Selected Articles on Microbiome and Leaky Gut Syndrome

Intestinal Permeability (also known as the Leaky Gut Syndrome)

  1. Possible Links between Intestinal Permeablity and Food Processing: A Potential Therapeutic Niche for Glutamine - "Increased intestinal permeability should be largely improved by dietary addition of compounds, such as glutamine or curcumin, which both have the mechanistic potential to inhibit the inflammation and oxidative stress linked to tight junction opening."
  2. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer - "...the initial breach of the intestinal barrier function caused by zonulin can be perpetuated by the inflammatory process..."
  3. Human zonulin, a potential modulator of intestinal tight junctions - "While it is well accepted that tight junctions are dynamic structures, surprisingly little is known about their regulation. The discovery of Zot has shed some light on the intricate mechanisms involved in the modulation of the intestinal paracellular pathway and has allowed us to identify an intestinal mammalian analogue that participates in tight junction regulation."
  4. Intestinal Permeation and Gastrointestinal Disease - "...contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn’s disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism."
  5. Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases - "The permeability of the intestinal epithelium depends on the regulation of intercellular TIGHT JUNCTIONS. Tight junctions were originally conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. The contribution of the paracellular space of the gastrointestinal tract to the trafficking of macromolecules between the environment and host was therefore judged to be negligible. Research carried out in the last decade has changed this paradigm, and it has been demonstrated that tight junctions are made up of a complex meshwork of proteins, the interaction of which dictates their competency. ...It is now apparent that tight junctions are dynamic structures that are involved in developmental, physiological, and pathological processes. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of several diseases, particularly autoimmune diseases."
  6. Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3 - "Increased intestinal permeability appears to be an early biologic change that precedes the onset of autoimmune diseases, including CD and type I diabetes.8,23,24 The peculiarity of CD is that it is the only autoimmune disease for which the triggering environmental factor gliadin is known."
  7. Intestinal permeability defects: Is it time to treat? - "...some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of “leaky gut syndrome,” which encompasses a range of systemic disorders."

Gut, Microbiota, Immune System

  1. Gut Microbiota in Health and Disease - "Gut microbiota now appears to influence the host at nearly every level and in every organ system, highlighting our interdependence and coevolution. Its adaptation to our changing life-styles (such as diet- and ethnicity-associated differences in gut microbiota composition) is astounding, highlighting that the consequences of our behaviors affect not only the environment without, but also that within us."
  2. Gut Flora in Health and Disease - "Gut microbiota now appears to influence the host at nearly every level and in every organ system, highlighting our interdependence and coevolution. Its adaptation to our changing life-styles (such as diet- and ethnicity-associated differences in gut microbiota composition) is astounding, highlighting that the consequences of our behaviors affect not only the environment without, but also that within us."
  3. The Impact of Diet and Lifestyle on Gut Microbiota and Human Health - "The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system."
  4. Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms - "Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating."
  5. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour - "Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour."
  6. The Gut Microbiome and the Brain - "The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve."
  7. Diet and the development of the human intestinal microbiome - "Genetics, mode of birth, infant feeding patterns, antibiotic usage, sanitary living conditions and long term dietary habits contribute to shaping the composition of the gut microbiome. This review focuses primarily on diet, as it is one of the most pivotal factors in the development of the human gut microbiome from infancy to the elderly."
  8. Exploring the influence of the gut microbiota and probiotics on health: a symposium report - "...the gut microbiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy..."
  9. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation - "Probiotics may restore the composition of the gut microbiome and introduce beneficial functions to gut microbial communities, resulting in amelioration or prevention of gut inflammation..."
  10. Microorganisms with Claimed Probiotic Properties: An Overview of Recent Literature - "The human microbiota is getting a lot of attention today and research has already demonstrated that alteration of this microbiota may have far-reaching consequences. One of the possible routes for correcting dysbiosis is by consuming probiotics."
  11. The Microbiome Revolution - "...the microbiome affects physiologic functions at each life stage as a participant in life cycle events and processes. During early life development, as the microbiome transforms, it gains diversity and complexity, maturing into an adult-type pattern. This transformation occurs in parallel with host metabolic, immunologic, and cognitive development and undoubtedly contributes to normal physiology. Perturbation could thus have important deleterious consequences. After reproductive life wanes, the selection on the microbiota differs, with important consequences for diseases."
  12. Deciphering the tête-à-tête between the microbiota and the immune system - "Among the microbiota’s major contributions to host physiology is regulation of the development and maintenance of the immune system. There are now a handful of examples of intestinal commensal bacteria with defined immunomodulatory properties, but our mechanistic understanding of how microbes influence the immune system is still in its infancy. Nevertheless, several themes have emerged that provide a framework for appreciating microbe-induced immunoregulation."
  13. A common origin for immunity and digestion - "The gut evolved in a sea of microbes, which posed new challenges and provided new opportunities for nutrition (7). In its most primitive stages, the gut would have provided a new niche that allowed or even invited colonization by microbes. Hosts had to contend with these microbes, either through indifference, forming beneficial associations, eating them, or controlling them to reduce microbial-mediated damage and/or competition for nutrients. While both invertebrates and vertebrates possess innate immune functions, only the latter have adaptive immunity. For this reason, it is thought that the evolution of the immune system paralleled the evolution of the gut, with immunological complexity emerging to protect an increasingly sophisticated digestive tract. In contrast, this essay proposes the alternative view that innate immune defense and digestion were indistinguishable in the primitive gut."