilus NCFMSymptoms of lactose intolerance, reduced small-bowel bacterial overgrowth B. lactis HN019 (DR10)Immune enhancement, especially in elderly B. animalis DN Normalizes intestinal transit time L. plantarum 299VIBS, post-surgical gut nutrition Lactobacillus casei Shirota YIT9029Superficial bladder-cancer recurrence, intestinal microbiota, immune enhancement L. salivarius UCC118Inflammatory bowel disease L. johnsonii La1 (Lj1)Immune function, Helicobacter pylori eradication Escherichia coli Nissle 1917Immune function, intestinal health Saccharomyces cerevisiae (boulardii) lyoAntibiotic-associated diarrhoea, Clostridium difficile infections S. thermophilus (most strains)Symptoms of lactose intolerance

Probiotic Probiotics are live microorganisms which, when administered in adequate amount, confer a health benefit on the host – Not all strains confer the same benefits – Colony Forming Units (CFU) dose varies for effectiveness – Bacteria must be able to survive ingestion – The effect of a probiotic is likely site-specific in the colon – Sauerkraut, kimchi, pickles, yogurt, kefir, miso (nonpasturized) – May not have long-term impact without significant diet change

Prebiotic Selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health – Resistance to degradation by the host – Fermentation by intestinal microbes – Stimulate growth or activity of intestinal microorganisms – Breast milk, leek, asparagus, Jerusalem artichoke, artichoke, garlic, onion, wheat, oat, soybean, bran, psyllium – Fructooligosaccharides (FOS), galactooligosaccharides (GOS)

New Products May Encourage Residence of “Good Bacteria”

Fecal Transplants Highly effective in resistant C. difficile colitis Safe and inexpensive

Future Uses Of Colon Bacteria To Improve Health Create intestinal bacteria which promote endocrine functions, like insulin production Produce highly selective, non- absorbable antibiotics Invent drugs to alter bacteria- to-bacteria communication Understand probiotics to manipulate health and disease Transplant stool from thin people for treatment of obesity Improve nutrient absorption to end starvation