The Diligent Digestive Tract
The digestive tract is solely responsible for harvesting nutrients from the food we eat, and nutrient status certainly depends on digestive health. But the digestive tract is far more than just a “food tube.” Besides digestion, it also is home to about 70 percent to 80 percent of the body’s immune cells and more than 100 million neurons — collectively referred to as the gut-associated lymphoid tissue, or GALT, and enteric nervous system, or ENS, respectively. The digestive tract also contains the intestinal microbiome and serves as a protective barrier between everything that exists in our “inner tube” — including microbes, undigested food particles, hormone metabolites and microbial endotoxins — and the rest of the body. It does so through a highly sophisticated mechanism involving an intestinal barrier that is only one cell layer thick, which is meant to let nutrients in and keep almost everything else out. The health and integrity of that intestinal barrier may have profound influences on diverse systems of the body, including the cardiovascular, neurological and immune systems.

Intestinal Permeability and Leaky Gut
Intestinal permeability refers to the ability of relatively large molecules to pass or “leak” through tight junctions into circulation, hence the term “leaky gut.” Both the intestinal epithelial cells, or enterocytes, and the spaces between them serve as gatekeepers, selectively allowing certain molecules (such as vitamins, minerals and other nutrients) to pass through. Cell membranes allow passage of specific molecules via diffusion or receptor sites, and tight junction, or TJ, complexes bind enterocytes together and regulate the space between them, allowing very few molecules to pass.

When TJ complexes misfire and become less tight, the contents of the digestive tract are able to slip between intestinal enterocytes and make their way through the mucosa layer and into the blood stream. A sugar permeability test may be used to measure TJ integrity, which involves consuming mannitol and lactulose dissolved in water. The ratio of the sugars in a person’s urine can indicate that permeability of the intestines has occurred.

Since the mucosa layer is full of immune cells, increased permeability can trigger an immune response. This is the mechanism behind increased intestinal permeability and the inflammation and immune system activation it may cause, collectively referred to as “leaky gut syndrome.” Now, researchers are seeking to shed light on the link between leaky gut syndrome and several diseases and disorders.

Permeability Consequences
Undigested food, bacteria, yeast and their metabolic waste products, known as microbial endotoxins, are examples of molecules that are meant to remain within the digestive tract but can enter the lamina propria mucosal layer (connective tissue where GALT resides) and, ultimately, the blood stream through permeable TJs. When these molecules pass through TJs, they are called antigens, which the body perceives as harmful irritants. “Antigen-presenting” immune cells patrol for invaders in the lamina propria, recognize the antigens and trigger an inflammatory cascade. A steady stream of antigens passing through the TJs keeps that inflammatory cascade going, resulting in chronic low-grade inflammation, which may have a negative effect on overall health. In fact, research has found the inflammatory response itself may increase gut permeability, continuing a vicious cycle.

The migration of antigens from the digestive tract to the blood stream, paired with inflammation and immune system activation, may trigger the development of several health issues. For example, immune activation from gut-derived microbial endotoxins and food antigens have been associated with autoimmune disease and psychiatric disorders, including major depression, bipolar disorder, schizophrenia and autism.

Could There Be Leaky Brain Syndrome?
A growing body of animal and human research suggests the intestinal microbiome interacts with the central nervous system, possibly through the blood-brain barrier, or BBB, and that gut dysbiosis — an imbalance between good and bad microbes — may be a causal factor in many central nervous system, or CNS, conditions. Like the intestinal barrier, the BBB is formed by endothelial cells and tight junctions that line cerebral blood vessels, selectively allowing nutrients in and toxins and metabolites out of the brain to maintain optimal interstitial fluid for the CNS, while also protecting against circulating infections. Inflammation from a variety of causes is known to disrupt the BBB, which can expose the brain and CNS to harmful compounds in circulation. Some research has found a compromised BBB to be a key feature in neurological diseases, especially those that also involve immune activation, including multiple sclerosis, brain cancers, and Parkinson’s and Alzheimer’s diseases.

The connection between the gut microbiome and the BBB is not well understood, but researchers propose it could be mediated by the immune system. Gut bacteria are known to release compounds into the blood stream that can affect the CNS, either by crossing the BBB or interacting with BBB cells. Furthermore, these inflammatory molecules increase both intestinal and BBB permeability, while short-chain fatty acids such as butyrate, made by gut bacteria, have been shown to improve both intestinal and BBB permeability.

Blood Vessel Permeability and Cardiovascular Health
In addition to “leaky gut” and “leaky brain,” there is evidence from human and animal studies that blood vessel endothelium also can become permeable. The endothelial glycocalyx, or eGC, is a layer of hair-like macromolecules on the endothelial cells of blood vessels. It regulates endothelial function, and its dysfunction may be linked with early physiological changes in vascular permeability and clotting cascades that precede conditions including edema, hypertension, sepsis, Type 2 diabetes and atherosclerosis. Microbial endotoxins, free radicals and inflammatory cytokines can damage the eGC.

A microbial endotoxin called lipopolysaccharide, or LPS, has been investigated for its potential role in the development of cardiovascular disease. Research suggests LPS from intestinal bacteria may damage endothelial cells, oxidize LDL cholesterol and encourage the release of proinflammatory cytokines, all of which may contribute to atherosclerosis. This could mean intestinal permeability and the translocation of bacteria and their endotoxins may contribute to systemic inflammation, atherosclerosis and cardiovascular disease. Research already exists that links bacterial translocation from oral bacteria with atherosclerotic plaques and coronary artery disease, and the gut microbiome may be another source of bacteria and endotoxins that fuel chronic inflammation.

An Opportunity for Nutrition Intervention
We may not yet know if or which foods influence the tight junctions of the BBB and blood vessel endothelium, but there is limited human and animal research suggesting certain eating patterns, nutrients and lifestyle factors can help support healthy TJ function in the gut, including flavonoids, probiotics, prebiotics, glutamine, curcumin, gluten avoidance by those with celiac disease and non-celiac gluten sensitivity, and zinc supplementation by those with Crohn’s disease. Some research has found certain factors may have the potential to trigger TJ dysfunction and “leakiness” in the gut including food allergies and sensitivities, dysbiosis, alcohol use and Western dietary patterns.

At first glance, it may not be obvious to target digestive health in people with cardiovascular or neurological disease, but research suggests it could be a potential opportunity for nutrition intervention. As research continues to emerge, it likely will uncover major unknowns that could change the way we think about health and the interaction between distant organ systems. While more research in humans is needed to shed light on how to harness the connectivity between the gut microbiome, CNS and immune system to maximize health and healing, existing research gives registered dietitian nutritionists some interesting food for thought.

References

Al-Asmakh M, Hedin L. Microbiota and the control of blood-tissue barriers. Tissue Barriers. 2015;3(3): e1039691.
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. 2015;7(1):a020412.
Hall H. Leaky Brain, Leaky Gut: Are They Real? Science-based Medicine website. Published November 20, 2018. Accessed June 19, 2019.
Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3.
Joneja, JV. The Health Professional’s Guide to Food Allergies and Intolerances. 1st ed. Chicago, IL: Academy of Nutrition and Dietetics;2013.
“Leaky Gut Syndrome.” NHS website. Reviewed September 3, 2018. Accessed June 19, 2019.
Lee B, Moon KM, Kim CY. Tight Junction in the Intestinal Epithelium: Its Association with Diseases and Regulation by Phytochemicals. J Immunol Res. 2018:2645465.
Logsdon AF, Erickson MA, Rhea EM, Salameh TS, Banks WA. Gut reactions: How the blood-brain barrier connects the microbiome and the brain. Exp Biol Med. 2018;243(2):159–165.
Ma Y, Yang X, Chatterjee V, Meegan JE, Beard RS Jr, Yuan SY. Role of Neutrophil Extracellular Traps and Vesicles in Regulating Vascular Endothelial Permeability. Front Immunol. 2019;10:1037.
Małkiewicz M, Szarmach A, Sabisz A, Cubała W, Szurowska E, Winklewski P. Blood-brain barrier permeability and physical exercise. J Neuroinflammation. 2019;16(1).
Manahan B. A brief evidence-based review of two gastrointestinal illnesses: irritable bowel and leaky gut syndrome. Altern Ther Health Med. 2004;10(4):14.
Mu Q, Kirby J, Reilly CM, Luo XM. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017;8:598.
Obrenovich MEM. Leaky Gut, Leaky Brain?. Microorganisms. 2018;6(4):107.
Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345–359.
Rogler G, Rosano G. The heart and the gut. Eur Heart J. 2014;35(7):426-430.
Rudzki L, Szulc A. “Immune Gate” of Psychopathology-The Role of Gut Derived Immune Activation in Major Psychiatric Disorders. Front Psychiatry. 2018;9:205.
Serra e Silva Filho W, Casarin RC, Nicolela EL Jr, Passos HM, Sallum AW, Gonçalves RB. Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients PLoS One. 2014;9(10):e109761.
Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit Care. 2019;23(1):16.
Van Spaendonk H, Ceuleers H, Witters L, et al. Regulation of intestinal permeability: The role of proteases. World J Gastroenterol. 2017;23(12):2106–2123.
Xhima K, Weber-Adrian D, Silburt J. Glutamate Induces Blood–Brain Barrier Permeability through Activation of N-Methyl-D-Aspartate Receptors. Journal of Neuroscience. December 7, 2016. 36 (49) 12296-12298; DOI:10.1523/JNEUROSCI.2962-16.2016.
Yoo BB, Mazmanian SK. The Enteric Network: Interactions between the Immune and Nervous Systems of the Gut. Immunity. 2017;46(6):910–926.

Although my father and most of his immediate family came to the U.S. well before the Iranian revolution, the rest of our extended family came in droves after the revolution in 1979. I often wonder if this is why many of us refer to ourselves as Persian rather than Iranian, referring to the rich history and ancient cultural ties to prerevolutionary Iran and the land that used to make up the Persian Empire.

When I think about Persian dishes I have enjoyed throughout my life, my memories swirl around big family get-togethers and Shabbat dinners. I can close my eyes and conjure up the intoxicating scents of savory herbs mingling with buttery rice. Today, the vast majority of Persian Americans live in Los Angeles, aka “Tehrangeles,” including most of my father’s side of the family. When we visited my grandparents, aunts and uncles, cousins and an enormous extended family, the first stop upon arrival was always my grandparents’ condo in the Westwood neighborhood, a Persian-American hub. My grandmother always had something cooked and ready for us, and the heavenly smell would envelop us as soon as we stepped out of the 11th-floor elevator. The aroma of seasoned rice, chicken soup and gondi, a Persian-Jewish dumpling made of chicken or turkey and chickpea flour (our version of the matzo ball), was like a cozy hug welcoming us inside.

Late-night dinners at relatives’ homes featured so many dishes, we couldn’t possibly taste them all — but oh, how we tried. In Persian culture, food and hosting are synonymous with love, and “the more, the merrier” are words we live by. Since Persian families tend to be large and close-knit, even the most casual get-togethers can grow into big events with music, sometimes dancing and singing, and masses of food.

The most well-known and well-loved dishes are universal, as are the ubiquitous fragrant rice and stews. A typical Persian dinner includes seasoned, roasted chicken; at least two khoresht (stews) and different kinds of rice — always chelo (plain white rice) and at least one kind of seasoned rice. Also served are salad; a sabzi platter of fresh herbs and radishes; and the crowning glory of Persian rice dishes, tadig.

The centerpiece of the meal — the most anticipated dish of all — is literally found at the bottom of the pot. If you use a nonstick pot and pour extra oil into the rice as it steams (and if you’re lucky), the rice at the bottom slowly fries to become a beautiful, crunchy golden disk.

People take great pride in presenting their rice disk when it comes out in one whole piece. Sometimes, thin slices of potato are placed at the bottom of the pot, where they fry embedded in crunchy rice. My mother adds whole coriander seed for a delicious pop of floral flavor in each bite. There’s no time for niceties when tadig hits the table — it will be gone in the blink of an eye. It can be enjoyed on its own or you can flip the tadig on your plate crunchy-side-down and spoon khoresht on top, then sprinkle with sumac, our goes-on-everything spice.

While the flavor profiles and ingredients in Persian cuisine differ slightly among Jewish and Muslim styles of cooking, several key seasonings are central to all Persian cuisine:

Za’faran (saffron), also known as red gold, is the most expensive spice by weight; ounce for ounce, it is pricier than gold. Iran produces about 90 percent of the world’s saffron, which is used sparingly to impart a slightly astringent flavor and golden hue to foods. It is most commonly used in making chelo and usually appears in the center of the tadig. Saffron should be crushed and then “bloomed” (brewed) to release its full flavor.

Limoo omani (dried lime) is quite possibly the most important flavoring used in Persian (and Iraqi) cooking. It looks like a dark shriveled ball and offers a unique sour-bitter taste. It is used both whole and ground as a coarse powder. When used whole in stews, limoo omani softens during cooking and can be pressed to release more of its tart flavor. A brave few (myself included) pluck it out of stew and eat it whole.

Sumac is made from a ground berry and has a citrusy, tangy flavor that brightens and highlights food. It is added to white rice, stews (especially ghormeh sabzi), bread and butter, feta, hummus and more.

Advieh means “spice” in Farsi and is a blend of aromatic spices similar to garam masala or five-spice seasoning. While several variations exist, advieh contains some combination of turmeric, cinnamon, cardamom, cumin, cloves, black pepper and sometimes dried rose petals. Different combinations are used for different dishes, and it’s not easy to get Persian cooks to reveal their special blends. Advieh is used sparingly mostly in chicken and rice dishes; about one teaspoon is all you need to transform the dish.

Gol-ahb (rosewater) is another important flavor. Used in nearly all desserts, sometimes in combination with cardamom, it also is delicious and refreshing in hot or iced tea. My favorite use is adding a few drops to watermelon.

My family left Iran but brought the best of Persian culture with it: love of family, dedication to community, the most amazing food — and, wow, do we throw a great party. Nooshe jon (May it nourish your soul)!

References

Monks K. Iran’s homegrown treasure: the spice that costs more than gold. CNN website. Updated September 3, 2015. Accessed February 8, 2019.

Confusion and interest about food’s influence on acid-alkaline balance abound, due in part to popularity among celebrities and non-scientific health enthusiasts who tout versions of an “Alkaline Diet” as a cure-all for a wide range of maladies, from cancer to heart disease. While these types of claims typically are red flags within the health and medical community, as well they should be, there is some research backing health benefits of this eating pattern — making it worth clarifying what an alkaline eating pattern entails and the science surrounding this popular diet.

Before sifting through the evidence, two common points of confusion should be addressed: First, the acid-alkaline balance in question is not that of the blood. The pH of human blood is strictly maintained at about 7.4 (7.35 to 7.45). The lungs and kidneys spare nothing to keep the pH tightly controlled since the consequences of blood pH changes would be life-threatening. It’s more about what the body has to do in order to keep the blood’s pH where it needs to be. The basic premise of an alkaline diet is that what a person eats influences how much compensating the body has to do in response to that meal.

The second point is the concept of a food being “acidic” or “alkaline” in composition, on its own, versus its potential effect on the body. Lemon juice and tomatoes, for example, are acidic. But when ingested, they promote alkalinity. The pH of the actual food does not dictate the net effect on the body. Rather, it’s the “potential renal acid load,” or PRAL, of a food — a value that measures acid excretion in the urine — that determines where it fits within the context of acid-alkaline balance.

Diet and pH

Foods can be categorized by their PRAL as acid-forming or alkaline-forming. Foods that have a negative acid load are considered alkaline (mainly fruits and vegetables), while grains, meats, dairy foods, fish, soda and beer are acid forming, meaning they have a positive acid load.

Eating patterns matter more than specific foods, and healthy acid-forming foods — such as poultry, whole grains and eggs — are not necessarily detrimental but may need to be combined with alkaline-forming foods to make the net effect of the meal either neutral or alkaline. This can be achieved by the time-honored recommendation to eat more fruits and vegetables.

Different systems of the body maintain different pH levels, with some more tightly regulated than others. The pH of each system has a specific function, and certain pH levels may improve certain functions. For example, the stomach maintains a very acidic pH at 1.2 to 3.0 so that it can break down dietary protein and kill ingested pathogens. Fluid inside cells can range between slightly acidic and slightly alkaline, but an alkaline environment within cells (achievable through an alkaline-promoting diet), improves cellular function.

To maintain pH balance, some systems may have to support others. For example, bone matrix contains an alkaline reservoir in the form of calcium and magnesium. Blood contains its own buffering mechanisms, but if there is a very “acidic” dietary load over time and those mechanisms become insufficient, the kidneys may signal the release of buffering minerals from the bone matrix to maintain the blood’s pH.

A high-protein eating pattern increases total acid load, but does not result in a change in blood chemistry or pH. That’s because the kidneys send in mineral buffers, such as calcium phosphate and calcium carbonate, to keep the blood pH at a safe 7.4. However, that same diet also changes urinary chemistry. Urinary magnesium, citrate and pH all decrease, while urinary calcium, uric acid and phosphate increase. Excess protein plus a high PRAL diet may decrease bone density over time if not properly balanced by foods or supplements that are rich in alkali, such as potassium, magnesium and bicarbonate. If there are adequate buffering minerals available, then the body can handle a high acid load from food. But if the diet doesn’t supply enough of these minerals or they become depleted from acidic eating patterns over time, then the body has to pull mineral buffers from their storage depot — the bone matrix. Over time, borrowing these buffers can demineralize bone and increase the risk for kidney stones. This may explain the association between diets high in alkali-rich fruits and vegetables with better bone mineral density.

Effects of Acidic and Alkaline Diet Patterns

Eating patterns high in animal protein, dairy foods and refined grains and low in fruits and vegetables are acid-forming diets with high PRAL. Most Western diets are very low in potassium and magnesium, but high in sodium and chloride. Over time, this can result in diet-induced, low-grade, chronic metabolic acidosis.

In addition, consuming large amounts of sodium may exacerbate dietary metabolic acidosis. High-sodium diets increase conditions that are linked to osteoporosis in women, while dietary potassium balances these effects. Although Western diets are associated with osteoporosis, urinary pH does not appear to predict bone fractures or bone mineral densities in some studies. Other consequences of high-PRAL diet include increased risk for muscle wasting and kidney stone formation — and possibly osteoporosis, although these data are conflicting, so more research is needed to confirm a definitive link.

Alkaline diets — high in potassium, magnesium and bicarbonate from fruits and vegetables — have been found to have a range of potential benefits. Aside from high fruit and vegetable intake being linked with lower rates of osteoporosis, cardiovascular disease, cancer and other chronic diseases, alkaline diets in particular may offer specific benefits.

While the data linking alkaline eating patterns and osteoporosis prevention are mixed, there do seem to be some benefits of alkaline diets in terms of fracture prevention. Alkaline diets have been found to preserve muscle mass in seniors and women, possibly by supplying adequate dietary potassium and magnesium. Since muscle mass is important to fall and fracture prevention, these findings may be significant to bone health. While an alkaline diet increases urine pH, which some assert may reduce urine calcium loss, the effects on bone health remain inconclusive.

An alkaline diet also has been shown to reduce the risk of other chronic diseases, including stroke and hypertension, as well as improve memory and cognitive function. The pH within each cell of the body is responsive to PRAL, and an alkaline pH within the cell improves enzymatic function, which may have health benefits. Furthermore, animal and cell studies indicate that a lower (acidic) pH within cells may support cancer proliferation, but there are no clinical data yet to support those studies.

In light of emerging and ongoing research, and in spite of red flags and confusing celebrity endorsements, nutrition experts may consider keeping acid-alkaline balance on their radars. At its core, an alkaline diet is simply higher in fruits and vegetables, which in itself supports a host of health benefits. And while some versions of alkaline diets recommend avoiding “acidic” foods, such as meats, dairy and grains, a better strategy may be to focus on adequate protein intake — and then simply enjoying an overall healthful eating pattern.

Over time, science slowly moved the needle away from this mindset. “Good” and “bad” serum cholesterol were delineated, and more recently, studies determined that eating cholesterol-rich foods didn’t actually increase serum cholesterol like we once thought. And while some still maintain that lower total serum cholesterol is always best, more recent research challenges the validity of measuring cholesterol as a singular marker of cardiovascular health. So where does the medical community stand now on serum cholesterol?

What is Cholesterol?

First, a refresher. Manufactured by the liver, cholesterol’s functions extend well beyond the cardiovascular system. It’s the structural backbone to sex hormones, including testosterone, estrogen and progesterone (in addition to the adrenal hormone cortisol), and is crucial to brain function, both as part of myelin sheath structure and its role in nerve impulse conductivity. Because it is required to synthesize vitamin D from sun exposure, cholesterol is relevant to the immune and skeletal systems. And in cell membranes, cholesterol provides structural support and may also act as an antioxidant.

There’s even evidence that cholesterol may play a role in protecting against bacterial and parasitic infection.

Serum cholesterol travels through the blood stream within lipoproteins, of which the two most abundant are low-density lipoprotein and high-density lipoprotein. LDL carries cholesterol from the liver to peripheral tissues, while HDL carries cholesterol back to the liver for excretion or recycling. Routine cholesterol panels typically include total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. LDL and HDL cholesterol levels measure the amount of cholesterol carried in these lipoproteins, and many health professionals rely on these figures to gauge risk for cardiovascular and coronary artery disease.

What if “Normal” Does Not Equal “Healthy”?

This is where it gets interesting. Studies have found that up to 75 percent of patients hospitalized for heart attacks had normal to optimal serum LDL levels, and in 2013, revised guidelines from the American Heart Association and American College of Cardiology removed LDL cholesterol target levels and recommended that doctors not prescribe cholesterol-lowering medication based on cholesterol levels alone — a significant departure from long-held advice.

The key to understanding LDL cholesterol’s risks and rewards may lie in the size and density of its particles, which range from large, buoyant, cholesterol-rich particles to small, dense particles low in lipids. Since everyone has a mix of different types of LDL particles at any given time, some practitioners are testing for serum cholesterol “phenotype” patterns to discern composition (see sidebar).

Pattern A describes having mostly large, more buoyant LDL particles and is linked with good cardiovascular health, while pattern B refers to having mostly smaller, more dense LDL particles that are more prone to oxidation — and therefore associated with greater risk of atherosclerosis and higher overall cardiovascular disease risk. So whereas a person with low triglycerides, high HDL cholesterol and slightly elevated total and LDL cholesterol with pattern A phenotype (big, buoyant particles) may not be at increased risk for atherosclerosis or cardiovascular disease, a person with low to normal HDL cholesterol and normal total and LDL cholesterol levels with pattern B phenotype (small, dense particles) may indeed be at increased risk.

LDL particle size and density are influenced by genetics, diet and body weight — and dietary interventions have demonstrated measurable effects. More long-term studies are needed to help shape recommendations, but some researchers are exploring the effect of diet and weight loss on LDL patterns.

While the mechanisms are not yet understood, they include:

• Higher intakes of saturated fat may increase large, buoyant LDL particles.
• Reducing carbohydrates may reduce small, dense LDL particles.
• Reducing dietary fat may reduce total LDL cholesterol, but specifically lowers large, buoyant particles.
• Weight loss has been shown to improve LDL patterns in overweight men.
• A high-carbohydrate, low-fat diet has been shown to shift study participants from pattern A to pattern B.
• Study participants who started out as pattern B on a high-fat diet remained pattern B on a low-fat diet.

Although the clinical value of measuring LDL patterns remains hotly debated, many agree that more research is warranted since findings potentially could change the landscape surrounding serum cholesterol. In the meantime, staying up to date on emerging research and new practices is advice that any practitioner can get behind.

The human microbiome refers specifically to the community of microorganisms that live in and on the human body (or any “host” animal) and their collective genome, which interacts with our host genes. The microbiota (formerly called “microflora”) refers to the microorganisms themselves. Our microbiota are affected by everything from how we entered the world to how much time we spend barefoot. Bacteria, yeasts, molds, dirt and the types of food we eat all impact microbiota, thereby influencing the microbiome.

Gut bacteria aid digestion by breaking down otherwise indigestible plant fibers into short-chain fatty acids that intestinal cells can access. Emerging research also suggests that gut bacteria influence many other metabolic functions, so much so that some experts now regard it as a “hidden” organ system, capable of interacting with its host down to DNA expression. As a result, the microbiome’s role in conditions as varied as irritable bowel diseases, obesity, Type 2 diabetes, depression, autoimmune disorders and Parkinson’s disease is under intense scientific scrutiny. The core questions remain: How does the microbiome become altered in a way that negatively affects the host, and how does a host build better microbiota?

Establishing the Colony

The bacteria that our immune systems recognize as “normal” (the bacteria that will prevail in our guts or the duration of our lives) is established by our first exposure to our mothers’ microbial mix. Babies born vaginally are colonized by microbes present in the birth canal, primarily by strains of Lactobacillus species that differ from non-pregnant women. By contrast, babies born via cesarean section are colonized by the microbiota of a mother’s skin and whatever other bacteria happen to be present at birth, predominantly Staphylococcus species.

First foods matter as well. Breast milk has its own microbiota that differ depending on whether the mother gave birth vaginally or via C-section, possibly due to the antibiotics women receive before and after C-section delivery. Breast milk contains oligosaccharides that act as prebiotics — food for the infant’s developing intestinal community. After birth, infants begin to cultivate their own bacterial mix until the developing microbiota reach a relatively stable state, shaped by environment and diet. By age 2, the child’s microbiota are believed to resemble an adult’s.

An Evolving System

Our microbiome co-evolves with us and influences our metabolism, physiology, nutrition and immune function. Once the microbiome is established, it is believed to be relatively stable throughout a person’s life, although short- and long-term changes can occur. Antibiotics dramatically affect the microbiome. The ability of the microbial residents to bounce back after a round of antibiotics varies greatly among individuals, and multiple rounds of antibiotics can significantly shift the types of microbes that survive. Often this kind of disruption leads to dysbiosis, an imbalance of beneficial and pathogenic bacteria and other microbes.

Dietary changes also significantly alter the microbiome, and preliminary human studies suggest that these changes can occur in as little as three days. Interestingly, while what we eat alters our microbiomes, the microbiota also appear to influence what we choose to eat, as microbes compete for space and nutrients. Researchers suspect that dominant gut microbes trigger cravings for foods that either benefit them or suppress their bacterial competitors.

Microbes may even create dysphoria in the host until the person succumbs to the craving. Researchers propose several possible mechanisms by which this works: Microbes may be able to influence taste receptors, making certain foods taste better; they may spark the release of hunger-triggering hormones; or they may influence eating habits by hijacking the vagus nerve that connects the gut and brain.

Altered microbiota and dysbiosis may be related to many chronic diseases and conditions, including obesity, diabetes, metabolic syndrome, depression and gut diseases. This link appears to be rooted in inflammation, endotoxemia and possibly changes to the immune system, which means treating the gut may be an effective way for registered dietitian nutritionists to address multiple conditions.

Digestive Health, IBS and IBD

Irritable Bowel Syndrome is an increasingly common functional gastrointestinal disorder, the hallmark symptoms of which include abdominal discomfort or pain, distension and bloating, and diarrhea, constipation or a combination of both. Low-grade inflammation and significant dysbiosis are prominent features of this syndrome. While normal gut microbiota prevent pathogenic bacteria from gaining a foothold on the intestinal lining, dysbiosis may allow the bacteria associated with IBS symptoms to thrive, triggering further inflammation by activating the immune system.

People with IBS often experience higher levels of anxiety, stress and depression, as well as higher rates of metabolic syndrome. While the exact cause of IBS remains unclear, some research points to dysbiosis along with dysregulation of the brain-gut axis and autonomic nervous system. IBS and inflammatory bowel disease — including ulcerative colitis and Crohn’s disease — are associated with increased intestinal permeability (sometimes referred to as “leaky gut syndrome”). IBS typically features low levels of beneficial Bifidobacterium bacteria; IBD, which also may be triggered by dysbiosis, features low bacterial diversity. Probiotics have shown to be effective therapeutic interventions for both IBS and IBD, shown to improve intestinal integrity, alleviate symptoms, reduce inflammation and strengthen the intestinal barrier.

Obesity, Type 2 Diabetes and Metabolic Syndrome

Obesity and its consequences are a complex set of syndromes. Lifestyle, diet and exercise habits contribute significantly to this “diabesity” epidemic, though changes to the microbiota also appear to play a role by influencing weight gain and metabolism. From animal studies, we’ve learned that transferring gut bacteria from obese animals to germ-free, lean animals induces obesity and metabolic disease, even when diets are unchanged.

While the relationship of microbiota and weight in humans is less clear, studies have consistently demonstrated dysbiosis in people with Type 2 diabetes. Healthy control subjects tend to have more bacteria that produce the shortchain fatty acid butyrate, and individuals with Type 2 diabetes tend to have higher levels of pathogens, such as Clostridium species, though research has not yet confirmed whether a difference in gut microbes is a contributing factor or an effect. In addition, when pathogen-free microbiota from lean, healthy donors are transferred to patients with metabolic disease, insulin sensitivity improves.

Microbiota and Mood

Lending credence to the gut’s reputation as a “second brain,” it’s been observed that stress and depression are linked with IBS and IBD, and the microbiome also may play a role. Psychological and physiological stress affects the gut in ways that alter the microbiota and foster dysbiosis, bacterial overgrowth and intestinal permeability. These changes trigger inflammation and affect the brain and central nervous system through increased toxic exposures (endotoxins from bacterial metabolites enter the bloodstream through a “leaky gut”) and neurotransmitter disruption. Gut microbes produce hormones and neurotransmitters that are taken up by the human brain.

Preliminary research indicates that changes to the microbiome may affect things such as mood, anxiety, memory and concentration. Rodent studies have found that manipulating the microbiome results in changed behavior. However, while an anti-inflammatory diet could provide some benefit, there aren’t any large-scale human studies that clarify the role of dietary intervention on the central nervous system with respect to changes to the microbiome.

Mind Your Microbes

Amid mounting interest in its influence on human health and disease, attention has turned to therapeutic approaches that target the gut. A diet high in fruit, vegetables and perhaps whole grains allows beneficial bacteria to dominate and inhibits the growth of more harmful strains. While researchers haven’t reached consensus about what constitutes an optimal microbiome, there is some general advice for tending our microbial gardens:

• • Fruit and Vegetables
    A plant-centric diet rich in vegetables, fruit and legumes, and high in dietary fiber and polyphenols, appears to benefit the microbiota. These foods offer intestinal bacteria fuel in the form of prebiotics.
  • Fermented Foods
    While beneficial bacterial strains found in fermented foods may not settle into the gut permanently, they may affect microbiota by influencing the gene expression of the bacteria already there. Naturally fermented foods, such as yogurt and kefir with “live, active cultures,” sauerkraut, kimchi, tempeh and raw vinegar, are high in beneficial Lactobacillus bacteria. To get the benefits, be sure the foods are “lactofermented” or naturally fermented and raw or unpasteurized, as pasteurization kills beneficial bacteria.

• Garden Herbs
  Garlic and leeks contain natural sources of the prebiotic inulin. Garlic also has natural antimicrobial properties, which may help suppress pathogenic bacteria and foster beneficial bacteria growth.
• Focus on Fresh
  Enjoy minimally processed foods and limit sugar and unhealthy fats, especially trans fats. Some studies have associated diets of highly-processed foods with dysbiosis and pro-inflammatory microbiota.
• Probiotic Supplements
  Consider taking a high-quality probiotic supplement (with several different strains of Lactobacillus and Bifidobacterium species, such as L. acidophilus, L. reuteri, B. longum and B. bifidum), particularly during and after antibiotic use to recolonize the digestive tract and help manage antibiotic-induced diarrhea. Since antibiotics kill all bacteria, it is best to take probiotic supplements at least two hours before or after taking antibiotics.

Often compared to the plastic tips on shoelaces, telomeres are non-coding sections of DNA that act as buffers, maintaining the genome’s integrity and protecting chromosomes from fraying. Without telomeres, cells would not be able to replicate properly and genetic material might become attached to each other or rearrange.

Telomeres shorten each time the cell replicates. Once they reach a critical shortness, chromosomes become unstable and the cell dies through apoptosis (programmed cell death). Comparing an individual’s telomere length against a mean for their age group determines if that person’s telomeres are longer or shorter than average. Age, genetics, lifestyle, disease and pharmaceutical drug use all influence telomere length. People with shorter-than-average telomeres may be “aging” more quickly than their same-aged peers with longer telomeres.

Shortened Telomeres, Aging and Disease
Associated with advanced age, shortened telomeres also are found with a number of inflammatory conditions such as Alzheimer’s disease, vascular dementia and atherosclerosis. Cardiovascular disease, hypertension, diabetes, obesity and dementia also have been linked with shorter telomeres. Oxidative stress from tobacco or drug use and exposure to pollution, physiological and psychological stress, micronutrient deficiencies and chronic nutrient insufficiencies all are associated with shortened telomeres.

The relationship between shortened telomeres and cancer is murkier: It’s unclear whether longer or shorter telomeres protect against cancer. In theory, shorter telomeres result in DNA instability, which may trigger the development of cancer. While some types of cancers, including bladder, esophagus, stomach, ovarian and kidney cancers, have been associated with shortened telomeres, no association has been found with skin, endometrial and prostate cancers. Some studies report that telomere lengths are inversely related to overall cancer risk. It’s possible that shorter telomeres help the body suppress tumors if the short telomeres prevent cancerous cells from proliferating, but a few studies have found that cancer cells may be able to maintain longer telomeres.

Lengthening Telomeres through Lifestyle Changes
Many conditions are associated with shorter telomeres, but it’s not clear whether the disease state shortens the telomere or if the shorter telomeres bring about disease. However, research has come closer to identifying behaviors that elongate telomeres, potentially warding off disease and rapid aging.

A small pilot study, among the first intervention studies to determine the effects of lifestyle on telomere length, was published in the September 2013 issue of Lancet. Researchers Dean Ornish, MD, and Elizabeth Blackburn, PhD, reported that a comprehensive lifestyle intervention resulted in elongated telomeres after a five-year study of men with low-risk prostate cancer. The intervention included a low-fat plant-based diet, meditation and stress relief, moderate daily exercise, and time spent with family and friends. Those in the control group had a 3 percent reduction in telomere length after five years, while those in the intervention group increased telomere length by 10 percent.

Because telomeres are so affected by oxidative stress, a plant-based diet high in phytochemicals and antioxidants may be protective. Other studies have found that the following were associated with longer telomeres:

• Nutritional adequacy of nutrients important to methylation, including folate
• Dietary antioxidants such as vitamin C, vitamin E and selenium
• Dietary intake of omega-3 fatty acids from seafood
• Higher vitamin D concentrations, possibly because of its anti-inflammatory effect
• Taking a multivitamin
• Physical activity, especially during leisure time (as opposed to physical activity at work)
• Stress management and meditation

The results of the Ornish and Blackburn study could depict what an overall healthy lifestyle looks like — a combination of healthful diet, exercise, stress relief and time spent having fun.

Detoxification is the biochemical process that transforms non-water-soluble toxins and metabolites into water-soluble compounds that can be excreted in urine, sweat, bile or stool. Because these processes rely on specific nutrients such as flavonoids, minerals, certain amino acids and B-vitamins, there are therapeutic detoxification protocols to support the organ systems through which the body detoxifies.

On the other hand, popular culture teems with detox diet books, fasts, cleanses and products — many fueled by quasi-science and inflated claims of purging the body of toxins without qualifying “toxin” or the mechanisms at play. As a result, much of the medical community eschews the term “detoxification,” dismissing the entire idea as a baseless fad that’s ineffective at best, potentially harmful at worst.

But there is a community of RDs — largely but not exclusively in integrative nutrition — who support reclaiming this word and if not applying nutritional detoxification strategies to promote health and healing, at least clarifying for patients and practitioners what a detoxification diet might look like from a science-based perspective.

Detoxification Decoded

Skepticism of dietary detoxification protocols may lie, in part, in the vernacular. In some cases, it is a clash of figurative language vs. literal meaning. Words such as “purify” or “clean” — used to illustrate a point, much in the way that “heavy” and “light” describe the fat and calorie content of foods as opposed to actual weight — are rejected by some practitioners because they are nonclinical words. Lesser-known phrases such as “toxic load” or “body burden” (which refer to the level of internal and external toxin accumulation in the body) are used by other clinicians and researchers. While this supports the argument for standardized language, in the interest of clarity, this article will identify key phrases or concepts that may vary within the nutrition community.

Biochemically, detoxification occurs through two main enzymatic processes. Phase I detoxification, sometimes called “functionalization” or “activation,” is when oxidation, reduction and hydrolysis reactions turn a fat-soluble toxin into an unstable intermediate molecule, resulting in a free radical (a.k.a. “intermediary metabolite”). Phase II detoxification then converts the intermediate molecule into a more stable, water-soluble one through conversion or “conjugation” reactions. The water-soluble molecule can be excreted through urine, bile and feces.

If the body’s Phase II enzymes can’t keep up with Phase I, the result is too many circulating free radicals. If Phase I mechanisms are not functioning efficiently or can’t keep up with the influx of toxins, then those toxins are not neutralized and continue to circulate or become deposited in bone and soft tissue.

The Nutrition Prescription

A general detoxification diet is based on whole foods and includes fruits and vegetables (preferably organic*) and adequate fiber and water. Some foods and nutrients have been found to be particularly effective in “up-regulating,” or revving up, the body’s detoxification pathways:

• Fruits and vegetables: A diet high in fruit and vegetables contributes a wide range of phytochemicals, many of which promote detoxification enzymes.
• Cruciferous vegetables: Compounds in crucifers such as cabbage, broccoli, collards, kale and Brussels sprouts promote enzymes that regulate detoxification in the liver.
• Turmeric: Curcumin in turmeric has been shown to have anti-inflammatory properties and function as an antioxidant in animal studies.
• Green tea: Known for its antioxidant activity, it has been suggested that green tea’s bioactive components are polyphenols — especially catechins such as epigallocatechin gallate, or EGCG.
• Water: The importance of adequate hydration for detoxification cannot be underestimated. Water facilitates urinary excretion and bowel motility, supports the lymphatic system and replenishes fluids lost through sweat.
• Fibrous foods: Soluble and insoluble fiber, as found in flax seeds, beans, oats and brown rice, can bind to toxins and bile and carry them out of the body through the stool. It can also minimize contact with harmful compounds, such as acrylamides from charred meat, by regulating transit time.
• Probiotics: Beneficial bacteria from probiotic supplements or fermented foods such as yogurt and lacto-fermented vegetables protect the intestines and may inhibit the growth of pathogenic bacteria, which produce ammonia and other toxic metabolites.
• Eggs, garlic and onion: Sulfur supports the body’s production of glutathione, an antioxidant sometimes called “the master detoxifier” because it is a critical nutrient co-factor in Phase I and II detoxification.

Many science-based practitioners are reluctant to consider detoxification a legitimate component of natural health and healing based on the perception that recommendations are, across the board, unscientific. It is true that some popular detox diet and product claims are based on preliminary if not questionable studies, but it’s important to not let healthy skepticism become personal bias as research continues to explore the intricacies of detoxification pathways, nutrigenomics, generational effects of toxic exposure and their effects on human health.

After all, detoxification is not the first diet and health concept to be exploited or oversimplified, nor is it likely to be the last — reinforcing the importance for food and nutrition experts to help consumers separate fact from fiction.

Most research focuses on fermented dairy products. However, vegetables such as cabbages, carrots, garlic, soybeans, olives, cucumbers, onions, turnips, radishes, cauliflower and peppers, in addition to fruits such as lemons or berries, offer novel flavors and textures—partly explaining why home fermentation, and particularly lactic acid fermentation, is becoming an increasingly popular trend. Whether keepers of culinary tradition, those interested in potential health benefits or folks who simply enjoy trying new foods, fermentation enthusiasts are bringing new life to this ancient practice. Lactic acid fermentation, or lacto-fermentation, is among the most common methods and one of the easiest to experiment with at home. It is an anaerobic process whereby lactic acid bacteria, mainly Lactobacillus species, convert sugar into lactic acid, which acts as a preservative. Salt plays a pivotal role in traditional fermentation by creating conditions that favor the bacteria, preventing the growth of pathogenic microorganisms, pulling water and nutrients from the substrate and adding flavor.

Global Cultures

The earliest record of fermentation dates back as far as 6000 B.C. in the Fertile Crescent—and nearly every civilization since has included at least one fermented food in its culinary heritage. From Korean kimchi and Indian chutneys to the ubiquitous sauerkraut, yogurt and cheese, global cultures have crafted unique flavors and traditions around fermentation.

In some cases, fermentation is a critical component to food safety beyond preservation. In West African countries, garri is an important food source. It is made from the root vegetable cassava, which contains natural cyanides and, if not properly fermented, can be poisonous. Other foods, such as the Tanzanian fermented gruel togwa, have been found to protect against foodborne illnesses in regions that have poor sanitation.

Asian civilizations in particular have a history of fermenting a wide variety of foods—Japanese natto (soybeans), Vietnamese mám (seafood), Chinese douchi (black beans), Lao pa daek (fish sauce), Korean banchan (side dishes)—that remain essential components of their everyday cuisine. Fermented foods are also used in Eastern cultures for medicinal purposes, which may be of particular interest to registered dietitians who practice “food as medicine.” Links between fermented foods and health can be traced as far back as ancient Rome and China, and remain an area of great interest for researchers in modern times.

The Science of Probiotics

Evidence-based reviews indicate that certain strains of probiotics contribute to the microbial balance of the gastrointestinal tract—supporting the immune system and reducing inflammation in the gut. Health conditions that can benefit from probiotics therapy include diarrhea, gastroenteritis, irritable bowel syndrome, inflammatory bowel disease and cancer.

However, exactly which probiotic strains, appropriate dosages and fermentation profiles are still being investigated. According to “Probiotics and Prebiotics in Dietetics Practice” in the March 2008 Journal of the Academy of Nutrition and Dietetics, the challenge in developing clinical recommendations for probiotics therapy is not a lack of scientific literature, but a lack of consolidated research and consistency across studies with respect to bacterial strains, dosages and populations. Nonetheless, the authors write that “although documenting efficacy of probiotics is still emerging, a growing number of consumers and health-care professionals are interested in trying probiotics,” and that people might “also be interested in increasing the levels of live active cultures in their diet. Such diets have not been evaluated strictly, but could be recommended based on the emerging body of evidence that a variety of probiotics is beneficial.”

In addition to supporting human health, Lactobacillus and other bacteria may protect against foodborne illness by inhibiting and eradicating foodborne pathogens, including Listeria monocytogenes, Staphylococcus aureus and Bacillus cereus. The inhibition of pathogenic bacteria may be due in part to pH, as well as antimicrobial bacteriocins produced by Lactobacillus to inhibit other competitive strains, including foodborne pathogens. While these findings support fermentation as a safe method of preservation, and consumption of fermented grain has been associated with decreases in foodborne illness, more research is needed.

An Integrative Medicine Perspective

A basic tenet of integrative nutrition is that digestive dysfunction is at the root of most maladies. Research has suggested that an imbalance of beneficial-to-pathogenic bacteria and yeasts can disrupt the delicate intestinal barrier, which constitutes the body’s first line of defense against ingested pathogens. One strategy used by RDs in integrative medicine is the reintroduction of beneficial bacteria to improve digestive function and rebalance the intestinal flora. While probiotic supplementation is widely utilized, many prefer using a “food first” approach by recommending naturally fermented foods.

Small Batches vs. Large-Scale Production

Traditional lacto-fermentation utilizes the microflora present on vegetables and a lactic acid bacteria starter culture (whey). Once upon a time, all pickles were naturally fermented through lacto-fermentation, which is why some people use the terms “pickled” and “fermented” synonymously. In modern times, this is no longer the case. In large-scale food manufacturing practices, vegetables are washed in diluted chlorine solutions to destroy or inactivate existing microflora, and acetic acid (which, along with water, is a main component of vinegar) is used instead of lactic acid. Of the few commercially available pickles that are lacto-fermented, most are heat processed or pasteurized to create a sterile product. Others are “desalted” or rinsed, likely removing any beneficial bacteria that may have been present.

If it’s health benefits you seek, lacto-fermented foods work best from both quality and food safety perspectives when produced in small batches, although there are small-scale operations that pride themselves on reinvigorating the fermented food market (look for them at gourmet stores, farmers markets and Asian shops). Meanwhile, home fermentation enthusiasts continue to look to the past as the wave of the future.

More Resources

• Wild Fermentation: The Flavor, Nutrition, and Craft of Live-Culture Foods (Chelsea Green Publishing 2003)
• Making Sauerkraut and Pickled Vegetables at Home: Creative Recipes for Lactic Fermented Food to Improve Your Health (Alive Books 2002)
• Preserving Food without Freezing or Canning: Traditional Techniques Using Salt, Oil, Sugar, Alcohol, Vinegar, Drying, Cold Storage, and Lactic Fermentation (Chelsea Green Publishing 2003)