Sunday, May 6, 2018

Talking Points for Microbiome Education

Simple Guidelines for Teaching About Our Microbiome
R. H. Bennett Ph.D. Applied Life Sciences LLC
As the information about the microbiome explodes, it is easy for myths to arise.  This listing may help keep us focused on what we know for sure and what remains a matter of scientific speculation.   These are very general expressions that we will be amended as the science becomes more certain.
IS ….
§  Natural and critically important to almost all aspects of human physiology
§  More of us than our own cells; bacteria outnumber our cells
§  Mostly in the colon (The skin, mouth and other places have their own)
§  Very involved in metabolism and the harvesting of food energy from soluble fiber (Fatty acid synthesis)
§  Significantly disrupted by antibiotic usage (effects can last months to years)(4)
§  Utilizes soluble fiber as the  preferred energy source (aka prebiotics)(10)
§  A complex ecosystem with thousands of member species and interactions
§  Dynamic and often declines over the course of a lifetime; not true in all cultures
§  Essential for healthy immune functions body-wide (Immune cells and mediators constantly migrate out from the colon)(18)
§  Begun at birth in normally delivered infants (Stressed and C-section infants often receive special probiotics)
§  Nourished by colostrum (colostrum factors,  prebiotics, lactose) and milk
§  Subject to imbalances, aka dysbiosis from common and poor dietary habits(19,23,24)


·      A new body system we can afford to ignore
·      Simple in how it works and amenable to simple cause and effect explanations
·      Impervious to the effects of diet, prescription drugs, and alcohol excess
·      Bacteria that are just waiting to harm us
·      Resistant to the ill effects of dietary sugars and fats
·      Maturing and a getting stronger with age after about the first 5 years
·      Readily and easily manipulated to treat diseases  (science is a long way off on therapy; the role of the MB is wellness homeostasis)
·      Contagious, (however we can acquire MB microbes from the environment, and others including pets)


ü  Its work predominantly in the Colon (10)
ü  Synthesize some important factors necessary for our physiology ex. Vit. K, Short Chain Fatty Acids (10,)
ü  Promotes gut integrity to control harmful leakage (6,17)
ü  Competes with and inhibits members that can do harm (13,14,17)
ü  Helps to control opportunistic infections from food and waterborne microbes (33)
ü  Promotes healthy rate of passage (regularity) (5)
ü  Rapidly responds to diet both beneficially and detrimentally (2,3,8,19,21,23,24,25,27)
ü  Respond  favorably to dietary probiotics that are human adapted (HATS) (12,15,36)
ü  Regulate and modulate the immune response (1,18,19,4029)
ü  Influence mood and sense of well being (20,26)

ü  Function significantly in the stomach or small intestine (10)
ü  Digest food or enzymatically aid in the assimilation of major nutrients, Proteins, Carbohydrates or fats (10)
ü  Control internal parasites ex.ed hookworm (40)
ü  Produce non-specific antibiotics (13)
ü  Colonize or grow on the skin (skin has its own MB) (7)
ü  Influence body odor. (40)
ü  Change significantly during regular constipation (28)

Annotated Citations
1.      Arnolds, K. L. and C. A. Lozupone (2016). "Striking a Balance with Help from our Little Friends - How the Gut Microbiota Contributes to Immune Homeostasis." Yale J Biol Med 89(3): 389-395.
a.      Gut microbes, through both molecular factors (such as capsular components) and by-products of their metabolism (such as Short Chain Fatty Acids (SCFAs)), can influence both innate and adaptive components of the immune system, in ways that can drive both effector, and regulatory responses.

2.      Beaumont, M., et al. (2017). "Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans." Am J Clin Nutr 106(4): 1005-1019.
a.      This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis.

3.      Bibbo, S., et al. (2016). "The role of diet on gut microbiota composition." Eur Rev Med Pharmacol Sci 20(22): 4742-4749.
a.      A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides.

4.      Blaser, M. J. (2016). "Antibiotic use and its consequences for the normal microbiome." Science 352(6285): 544-545.
a.      The fourth edge of the antibiotic sword remained unappreciated until recently, i.e., the cost that an antibiotic exerts on an individual's own health via the collateral damage of the drug on bacteria that normally live on or in healthy humans: our microbiota. These organisms, their genes, metabolites, and interactions with one another, as well as with their host collectively, represent our microbiome. Our relationship with these symbiotic bacteria is especially important during the early years of life, when the adult microbiome has not yet formed.

5.      Cassani, E., et al. (2011). "Use of probiotics for the treatment of constipation in Parkinson's disease patients." Minerva Gastroenterol Dietol 57(2): 117-121.
a.      This pilot study showed that a regular intake of probiotics can significantly improve stool consistency and bowel habits in Parkinson's disease patients.

6.      Cui, Y., et al. (2017). "Lactobacillus reuteri ZJ617 maintains intestinal integrity via regulating tight junction, autophagy and apoptosis in mice challenged with lipopolysaccharide." Oncotarget 8(44): 77489-77499.
a.      Live probiotics are effective in reducing gut permeability and inflammation. Collectively, our results indicated that ZJ617 could protect LPS-induced intestinal barrier dysfunction via enhancing antioxidant activities and tight junction and attenuating apoptosis and autophagy via mTOR signaling pathway. These findings could serve as systematic mechanisms through which probiotics promote and maintain gut homeostasis.

7.      Cundell, A. M. (2016). "Microbial Ecology of the Human Skin." Microb Ecol.
a.      The skin provides a range of habitats with different microbiota associated with the three major regions of the skin, namely the moist axilla, perineum, and toe webs; oily or sebaceous head, neck, and trunk; and dry forearms and legs.

8.      De Filippis, F., et al. (2016). "High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome." Gut 65(11): 1812-1821.
a.      High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet.

9.      DuPont, H. L. (2016). "Review article: the antimicrobial effects of rifaximin on the gut microbiota." Aliment Pharmacol Ther 43 Suppl 1: 3-10.
a.      Although definitive studies on the effect of rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation).

10.   Flint, H. J. (2012). "The impact of nutrition on the human microbiome." Nutr Rev 70 Suppl 1: S10-13.
a.      Diet-derived carbohydrates that are not fully digested in the upper gut, known as nondigestible carbohydrates, provide a major source of energy for bacteria that colonize the human large intestine. It is well established that dietary intake of nondigestible carbohydrates influences microbial fermentation and total bacterial numbers in the colon. Recent evidence from molecular ecology has also shown that the amount and type of nondigestible carbohydrates (e.g., resistant starch, non-starch polysaccharides, and prebiotics) influences the species composition of the intestinal microbiota both in short-term dietary interventions and in response to habitual long-term dietary intake.

11.   Foster, J. A., et al. (2017). "Stress & the gut-brain axis: Regulation by the microbiome." Neurobiol Stress 7: 124-136.
a.      The importance of the gut-brain axis in regulating stress-related responses has long been appreciated. More recently, the microbiota has emerged as a key player in the control of this axis, especially during conditions of stress provoked by real or perceived homeostatic challenge. Diet is one of the most important modifying factors of the microbiota-gut-brain axis.

12.   Ganji-Arjenaki, M. and M. Rafieian-Kopaei (2018). "Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review." J Cell Physiol 233(3): 2091-2103.

13.   Garcia-Gutierrez, E., et al. (2018). "Gut microbiota as a source of novel antimicrobials." Gut Microbes: 1-57.
a.      In this review, we summarize some of the antimicrobial compounds that are produced by bacteria isolated from the gut environment, with a special focus on bacteriocins. We also evaluate the potential therapeutic application of these compounds to maintain homeostasis in the gut and the biocontrol of pathogenic bacteria.

14.   Hornung, B., et al. (2018). "Studying microbial functionality within the gut ecosystem by systems biology." Genes Nutr 13: 5.
a.      Intestinal microorganisms, often collectively referred to as intestinal microbiota, contribute significantly to our daily energy uptake by breaking down complex carbohydrates into simple sugars, which are fermented to short-chain fatty acids and subsequently absorbed by human cells. They also have an impact on our immune system, by suppressing or enhancing the growth of malevolent and beneficial microbes. Our lifestyle can have a large influence on this ecosystem. What and how much we consume can tip the ecological balance in the intestine. A "western diet" containing mainly processed food will have a different effect on our health than a balanced diet fortified with pre- and probiotics. 

15.   Hu, S., et al. (2017). "Dietary Additive Probiotics Modulation of the Intestinal Microbiota." Protein Pept Lett 24(5): 382-387.
a.      Probiotics are commonly used dietary additives where they provide the host with many beneficial functions, such as modulating intestinal homeostasis and promoting gut health. These beneficial effects of probiotics may accrue from the inhibiting the growth of pathogenic bacteria and promoting the growth of beneficial flora in the gastrointestinal tract. Probiotics colonization and its impact on gut microbiota members are highly species specific. Different probiotics have been shown to have dramatically different capacities of modulation physiological function..

16.   Imhann, F., et al. (2016). "Proton pump inhibitors affect the gut microbiome." Gut 65(5): 740-748.
a.      The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.

17.   Jandhyala, S. M., et al. (2015). "Role of the normal gut microbiota." World J Gastroenterol 21(29): 8787-8803.
a.      Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

18.   Kim, C. H. (2018). "Immune regulation by microbiome metabolites." Immunology.
a.      Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules.

19.   Kumari, M. and A. L. Kozyrskyj (2017). "Gut microbial metabolism defines host metabolism: an emerging perspective in obesity and allergic inflammation." Obes Rev 18(1): 18-31.
a.      With more than 13% of the world population currently living with obesity and one out of 10 children diagnosed with asthma, we explore here the recent developments in the biosynthesis and mode of action of the key metabolites in relation to these two chronic inflammatory conditions.

20.   Lawrence, K. and J. Hyde (2017). "Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing." PLoS One 12(6): e0179017.
a.      Manipulating gut bacteria in the microbiome, through the use of probiotics and prebiotics, has been found to have an influence on both physical and emotional wellbeing. There was also a striking reduction in negative symptoms related to cognition, memory and emotional wellbeing, including symptoms of anxiety and depression. Dietary gut microbiome manipulations may have the power to exert positive physical and psychological health benefits, of a similar nature to those reported in studies using pre and probiotics.

21.   Li, D. Y. and W. H. W. Tang (2017). "Gut Microbiota and Atherosclerosis." Curr Atheroscler Rep 19(10): 39.
22.   In particular, we critically examine recent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics.

23.   Lin, L. and J. Zhang (2017). "Role of intestinal microbiota and metabolites on gut homeostasis and human diseases." BMC Immunol 18(1): 2.
a.      In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction

24.   Logan, A. C., et al. (2016). "Immune-Microbiota Interactions: Dysbiosis as a Global Health Issue." Curr Allergy Asthma Rep 16(2): 13.
a.      Here, we make the argument that dysbiosis (life in distress) is ongoing at a micro- and macro-scale and that as a central conduit of health and disease, the immune system and its interface with microbiota is a critical target in overcoming the health challenges of the twenty-first century.

25.   Lyu, Q. and C. C. Hsu (2018). "Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites?" mSystems 3(2).
a.      The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases. Chemical compounds in diet also shape the gut flora.

26.   Mayer, E. A., et al. (2014). "Brain-gut microbiome interactions and functional bowel disorders." Gastroenterology 146(6): 1500-1512.
a.      Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota.

27.   Morais, C. A., et al. (2016). "Anthocyanins as inflammatory modulators and the role of the gut microbiota." J Nutr Biochem 33: 1-7.
a.      The health benefits of consuming fruits that are rich in polyphenols, especially anthocyanins, have been the focus of recent in vitro and in vivo investigations. Thus, this review examines studies involving the action of the anthocyanins that are present in many fruits and their effect in the modulating the inflammatory process associated with the interaction between the host and the gut microbiota. The findings of both in vitro and in vivo studies suggest a potential antiinflammatory effect of these compounds, which seem to inhibit activation of the signaling pathway mediated by the transcription factor NFkappaB. This effect is associated with modulation of a beneficial gut microbiota, particularly an increase in Bifidobacterium strains.

28.   Parthasarathy, G., et al. (2017). "Reproducibility of assessing fecal microbiota in chronic constipation." Neurogastroenterol Motil 29(10): 1-10.
a.      The intraindividual reproducibility of fecal microbiota in constipated patients is high and comparable to healthy participants. For most purposes, evaluating the fecal microbiota in a single stool sample should generally suffice in adequately powered studies of healthy and constipated patients.

29.   Postler, T. S. and S. Ghosh (2017). "Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System." Cell Metab 26(1): 110-130.
a.      The human gastrointestinal tract is populated by a diverse, highly mutualistic microbial flora, which is known as the microbiome. Disruptions to the microbiome have been shown to be associated with severe pathologies of the host, including metabolic disease, cancer, and inflammatory bowel disease. Mood and behavior are also susceptible to alterations in the gut microbiota. A particularly striking example of the symbiotic effects of the microbiome is the immune system, whose cells depend critically on a diverse array of microbial metabolites for normal development and behavior.

30.   Schippa, S. and M. P. Conte (2014). "Dysbiotic events in gut microbiota: impact on human health." Nutrients 6(12): 5786-5805.
a.      The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders.

31.   Turnbaugh, P. J. (2017). "Microbes and Diet-Induced Obesity: Fast, Cheap, and Out of Control." Cell Host Microbe 21(3): 278-281.
a.      We showi that a diet rich in fat and simple sugars alters the gut microbiome in a manner that contributes to host adiposity.

32.   Valeur, J., et al. (2016). "Oatmeal porridge: impact on microflora-associated characteristics in healthy subjects." Br J Nutr 115(1): 62-67.
a.      The results suggest that oatmeal porridge has an effect on gut microbial functions and may possess potential prebiotic properties that deserve to be investigated further.

33.   Vogt, S. L. and B. B. Finlay (2017). "Gut microbiota-mediated protection against diarrheal infections." J Travel Med 24(suppl_1): S39-S43.
a.      Human epidemiological studies and experimental infections of laboratory animals both demonstrate that antibiotic treatment can alter the gut microbial community and thereby reduce colonization resistance against diarrheal pathogens. Further research might lead to the development of next-generation probiotics that could be used to bolster colonization resistance and thus prevent travellers' diarrheal.

34.   Xu, J., et al. (2017). "Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota." Med Res Rev 37(5): 1140-1185.
a.      Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs.

35.   Yang, B. G., et al. (2017). "Alterations in Gut Microbiota and Immunity by Dietary Fat." Yonsei Med J 58(6): 1083-1091.
a.      After intake of high-fat diet or Western diet, extensive changes in gut microbiota have been observed, which may be an underlying cause of alterations in whole body metabolism and nutrient homeostasis.

36.   Yin, X., et al. (2017). "Dietary perturbations alter the ecological significance of ingested Lactobacillus plantarum in the digestive tract." Sci Rep 7(1): 7267.
a.      Metagenome predictions supported the premise that L. plantarum dampens the effects of diet on the microbiome. This strain also consistently altered the predicted genetic content in the distal gut by enriching for genes encoding glyosyltransferases and bile salt hydrolases. Our findings demonstrate the interactions between ingested, transient probiotic bacteria and intestinal bacterial communities and how they can differ depending on host diet.

37.   Yoon, M. Y. and S. S. Yoon (2018). "Disruption of the Gut Ecosystem by Antibiotics." Yonsei Med J 59(1): 4-12.
a.      Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.

38.   Zinocker, M. K. and I. A. Lindseth (2018). "The Western Diet-Microbiome-Host Interaction and Its Role in Metabolic Disease." Nutrients 10(3).
a.      We argue that the Western diet promotes inflammation that arises from both structural and behavioral changes in the resident microbiome. The environment created in the gut by ultra-processed foods, a hallmark of the Western diet, is an evolutionarily unique selection ground for microbes that can promote diverse forms of inflammatory disease.

39.   Zou, S., et al. (2018). "Dysbiosis of gut microbiota in promoting the development of colorectal cancer." Gastroenterol Rep (Oxf) 6(1): 1-12.
a.      Recent studies show that perturbations in the microbiota may influence physiology and link to a number of diseases, including colon tumorigenesis. Colorectal cancer (CRC), the third most common cancer, is the disease resulting from multi-genes and multi-factors, but the mechanistic details between gut microenvironment and CRC remain poorly characterized. Different bacterial species and their metabolites play critical roles in the development of CRC. Also, microbiota is important in the inflammatory response and immune processes deregulation during the development and progression of CRC.

40.   Authors Note:  No references could be found in this regard.

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