Diseases are rooted in the gut, a fact I have highlighted my whole career. When we understand the profound ramifications, we stop hacking at the leaves and beating around the bush. Understanding this explains why disparate, seemingly incongruent issues are related. For example, long term antibiotics increase the risk of heart disease. Hugo Rodier, MD
Is ‘Leaky Gut’ the Root of All Ills?
Medscape – May 23, 2019.
“Everyone loves a simple answer to a complex problem, so it’s probably not surprising that “leaky gut syndrome” is such a popular catchall diagnosis, at least on the Internet. As the theory goes, the intestinal mucosal barrier becomes increasingly permeable, allowing harmful toxins and bacteria to enter the bloodstream and cause havoc throughout the body. Many blame this digestive disorder for everything from depressionand eczema to fibromyalgia and more.
The trouble is that “leaky gut syndrome” is not recognized by the established medical community, and it’s not listed among the thousands of diagnoses in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). However, it’s related to just enough actual evidence to make it intriguing.
Although researchers have begun to outline the potential role of increased intestinal permeability in several disorders, primarily gastrointestinal conditions, their findings are more nuanced than anything you’ll find on the Internet about “leaky gut syndrome.”
One of the key reasons we’re hearing so much about the intestinal barrier is because, relatively speaking, we’re just beginning to understand how it functions, said Alessio Fasano, MD, W. Allan Walker chair of pediatric gastroenterology and nutrition at Massachusetts General Hospital in Boston.
“Until recently, we were under the impression that the gut barrier is made of single layers of cells that were thought to be almost cemented to each other,” Fasano said. “This vision changed in the early 1970s when a Japanese research group demonstrated for the first time that the spacing between cells is not static but dynamic, and it can be modulated by the presence of structures called ‘tight junctions.'”
“These tight junctions are structured to allow for a natural give-and-take within the intestine,” said Gail Hecht, MD, chief of gastroenterology and nutrition at Loyola University Chicago. “Tight junctions are very highly regulated to let things in and keep other things out,” added Hecht. “This keeps the intestine from acting like a sieve where all kinds of things can just pass through.” The tight junctions maintain the balanced permeability that our health depends upon, keeping harmful antigens and microorganisms from affecting our immune system while simultaneously allowing the passage of water, nutrients, and ions required for our survival.
However, certain circumstances can cause these tight junctions to allow greater outflow, which is sometimes referred to as “leaky gut” even in the academic literature. Hecht and other experts believe this term can be misleading, implying that something is malfunctioning in the body; usually, increased permeability is a natural response that causes no adverse effects. Our immune systems are conditioned to deal with intestinal permeability outside the range of what is deemed normal, according to Jerrold Turner, MD, PhD, professor of pathology and medicine at Harvard Medical School. It only seems to be problematic when increased intestinal permeability accompanies other underlying conditions. “Disease is a vicious cycle in someone who already has a mucosal immune regulatory defect that causes an immune disease, throwing in increased intestinal permeability might just be enough to ignite the fire again.”
Comment: we have known about Leaky Gut for decades. We also have Leaky Arteries, Lungs and Brain—any tissue or organ that becomes inflamed and oxidized will leak.
The gut microbial ecosystem in inflammatory bowel diseases
J. Nature 2019;569:655
“Inflammatory bowel diseases (IBD) include Crohn’s disease and ulcerative colitis. They affect several million individuals worldwide. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease. Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. The study’s data are available through the Inflammatory Bowel Disease Multi’omics Database.” Comment: Irritable Bowel Syndrome is also caused by an unbalanced microbiome. The Brain-Gut Axis is also at play—inflammatory conditions are worsened by stress.
The vaginal microbiome and preterm birth
J. Nature Medicine May 29th 2019
“The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes ‘omics’ data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. Findings highlight new opportunities for assessment of the risk of preterm birth.”
Comment: this means that a microbiome challenged by poor diets, pesticides, acid-blocking drugs and antibiotics increases the risk of premature deliveries.
Host–microbe dynamics in prediabetes
J. Nature 2019;569:663
“Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. First, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host–microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signaling.”
Comment: prediabetes, diabetes and obesity are also inflammatory conditions. Inflammation starts in the gut because our microbiome is 2/3 of our immune system.
Long-term Antibiotic Use Tied to Higher CVD Risk
Medscape – May 09, 2019.
“Investigators followed close to 36,500 female participants in the Nurses’ Health Study (NSH) who were free of CVD at baseline over an 8-year period. After adjustment for demographic, lifestyle, medical, and medication-related covariates, they found that women 60 years or older who took antibiotics for 2 months or more had the greatest risk for CVD, but long-term use of antibiotics was also associated with increased cardiovascular risk if taken by women at midlife (40–59 years). Women who take antibiotics for long periods, especially during more recent adulthood — such as in middle and late adulthood — had a higher risk of CVD in later life.”
Comment: antibiotics trigger inflammation by disrupting microbiome. That inflammation “leaks” out of gut and affects cardiovascular system, as well as all organs. Altered “Postbiotics”, or food by-products produced by an unbalanced microbiome, are also inflammatory.
Glucosamine Supplements Linked to Lower Cardiovascular Events
Medscape – May 14, 2019.
“People who regularly take glucosamine supplements appear to have a moderately lower risk for cardiovascular disease (CVD) events, results from 22 centers participating in the UK Biobank suggest. Glucosamine use was associated with a 15% lower risk for total CVD events and a 9% to 22% lower risk for stroke, coronary heart disease (CHD), and CVD death after adjustment for age, sex, body mass index, race, lifestyle factors, diet, medications, and other supplements. “Even though the use of glucosamine is related to only 15% reduced risk, the effect size is similar to most of the protective dietary factors.”
Comment: glucosamine is an anti-inflammatory molecule. Any anti-inflammatory food or agent will help any inflammatory condition, be it arthritis or heart disease
Mediterranean Diet May Keep Late-Life Depression at Bay
Medscape – May 21, 2019.
“SAN FRANCISCO — Adherence to a Mediterranean diet may guard against late-life depression. Investigators from Hellenic Open University in Patras, Greece, found that for older individuals who adhered to a Mediterranean diet, the likelihood of developing depression was significantly decreased. “The truth is, there are very few studies investigating the impact of adherence to the Mediterranean diet in later life. Up until now, they have largely focused on mid-life, so this is one of the first studies focusing on an older population, and these results suggest the Mediterranean diet may affect the likelihood of depression, regardless of age,” principal investigator Konstantinos Argyropoulos, MD, PhD, told Medscape Medical News. The study was presented at the American Psychiatric Association (APA) 2019 annual meeting.”
Comment: food for thought.
Lower-fat diet rich in fruits, vegetables, and grains may lower risk of death from breast cancer
“The Washington Post (5/15, McGinley) reports that in “the latest analysis of the federally funded Women’s Health Initiative,” researchers found that “women who followed a lower-fat diet rich in fruits, vegetables and grains had a lower risk of dying from breast cancer than those on a higher-fat diet.” The findings are scheduled to be presented at the American Society of Clinical Oncology’s annual meeting. The AP (5/15, Marchione) reports that the study found that “healthy women who modified their diets for at least eight years and who later developed breast cancer had a 21% lower risk of dying of the disease compared to others who continued to eat as usual.” But, “that risk was small to start with and diet’s effect was not huge, so it took 20 years for the difference between the groups to appear.”
Comment: cancer is 85% environmental. Eating well and avoiding environmental toxins may reduce the risk of cancer by 2/3.
