Dear Julie,

It seems like you cannot open a magazine these days, whether it be a scientific journal or Newsweek, without seeing something on the microbiome or probiotics. Companies are profiting heavily from the sale of supplements and foods containing “good belly bugs shown to improve our health”. The hype that surrounds the exploding microbiome research far exceeds the scientific validation of many of the claims made by internet gurus. Indeed, we are just at the tip of the iceberg in our understanding of how our lifetime partners, the trillions of bugs that live in and on on, affect us. Last week we started a 3 part series on dysbiosis. This week, we will define dysbiosis again, and with the help of my mentor and colleague Dr. Alex Vasquez, we will dive into a better understanding of scientific terms, descriptions, and mechanisms surrounding dysbiosis that we as nutrition leaders should be aware of. Please see the two articles recently published below as examples of media embracing the microbiome:

https://www.sciencealert.com/your-eye-has-a-microbiome-too-and-when-it-gets-out-of-whack-problems-arise

https://www.newsweek.com/prob-eye-otic-therapy-bugs-eyeballs-treat-diseases-1445172

DYSBIOSIS: definitions, descriptions, and mechanisms

Dysbiosis: A relationship of non-acute, non-infectious host-microorganism interaction that adversely affects the host.

Dysbiosis subtypes (based on location): 1) Orodental, 2)Sinorespiratory, 3)Gastrointestinal, 4) Genitourinary, 5) Parenchymal, tissue, blood- including mostly bacteria and viruses, 6) Cutaneous, 7) Environmental, 8) Microbial

Multifocal dysbiosis: A clinical condition characterized by a patient’s having more than one foci/location of dysbiosis; generally the adverse physiologic and clinical consequences are additive and synergistic.

Polydysbiosis: Concurrent dysbiosis with different microbes

Microbial molecules, mechanisms, morphology:

1. Gram-negative bacterial products, LPS
2. Gram-positive bacterial products
3. L-form, pleomorphic, “cell wall- deficient” bacteria
4. Immunostimulation by bacterial DNA, viral DNA, and bacteriophage DNA
5. Superantigens
6. Antimetabolites
7. Beneficial metabolites and molecular signatures

Pathophysiologic responses:

1. Damage to the intestinal mucosa
2. Activation of inflammatory pathways-Toll-like receptors (TLR), NFkB, DAMP, inflammasome
3. Mitochondrial hyperpolarization, mTOR activation
4. Molecular mimicry, cross-reactivity
5. Enhanced presentation of autoantigens
6. Bystander activation
7. Haptenization and the formation of neoautoantigens
8. Immune complex formation and deposition
9. Insufficiency dysbiosis
10. Microbial allergy, hypersensitivity
11. Inhibition of detoxification
12. Bacterial and fungal proteases impair immune defenses
13. Immunosuppression via gliotoxins
14. Mold toxins- mycotoxins
15. Biofilms
16. Impairment of mucosal digestion
17. Central sensitization, microbiome-gut-brain axis
18. Dysbiosis-induced endocrine dysfunction
19. Microbe-induced epigenetic changes
20. Altered vitamin D metabolism and reception

From Vasquez, A. Human Microbiome and Dysbiosis In Clinical Disease. 2014. ICHNFM.org

CAUSES OF DYSBIOSIS 

Antibiotics: Of all the factors that can impact upon the GIT microflora, antibiotics have the greatest detrimental effect. Research using culturing techniques suggested quantitative changes could last up to 40 days after one round of antibiotics. Metabolic derangements can last up to 18 months. New research using more sensitive molecular analysis techniques (RNA) has revealed the presence of antibiotic resistant microorganisms for up to 4 years post-treatment. (Jernberg et al, 2010)(Cotten, 2012) Alterations can last significantly longer than previously believed; 18-24 months after the use of clindamycin and 4 years after triple therapy for H. pylori. Some organisms never recover.

Stress: Stress induces changes to GIT motility and secretions. Also, increases in the circulation of the stress hormone norepinephrine acts a a growth inducer to potentially pathogenic members of the microflora.

Caesarean Section Delivery: C-section babies have been shown to have a different microbiome. Biascucci et al, 2010 showed bifidobacteria present in 56.6% of vaginally delivered infants at day 3 vs 0% of c-section infants. Disturbance in the gut microbiome of c-section babies has been found to last for at least 6 months (Grolund et al, 1999).

Birth Location: Home vs hospital birth can influence the microbiome. Term infants who were born vaginally at home and were breastfed exclusively seem to have the most beneficial gut microbiota. (Highest numbers of bifidobacteria and lowest numbers of C. difficile and E. coli.) (Penders et al. 2006)

Formula Feeding: Formula-fed infants vs exclusively breastfed infants are more often colonized by E.coli, C. difficile, and Bacteroidia fragilis. (Penders et al. 2006)(Morelli, 2008). Counts of these microorganisms are also significantly higher. There is also the presence of different bacterial species.

Diet:

1. Sulphates and Sulphites: Ingested sulphate and sulphite compounds are often added to foods as preservatives (dried fruits, dehydrated vegetables, shellfish, packaged fruit juices, baked goods, most junk foods, white bread, and the majority of fermented alcoholic beverages). These cause the growth of sulphate reducing bacteria which increases hydrogen sulphide production and therefore causes intestinal hyperpermeability and the inhibition of colonocyte metabolism.
2. High Protein Diets: Protein can be fermented by members of the microbiota (putrefaction), with the production of potentially harmful metabolites.

The more protein consumed, the more indoles, phenols, hydrogen sulphide, and ammonia produced (Macfarlane &Macfarlane, 1995)(Magee et al, 2000). Phenol and indole production may be attenuated by an increased fibre intake (Macfarlane & Macfarlane, 1995) via decreases in colonic pH from short chain fatty acid production.
The production and toxicity of colonic ammonia can be attenuated through prebiotic consumption (Genoese et al, 2006)(Weber, 1997).

High protein diets also induce changes to the ecosystem such as decreases in fecal concentrations of bifidobacteria (50% decline on a high-protein + low-carb diet in just 4 weeks). (Duncan et al, 2007) Decreases in concentrations of butyrate-producing species are also seen. All of these changes can be attenuated through prebiotic consumption.

3. High Fat Diets: high fat diets are associated with increases in the ratio of gram-negative to gram-positive bacteria which causes an increased proportion of lipopolysaccharide-containing microbiota in the gut (LPS), which means a greater pool of luminal endotoxin. (Cani et al, 2008) Meals high in fat increase endotoxin absorption wherein postprandial endotoxemia causes low-grade systemic inflammation. (Laugerette et al, 2011) The higher the fat content the higher the serum level of endotoxins. Saturated fat appears to further enhance endotoxin absorption (Mani et al, 2013), whereas omega-3 fats attenuate postprandial endotoxemia. Concurrent consumption of fiber (30 g) also attenuates postprandial endotoxemia (Ghanim et al, 2012)
4. Refined Carbohydrates: Diets high in refined carbohydrates have been shown to slow intestinal transit time which means increased exposure to potentially toxic bowel contents. Refined carbohydrates also alter colonic gas metabolism which may mean changes in the species composition of the flora. A decrease in SCFA production and an increase in colonic pH is also observed. Diets low in fiber increase fermentation of the protective layer of mucin and peptides/proteins, due to the limitation in food sources (fiber/resistant starch) which compromises the mucosal defense and increases production of toxic putrefaction products. This causes direct contact between colonic cells and bacterial products and antigens which leads to inflammation and increased mucosal permeability.
5. Artificial Sweeteners: Sucralose consumption causes significant changes in the microflora such as the following: reductions in beneficial bacteria such as bifidobacteria and lactobacilli and reductions in total anaerobes and aerobes. It also causes increased fecal pH. (Abou-Donia et al, 2008)

Next week we will complete our 3 part series on dysbiosis by discussing ways to diagnose and treat it…..stay tuned and eat your fiber and produce!