About the Author: Dr. Greg Sharon is a board certified allergist-immunologist trained in the treatment of adult and pediatric patients. He was trained at Rush Presbyterian St. Lukes Medical Center in Chicago. He has practiced for over 30 years in the midwest. He uses a variety of treatments i.e. allergy avoidance, education, medications, nutritional consulting, dietary supplements and a holistic approach to help patients overcome their illnesses.
Articles by Greg Sharon MD
The Earth Inside Us (or The Invisible Self)
Asthma and Allergy Center‘s Dr. Greg Sharon examines the old adage “you are what you eat” and the impact our environment has on our health.
The human being has always been defined as an individual organism. However, modern science has shown that we are not truly alone. We, in fact, are not even Human. We are symbionts, or a collection of distinct species that work together or, like any society, sometimes fight as a unit.
“If I were to remove any trace of human cells, you would still be recognizable as you but look like a mist of bacteria, virus, fungus, parasites, and animals all working together to make you,” said Dr. Greg Sharon, the founder of the Asthma and Allergy Center. “We call this collection of disparate microorganisms the microbiome. It consists of microbes that are both helpful and potentially harmful.”
Most non-human organisms are symbiotic (we both benefit) and some, in smaller numbers, are pathogenic (can cause a disease). In a healthy body, pathogenic and symbiotic microbiota coexist without problems in most cases.
The Earth Inside Us Explained
Why does Dr. Greg Sharon say the earth inside us? It is because you are a microsome of the earth itself. The earth and its smallest residents are so important that we may not be able to survive without them.
Not only are you what you eat, you are the world in which you live – and the world which lives within you.
All the science fiction that you read about – how we would discover new worlds in space and colonize the stars – is fantastic, but fantasy. You could leave the earth behind but, over time, you and your microbiome would die in sterile space.
Even if you could travel to other stars, the hurdle is your health not your science.
“Within our bodies exist 100 trillion symbiotic microbial cells,” Dr. Greg Sharon continued. “The main organisms are bacteria in the gut; we need this human microbiome to make use of the genes that these cells harbor. Do you realize that within us there exist fewer DNA codes for enzymes than in the average ear of corn?”
The doctor went on to explain that while we need 200,000 proteins to work in our world, we only have 22,000 within each of us. For example, the Meta-HIT consortium reported a gene catalog of 3.3 million non-redundant genes in the human gut microbiome alone, as compared to the approximately 22,000 genes present in the entire human genome.
So, what is the human microbiome and how do we understand it?
The term, microbiome, was coined by Joshua Lederberg in 2001 and has become an important part of medicine. We say the microbiota when we mean microbial cells associated with humans; and we say microbiome, when referring to the catalog of these microbes and their important genes. In addition, the term “metagenomics” originally referred to shotgun characterization of total DNA found in these cell but, in fact, it is often only a part of the information found in those cells.
When we looked at the gut microbiome, we soon realized we could not culture all the bacteria present there because they were interdependent on their neighbors for food, enzyme and chemical products to survive. Thus, we began to use the studies of marker genes such as the 16S rRNA gene.
“Just as we age, mature, learn, like different foods and interact with new family and friends, the body’s microbiome does the same,” Dr. Greg Sharon explained. “In fact, we are in lockstep with the environment.”
“This is why my medical specialty is different from all other medical disciplines,” Dr. Greg Sharon continued. “We always have looked at the human condition through the effects of the environment. The month you were born, your environment at birth, changes in your diet and even the presence or absence of an animal makes you microbiome different and unique.”
We now know this difference or diversity may have a more powerful effect then previously thought. Studies of the diversity of the human microbiome started with Antonie van Leewenhoek (the microscope guy), who, as early as the 1680s had compared his oral and fecal microbiota. He noted the striking differences in microbes between these two habitats and between samples from individuals in states of health and disease in both sites. Thus, studies of the profound differences in microbes at different body sites, and between health and disease, are as old as microbiology itself.
What is new today is not the ability to observe these obvious differences, but rather the ability to use powerful molecular techniques to gain insight into why these differences exist, and to understand how we can affect transformations from one state to another.
The problem is that the ability to diagnose a disease and the ability to cure a disease may be separated by a thousand years.
Although host-associated microbes are presumably acquired from the environment, the composition of the mammalian microbiota, especially in the gut, is surprisingly different from free-living microbial communities in many ways. Both are interdependent on each other and look for both protection and food as a community, but analysis of bacterial diversity from free-living communities in terrestrial, marine, and freshwater environments – as well as communities associated with animals – suggests that the vertebrate gut is an extreme.
Taking it to the Extreme
Our bacterial communities are like environments typically considered extreme, such as acidic hot springs and hydrothermal vents. This suggests that coevolution between vertebrates and their microbial consortia over hundreds of millions of years has left us with a specialized community of microbes that thrive in the gut’s warm, eutrophic, and stable environment. This is why our microbiome is mostly bacteria. However, small communities of yeast, viruses, and animals do play a role in health and disease. Similarly, the diversity among the microbiome of individuals is immense compared to human genomic variation: individual humans are about 99.9% identical to one another in terms of their host genome, but can be 80-90% different from one another in terms of the microbiome of their hand or gut.
These findings suggest that employing the variation contained within the microbiome will be much more fruitful in personalized medicine, the use of an individual patient’s genetic data to inform healthcare decisions, than approaches that target the relatively constant host genome alone.
“I like to think that our human DNA tells us a story of our past human ancestry,” Dr. Greg Sharon said. “But our microbiome tells us about our present health.”
In nature, microorganisms have an essential role in biochemical cycles, such as nitrogen, phosphorous, and carbon. Microorganisms are vital for nitrogen fixation, assimilation, mineralization, nitrification and denitrification. We humans are constantly exposed to new microorganisms in the environment, which comprises beneficial and pathogenic microbes. We have found that it is not just a specific species we need to survive, but its products. If a species can help us, and not hurt us, we may add it. Unfortunately, there are opportunistic pathogens also associated with the human body that reside as commensals and do not cause diseases under normal circumstances. These are actively looking for opportunities to infect the host and, upon sensing conditions will do so, leading to decreased body immunity. The beneficial microbes protect against colonization of opportunistic pathogens and serve as an essential barrier to reduce human exposure to an infectious or otherwise harmful agent. Any dysbiosis in these dynamics is expected to affect the human health.
“Exploring the relationship between the environmental and human microbiome could improve our understanding of both beneficial and disease-causing microbes,” Dr. Greg Sharon said.
So, let’s take a look at three important factors shaping the world within us: infancy, what each human starts with; digestion and nutrition, what each human introduces into mix; and antibiotics, the proverbial wild card.
The gastrointestinal (GI) tract of a human infant provides a brand-new environment for microbial colonization as we are basically sterile inside our mothers.
Indeed, the microbiota that an infant begins to acquire depends strongly on mode of delivery.
Twenty minutes after birth, the microbiota of vaginally delivered infants resembles the microbiota of their mother’s vagina, while infants delivered via Cesarean section harbor microbial communities typically found on human skin. When I first saw a Cesarean delivery, the old doctors would take some smear from the vaginal vault and then insert it into the infant’s mouth. They believed it helped the infant’s immunity by transferring the microbiome of the mother to the infant. The new doctors thought this practice was nothing more than an old wives’ tale, something without scientific proof, and the practice was largely abandoned.
We now know the science supports the old doctors’ methods. The acquisition of microbiota continues over the first few years of life, as an infant’s GI tract microbiome begins to resemble that of an adult as early as 1 year of life. We know that significant changes in gut microbiota composition are apparent at five key points in a baby’s development: starting a diet of breast milk, development of fever, introduction of cereal, introduction of formula and table foods, and antibiotic treatment and introduction of an adult diet.
Interestingly, each dietary change was accompanied by changes in gut microbiota and the enrichment of corresponding genes. For example, as the infant began to receive a full adult diet, genes in the microbiome associated with vitamin biosynthesis and polysaccharide digestion became enriched. When I trained in the 1970s, we did not use antibiotics in Cesarean sections; during the ’80s we then added it as “prophylaxis;” however, the old doctors would not allow it to run into the mother’s vein until the baby’s cord and, thus, blood supply was disconnected from the mother. Now, in modern times, every C-section has antibiotics, and all are run into the mother – and, therefore, into the unborn infant – before the first incision is even made.
We now know that one change – the introduction of anti-biotics before birth – has led to a major increase in allergy problems in our youth. (The rate of childhood allergies is further exacerbated by the increase in births by Cesarean sections over the past 40 years, but that’s a topic for another article.)
Digestion and Nutrition
We know there is a link between a host’s microbiota, digestion, and metabolism. In an analysis of humans and additional mammalian species, 16S rRNA sequences clustered together carnivores, omnivores, and herbivores into specific community structures differing depending on diets.
“Dietary changes can lead to significant changes in bacterial metabolism, especially small chain fatty acids and amino acids, in as little as one week,” said Dr. Greg Sharon.
Importantly, the genetic diversity found within our gut microbiota allows us to digest compounds via metabolic pathways not explicitly coded for in the mammalian genome, greatly increasing our ability to extract energy from our diverse diets. Gut microbiota also seem to play an important role in obesity. Germ-free mice that receive a transplant of gut microbiota from conventional mice have an increase in adiposity – commonly referred to as obesity – without increasing food intake due to increased energy extraction from the diet and increased energy deposition into host fat cells. We know from studies that the two major microbial divisions, Firmicutes and Bacteriodetes, show different abundances depending on health and weight of the human or mouse. Decreased Bacteriodetes and increased Firmicutes have been found in genetically obese people when compared to their lean counterparts, and the obesity phenotype can even be transferred to a person.
Studies have also shown the altered microbiota somehow makes the mice hungrier, and their microbe-induced obesity can be cured by restricting the amount of food in their cages to that consumed by wild-type mice, as well as by antibiotics.
The correlation between microbes and obesity is perhaps best illustrated through weight loss.
As different groups of human subjects were placed on either a fat-restricted or carbohydrate-restricted diet, their abundance of Bacteriodetes increased as their body weight decreased, transitioning from the signature ‘obese’ microbial community to a ‘lean’ community. Thus, the modulation of a patient’s microbiota might be a therapeutic option for promoting weight loss in obese patients or promoting weight gain in underweight children. Surprisingly, the microbes that we ingest with our food might be providing our individual microbiome with new genes to digest new foods. Thus, microbes have the ability to greatly increase the number of metabolic tools of the human gut, allowing us to digest an array of substrates.
Antibiotics are mainly used to combat pathogenic bacterial species that reside within, or that have invaded a host; however, the current generation of antibiotics are broad spectrum and target broad swaths of the normal microbiota as well. Thus, antibiotics significantly affect the host’s innate gut microbiota.
Let’s take a closer look. Three to four days after treatment with the broad-spectrum antibiotic ciprofloxacin, the gut microbiota experience a decrease in taxonomic richness, diversity, and evenness. The spectrum of bacterial diversity is narrowed significantly, one might even argue significantly different, from what existed prior to treatment. This lasted for months after the drug was stopped.
“Recently, researchers in the UK published findings that any antibiotic usage leads to a greater risk of inflammatory bowel disease in the future,” Dr. Greg Sharon said.
The changes in the gut microbiota demonstrated significant interpersonal variability with antibiotics. While the gut microbiota began to resemble its pre-treatment state a month after treatment, differences between individuals were seen with regards to how closely the post-treatment community resembled the pre-treatment community, and some taxa failed to return to the community. Indeed, the reestablishment of some species can be affected for up to four years following antibiotic treatment. Yet the overall recovery of the gut microbiota following antibiotic treatments suggests that there are factors within the community, biotic or abiotic, than promote community resilience, although these have yet to be elucidated. A recent study showed that the bacterial species may not be as important as what products they supply to the gut. Thus, just looking at the bacterial species in the gut may not give an accurate picture.
Different antibiotics also tend to produce results that differ substantially between subjects – and even body sites. Understanding the factors that determine the ability of a microbiota to resist and recover from antibiotic induced perturbation, as well as understanding the factors that determine its current state, will help us develop tools to assist in microbiome manipulation. One fascinating hint that the microbiota may be more plastic – that is, better able to self-heal – than imagined is the recent success of treatment of persistent Clostridium difficile infections (i.e., diarrhea and colitis) via stool transplant. This treatment has been successful in several studies, and in general the diminished gut community produced during the C. difficile infection is replaced by the transplanted donor community. The success of this technique is remarkable, especially considering how little is known about the best community to supply.
By Greg Sharon MD Allergist Immunologist Published May 2023
Irritable Bowel Syndrome New Concepts
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal ailments among those seeking health care for gastrointestinal disorders. Despite its prevalence, IBS pathophysiology or cause is poorly understood. Hopefully education about this disease will lead to new possible therapeutic targets. In the past decade, there has been increasing focus on the possible connection between increased intestinal mucosal permeability, inflammation, and visceral hypersensitivity. We see increased permeability in subsets of IBS patients. The objectives of this article is to help summarize the role of the healthy intestinal epithelium as a barrier between the lumen and the rest of the body with a focus on tight junctions; to examine the lines of evidence that suggest that different triggers lead to increased intestinal mucosal permeability and disruption of tight junctions in IBS patients; and to explore how this increased permeability may elicit immune responses that affect afferent nerves, resulting in the pain associated with IBS.
irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurrent abdominal pain associated with changes in stool frequency and form, with no recognized underlying pathological or organic etiology. It affects up to 18% of adults in Western countries, women, especially among those seeking health care. IBS has a significant impact on quality of life and health care utilization. IBS subtypes based on bowel dysfunction [diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), alternating stool forms (IBS-A), and unsubtyped.
Traditional management of IBS has been symptom based, but recent developments in the understanding of complex interactions between the gut, immune system, and nervous system have led to an expanded arsenal of therapeutic options for relief of both bowel movement-related symptoms and pain. There is growing interest in the connection between increased intestinal permeability, immune responses, and visceral hypersensitivity, especially as a potential target for therapeutic intervention. In this paper, we will review the role of the healthy intestinal epithelium as a barrier between the lumen and the rest of the body, examine the lines of evidence that suggest that different triggers lead to increased intestinal mucosal permeability, and explore how this increased permeability may elicit immune responses that then affect afferent nerves, resulting in pain.
The Intestinal Barrier
In healthy individuals, the intestinal barrier provides a “gated wall” between the luminal contents of the gut (e.g., food antigens, microflora, ingested bacteria) and the rest of the body, selectively regulating what crosses the epithelium via transcellular transport mechanisms and regulated paracellular permeability. The intestinal barrier is comprised of several defensive layers: 1) the lumen, where gastric acids and pancreatic and biliary secretions degrade bacteria and antigens; 2) host luminal bacteria, which inhibit colonization by pathogens through the production of antimicrobial substances, through modification of the luminal pH and luminal content, and by competing for nutrients that are required for pathogen growth; 3) the microclimate, which includes the unstirred water layer, the glycocalyx, and the mucus layer with secreted IgA and prevents adhesion of pathogenic bacteria to the epithelium; 4) the epithelium, which consists of cells connected to each other via junctional complexes to create a physical barrier and reacts to noxious stimuli with chloride secretion and release of antimicrobial peptides; and 5) the lamina propria. The latter contains components: cells that participate in innate and acquired immunity and secrete immunoglobulins and cytokines; the enteric nervous system and endocrine system; myofibroblasts; and other components.
Increased Permeability in IBS
Intestinal permeability can be tested by multiple techniques. The four primary modes often used to explore permeability in IBS are: 1) following the absorption and urinary secretion of molecules (oral probes) known to be unchanged in urine and whose site of intestinal absorption is known, such as polyethylene glycol, the saccharides mannitol, lactulose, and sucralose, or chromium-labeled EDTA (51Cr-EDTA); 2) examining the migration of a probe across mucosal biopsies in vitro; 3) studying the effects of biopsy extracts or colonic supernatants from IBS patients (compared with healthy controls) when applied to intestinal epithelial monolayers, such as Caco-2 monolayers, or murine intestinal tissue (in vivo or in vitro); and 4) analyzing expression levels of TJ proteins by immunohistochemistry, immunofluorescence, or mRNA quantitation. Each technique has its own strengths and weaknesses.
By Greg Sharon MD Allergist Immunologist Published January 2023
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Dr. Sharon is a board certified Allergist/Immunologist who founded the Asthma and Allergy Center, a full-spectrum allergy and immunology center for patient care, in 1991. To make an appointment to meet with the experts at Asthma and Allergy Center, Contact Us today.