THE AGING GUT
MANAGE YOUR GUT HEALTH TO STAY YOUNGER AS YOU AGE
"From the moment of birth, the human body plays host to a rich diversity of microbes. Body sites such as the skin, the gut and the mouth support communities of microorganisms (collectively known as the microbiome) that are both numerous and diverse. As our understanding of the microbiome advances, it is evident that these microbial populations participate in a multitude of symbiotic associations with us. The disruption of these associations can lead to a range of diseases beyond mere pathogenesis as microbial nutrition, signaling, and immune defense break down. It is known that changes in microbial composition occur as the human host ages and that diet and living conditions influence the microbiome of older individuals." From the 2015 book, Frailty in Aging (The Biology of Frailty: Frailty and the Microbiome)
As many of you know from following my blog, GUT HEALTH is everything. No matter what specific health issue you or a loved one may be dealing with, give me a couple of minutes and I'll find studies (plural) tying it back to Gut Health. Unfortunately, as we age we go through a process that the medical community has termed 'senescence'. Senescence refers to the age-related molecular and metabolic deterioration that is relentless attacking all of us, as well as the inability of the body's cells to divide, repair, regenerate, and heal. Although this process affects everyone who lives long enough, it doesn't take long to realize that different people go through senescence quite differently.
All of this begs the question, What does it really mean to be "elderly"? The internet abounds with stories (and pictures) of elderly athletes and bodybuilders, many of whom are nothing short of astounding. Likewise, it's not uncommon to see relative youngsters who have aged far beyond their years (SMOKING, EXCESSIVE DRINKING, DRUGS, INFLAMMATION, sedentary lifestyle, etc, are a few of the common culprits). This begs yet another question; is there anything that might be done to slow the process down? That is the topic of today's post and the question we will attempt to answer.
Where there's smoke there's fire; and where there's either DYSBIOSIS or INTESTINAL HYPERPERMEABILITY (Leaky Gut), you're certain to find the other. Five years ago the Journals of Gastroenterolgy Series published a study showing this relationship. "Aging significantly increases the vulnerability to gastrointestinal (GI) disorders with approximately 35%–40% of geriatric patients reporting at least one GI complaint during routine physical examination. Specifically, advancing age was shown to correlate with an enhanced trans-epithelial permeability, indicating that there may be an age-associated decline in barrier function. Endogenous changes in cytokine production as a function of age can be caused by a number of factors including remodeling of the gut microbiome." As I will show you shortly, "barrier dysfunction" (epithelial permeability) is not confined to the Gut.
It's amazing just how much research there is tying one's MICROBIOME (the bacteria and other organisms that live in and on you) to one's overall health. Case in point, a study from the January issue of Cellular and Molecular Life Sciences (Role of Gut Microbiota in Aging-Related Health Decline: Insights From Invertebrate Models). "Studies in mammals, including humans, have reported age-related changes in microbiota dynamics. In this review, we discuss recent work using invertebrate models to provide insight into the interplay between microbiota dynamics, intestinal homeostasis during aging and life span determination. An emerging theme from these studies is that the microbiota contributes to cellular and physiological changes in the aging intestine and, in some cases, age-related shifts in microbiota dynamics can drive health decline in aged animals." There's the relationship folks, and if HOMEOSTASIS is not present, everything falls apart. Allow me to show you highlights from two recent studies that expounded on this relationship.
"Although there is a consensus that the dominant species that make up the adult microbiota remains unchanged in elderly people, it has been reported that there are significant alterations in the proportion and composition of the different taxa, leading to reduced microbiota diversity, as well as an increase of enteropathogens that may lead to chronic inflammation. Environment, diet, place of residence and biogeography are regulatory factors of the microbiota. Communication in the gut-brain-axis is regulated by many intermediaries including diverse metabolites of the microbiota. Microbial changes have been observed in several geriatric diseases, like Parkinson's and Alzheimer's." From the November 2017 issue of the Archives of Medical Research (Microbiota and Aging: A Review and Commentary)
"Significant changes in microbiota composition in older subjects have been reported in relation to diet, drug use and the settings where the older subjects are living, that is, in community nursing homes or in a hospital. Moreover, changes in microbiota composition in the old age have been related to immunosenescence and inflammatory processes that are pathophysiological mechanisms involved in the pathways of frailty. Frailty is an age-related condition of increased vulnerability to stresses due to the impairment in multiple inter-related physiologic systems that are associated with an increased risk of adverse outcomes, such as falls, delirium, institutionalization, hospitalization and death. Preliminary data suggest that changes in microbiota composition may contribute to the variations in the biological, clinical, functional and psycho-social domains that occur in the frail older subjects." From a 2016 issue of Digestive Diseases (Gastrointestinal Microbiota and Their Contribution to Healthy Aging)
What's fascinating about these two studies is that number one; they give us a glimpse of the "UNIVERSAL CAUSE OF ALL DISEASE". Number two, these studies not only give us a glimpse into the common cause of disease, but into the COMMON "CURE" OF ALL DISEASE as well. We clearly see this phenomenon in action in last November's issue of Frontiers in Immunology (Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice)
"Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice."
This same sort of transfer has been done with OBESITY and DEPRESSION --- both of which are INFLAMMATORY DISEASES. In other words, doing a FECAL MICROBIOTA TRANSPLANT from old mice into young mice that had been genetically raised without a microbiome, caused the young mice to appear old when numerous tests were run four weeks later. Oh, and as you can see from the word "leakage," we know that a Leaky Gut was one of the factors that was observed. Let's look at some more studies attesting to this relationship.
- INSTITUTIONS CREATE ABNORMAL MICROBIOMES: Although studies we've already discussed today mentioned it, we repeatedly see that life in institutions (nursing homes / hospitals) is rough on a microbiome. HERE is the reason why, and it has to do with the medical community's poor understanding of the HYGIENE HYPOTHESIS. January's Science Reports (Composition of Salivary Microbiota in Elderly Subjects) showed that "Frailty is gaining attention worldwide with the aging of society. We speculated that the composition of the oral microbiota is associated with general frailty, as well as a relationship between gut microbiota and general health condition. In the present study, we investigated the salivary microbiota composition in samples from healthy and frail elderly individuals. We found a significant difference in diversity between elderly individuals living in a nursing home and healthy control subjects, as well as in the microbiota composition."
- CANCER CREATES ABNORMAL MICROBIOMES: In 2014, Annual Reviews in Physiology said this about the relationship between aging and cancer in a study called Aging, Cellular Senescence, and Cancer. "For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer." We already know that aging is related to microbiome, but what about microbiome and CANCER? February's issue of Gut had something to say about this in a study called Gastric Microbial Community Profiling Reveals a Dysbiotic Cancer-Associated Microbiota. After discussing the fact that gastritis (stomach inflammation) is caused by H. PYLORI, which causes both low stomach acid and stomach cancer (see link), they looked at the microbiomes of individuals who came down with stomach cancer but were not infected with Heliobacter. "Dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis."
- WHAT HAPPENS WHEN BACTERIA GET IN PLACES THEY SHOULDN'T BE? When people's epithelial barrier system fails (something that we've already shown is more common in the elderly than in the young), they end up with THE LEAKIES (Leaky Gut, Leaky Brain, Leaky Lung, Leaky Nerve, Leaky Cord). This means they wind up with "stuff" (including pathological microorganisms) in places "stuff" should not be. And this doesn't even begin to touch on SIBO. Last month's issue of Science (Translocation of a Gut Pathobiont Drives Autoimmunity in Mice and Humans) revealed that there are, "multiple associations between the microbiota and immune diseases," specifically mentioning "autoimmunity". These authors went on to discuss "translocation of a gut pathobiont to the liver and other systemic tissues triggers autoimmune responses....." Yet another form of DYSBIOSIS that the elderly are increasingly prone to. Speaking of dysbiosis.....
- SUGAR DRIVES DYSBIOSIS: If you've spent any amount of time on my site you've heard me say that even thought ANTIBIOTICS and NON-ANTIBIOTIC MEDICATIONS are the chief causes of dysbiosis, the problem is driven by sugar (HERE). The same issue of Science seen in the last bullet point carried a study that proved it; Hyperglycemia Drives Intestinal Barrier Dysfunction and Risk for Enteric Infection. "Metabolic syndrome, leaky guts, and infection: Metabolic syndrome often accompanies obesity and hyperglycemia and is associated with a breakdown in the integrity of the intestinal barrier and increased risk of systemic infection. Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia... restores barrier function and bacterial containment." According to a study in February's issue of Molecular Nutrition and Food Research (Intake of Fish Oil Specifically Modulates Colonic Muc2 Expression in Middle-Aged Rats by Suppressing the Glycosylation Process), "Dietary fats have been shown to affect gut microbiota composition and aging gene expression of middle-aged rats at a normal dose." We know how important DIETARY FATS in general are on this process but what about specific fats like FISH OIL? "Intake of fish oil at a normal dose may involve the suppression of glycosylation processes." Once you understand how serious various forms of GLYCATION are, this study will begin to take on a new importance.
- GLUTEN DRIVES THIS MESS AS WELL: I showed you at the beginning of THIS POST that zonulin is the only known modulator of the "tight junctions" that can become 'leaky'. Why did the discovery of zonulin change the way we should view inflammation, autoimmune diseases, cancer, and almost every disease you care to mention? Wikipedia puts it this way; "Gliadin (a glycoprotein present in wheat and a component of gluten) activates zonulin irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability." It's why people with chronic illness or family history of chronic illness should never consume GLUTEN or MODERN GRAINS. Last September, the Journal of the American Medical Directors Association published a study that said it all via its title; Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging. "Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty." Not surprisingly, dysbiosis was also discussed. Then, a study from last month's issue of BMC Geriatrics (Are Self-Reported Gastrointestinal Symptoms Among Older Adults Associated with Increased Intestinal Permeability and Psychological Distress?) took things a step farther by concluding, "Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffers from higher psychological distress.... an association between GI symptoms, psychological distress and intestinal permeability." Speaking of the brain / gut connection......
- THE ELDERLY GUT AFFECTS THE ELDERLY BRAIN PART I: It's no revelation that Gut function is intimately linked to brain function (HERE). In studies released earlier this year, the Journal of Lifestyle Medicine brought us Influence of Altered Gut Microbiota Composition on Aging and Aging-Related Diseases, which stated "The microbiota of the human GI tract includes colonized microbes and their genes, proteins, and metabolites. Many researchers have reported on gut microbiota-related adverse events from development to senescence, including developmental defects, metabolic diseases, and neuro-degenerative diseases. Additionally, dysbiosis in the gut has been associated with inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes... to name a few. Composition of the microbiota changes during aging. Gram-negative bacteria increase in number during aging and secrete lipopolysaccharide, which acts as an endotoxin and induces inflammation in the human gut. The gut microbiota also affects various signaling pathways, such as inflammation and oncogenesis, as well as brain function in the hippocampus related to memory and anxiety." Later that month, Experimental Biology & Medicine (Gut Reactions: How the Blood-Brain Barrier Connects the Microbiome and the Brain) concluded, "A growing body of evidence indicates that the microbiome interacts with the central nervous system (CNS) and can regulate many of its functions. One mechanism for this interaction is at the level of the blood-brain barriers (BBBs). Bacteria can directly release factors into the systemic circulation or can translocate into blood. Once in the blood, the microbiome and its factors can alter peripheral immune cells to promote interactions with the BBB and ultimately with other elements of the neurovascular unit. Bacteria and their factors or cytokines and other immune-active substances released from peripheral sites under the influence of the microbiome can cross the BBB, alter BBB integrity, change BBB transport rates, or induce release of neuroimmune substances from the barrier cells. Metabolic products produced by the microbiome can cross the BBB to affect brain function. Through these and other mechanisms, microbiome-BBB interactions can influence the course of diseases as illustrated by multiple sclerosis." A study from February's Oncotarget (Aging-Related Dysregulation in Enteric Dopamine and Angiotensin System Interactions: Implications for Gastrointestinal Dysfunction in the Elderly) discussed the relationship of various neurotransmitters (SEROTONIN IS THE BIGGIE) to Gut function. "Aged rats showed a marked decrease in colonic dopamine D2 receptor expression, together with an increase in... levels of inflammatory and oxidative markers. Aged rats also showed increased levels of colonic dopamine and noradrenalin, and a marked decrease in acetylcholine and serotonin levels. The present observations contribute to explain an aging-related pro-inflammatory state and dysregulation in gastrointestinal function"
- THE ELDERLY GUT AFFECTS THE ELDERLY BRAIN PART II (ALZHEIMER'S): Although I have written extensively about both ALZHEIMER'S and PARKINSON'S in the past, there are numerous studies showing the link between diseases of age and the aging Gut. A study from 33 researchers from around the world (Microbes and Alzheimer's Disease) was published in the June 2016 issue of the Journal of Alzheimer's Disease, which, after concluding that this relationship is being overlooked by much of mainstream science, stated, "We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus, Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD. Fungal infection of AD brain has also been described, as well as abnormal microbiota in AD patient blood." There's a little bit of everything here, including the Leakies. Just last October Scientific Reports (Gut Microbiome Alterations in Alzheimer’s Disease) concluded that "Alzheimer’s disease (AD) is the most common form of dementia. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition... Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals."
- OLD FOLKS ARE MORE LIKELY TO HAVE TROUBLE SLEEPING & THINKING --- AND IT'S AFFECTED BY ONE'S MICROBIOME: With everything we know about the microbiome so far, why should it surprise us that it's linked to cognitive impairment and inability to sleep? The October 2017 issue of Sleep Medicine (A Preliminary Examination of Gut Microbiota, Sleep, and Cognitive Flexibility in Healthy Older Adults) stated, "Inadequate sleep increases the risk for age-related cognitive decline and recent work suggests a possible role of the gut microbiota in this phenomenon. Partial sleep deprivation alters the human gut microbiome, and its composition is associated with cognitive flexibility in animal models. Given these findings, we examined the possible relationship among the gut microbiome, sleep quality, and cognitive flexibility in a sample of healthy older adults." Might I suggest that you avoid SLEEPING PILLS. By the way, 90% of your body's serotonin is made in the Gut, and the sleep hormone melatonin, is made from serotonin.
- DRUGS DESTROY YOUR BUGS: It's not news that ANTIBIOTICS destroy microbiomes. What is news to many people is that on some level, all drugs act as antibiotics (HERE). Case in point, a study from last September's issue of Scientific Reports called Gut Microbiota Composition is Associated with Polypharmacy in Elderly Hospitalized Patients stated, "The number of drugs was associated with the average relative abundance of 15 taxa. The drug classes exhibiting the strongest association with single taxa abundance were proton pump inhibitors, antidepressants and antipsychotics. In aging, polypharmacy may thus represent a determinant of gut microbiota composition, with detrimental clinical consequences." Curious to read more about PPI'S, ANTIDEPRESSANTS, or other ANTIPSYCHOTICS, just follow the links. Another study from the same issue of the same journal (Antibiotic-Induced Perturbations in Microbial Diversity During Post-Natal Development Alters Amyloid Pathology in an Aged Murine Model of Alzheimer's Disease) dealt with the same topic. Honestly, there were so many studies I could have written a book.
- CHOLESTEROL, STATINS, AND THE AGING GUT: No group is a bigger target for the giant CHOLESTEROL SCARE than the elderly. The June 2016 issue of Lipidology (Gut Microbiome and Lipid Metabolism: From Associations to Mechanisms) stated, "The gut microbiome has now been convincingly linked to human metabolic health... Recent population-based association studies have shown that the gut microbiota composition can explain a substantial proportion of the interindividual variation in blood triglycerides and HDL-cholesterol level and predict metabolic response to diet and drug. Faecal transplantation has suggested that this is a causal effect of microbiome on host metabolism..." The September 2017 issue of the Annals of Agricultural and Environmental Medicine (Gut Microbiome as a Biomarker of Cardiometabolic Disorders) showed that certain Gut bacteria are associated with high cholesterol levels, while others were associated with the opposite. "Cardiovascular diseases are the leading cause of death in Europe and worldwide. One of the most important risk factors for atherosclerosis are lipid metabolism disorders, in particular hypercholesterolemia. The study showed that intestinal microbiome is likely to play a role in the pathogenesis of atherosclerosis through its role in lipid metabolism." The point was that risk factors could easily be determined via stool sample --- something blood has not thus far been able to do. For those of you taking a statin (or contemplating taking a statin), I would urge you to at least thumb THESE POSTS.
SOLUTIONS FOR THE AGING GUT
- EXERCISE AIDS GUT HEALTH: Last October's issue of the Journals of Gerentology (Impact of Age-Related Mitochondrial Dysfunction and Exercise on Intestinal Microbiota Composition) concluded, "Mitochondrial dysfunction is prevalent in the ageing gastrointestinal tract... Exercise did increase gut microbiota diversity.... Mitochondrial dysfunction is associated with changes in the gut microbiota. Endurance exercise moderated some of these changes, establishing that environmental factors can influence gut microbiota despite mitochondrial dysfunction." Back in 2011, Holistic Nursing Practice published a cool study called Intestinal Permeability, Moderate Exercise, and Older Adult Health that stated in its abstract, "inflammation leading to intestinal permeability (a leaky gut) may be responsible for numerous physical and mental abnormalities and associated functional decline. This may be especially true for elderly people, particularly involving the development of autoimmune disorders. In this regard, engagement in appropriate moderate exercise/physical activity can produce an anti-inflammatory effect and may have a powerful role to play as part of a holistic treatment for this potential problem. This is important information for nurses who are interested in integrative and nonpharmacologic care." Just remember that HARDCORE CARDIO can actually cause a leaky gut. Truthfully, I could have included numerous other studies here.
- CAN THE ELDERLY GUT BE MODULATED BY DIET? While this is simple to answer using old fashioned common sense, let me hit you with two six year old studies. Back in the summer of 2012, twenty six scientists, physicians and researchers from the Department of Microbiology at the University College Cork in Ireland published a study in Nature (Gut Microbiota Composition Correlates with Diet and Health in the Elderly) that showed diet matters in matters of Gut Health. "Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing." One month later, Nature Reviews: Gastroenterology & Hepatology (Gut Microbiota: Dietary and Social Modulation of Gut Microbiota in the Elderly) concluded almost the same thing when they stated, "Analysis suggests that age-associated stability of the intestinal ecosystem is strongly influenced by an individual's social and dietary status. The process of immunosenescence might serve as a causal link to explain the association between a perturbed distal gut microbiota and frailty in the elderly."
What we've seen so far is that diet and exercise play a huge part in Gut Health of the elderly. This means two things. Firstly, it means that you can play an active part in your own aging process. Secondly, it means that it's not something that someone else can do for you. In fact, we've seen today that standard medical treatment is a significant destroyer of Gut Health. In other words, Gut Health is one of those situations where LAWYERS, GUNS & MONEY aren't going to help you much. You're going to have to knuckle down and do it yourself. What might help? Probiotics.
While I am certainly a fan of probiotics, be aware that they are not without potential issues of their own. As I said HERE a number of years ago, probiotics don't come close to approximating a healthy microbiome, not to mention they come with a potential array of largely UNDERREPORTED SIDE EFFECTS. While most aren't terribly serious, you can take a look at the May 2015 issue of Clinical Infectious Diseases (Risk and Safety of Probiotics) to see what I'm talking about. A great example of this phenomenon comes from last month's issue of Probiotics and Antimicrobial Proteins (Gut Microbiota Alteration After Long-Term Consumption of Probiotics in the Elderly), which, while it could be classified as a pro-probiotic study, concluded that "The microbiota profile changes with aging... The loss of microbiota diversity and the alterations in the optimal composition and quantity of beneficial microbes are believed to increase the risk of many diseases. High-dose intake of probiotics resulted in lower microbial richness." Looking at the microbiome's big picture is part of what makes FMT so appealing for people who are seriously and chronically ill.
- PROBIOTICS AND THE ELDERLY: It's not news that antibiotics destroy microbiomes, while probiotics are the most commonly used tool for helping restore them. December's issue of Current Pharmaceutical Designs (Antibiotics Associated Disorders and Postbiotics Induced Rescue in Gut Health) concluded that "Antibiotics directly affect the gut microbiota that consequently alter the basic biological processes, and imposes severe consequences in population falling under different age groups." The gist of the study was trying to find which bacterial combinations were most helpful as a probiotic. A 2015 issue of Frontiers in Microbiology (Geriatric Respondents and Non-Respondents to Probiotic Intervention Can be Differentiated by Inherent Gut Microbiome Composition) "identified potential microbial biomarkers and taxonomic patterns that correlate with a positive response to probiotic intervention in geriatric volunteers." When looking specifically at what PREBIOTICS did for the elderly (Effect of a Prebiotic Formulation on Frailty Syndrome: A Randomized, Double-Blind Clinical Trial), a 2016 issue of the International Journal of Molecular Science concluded that, "prebiotic administration compared with placebo significantly improved two frailty criteria; exhaustion and handgrip strength." Although I will not go into them all, suffice it to say that while I found a number of studies concluding that probiotics were beneficial for the elderly, there were likewise a number of studies showing they were a wash --- typical of probiotic research.
If you are looking to slow down the metabolism of aging, while hopefully getting healthier in the process, the links in today's post provide a good starting point. I put it all together for you in a generic protocol for improving physiology and Gut Health that you can find HERE. And don't forget that the easiest way to reach those you love and care about most with the free information on our site is by liking, sharing, or following on FACEBOOK.