The Microbiome in Elderly Ages

Evangelia Michail Michailidou*

1Intensive Medicine Department, Hippokration General Hospital, Greece
2Senior Student in the Department of Business Administration, University of Macedonia, Greece
3Masters Degrees, International Medicine-Health Crisis Management, Greece
4Member of Health Response team to Crisis Situations of G.H.T. Hippokration, Greece

Published Date: 24/11/2020

*Corresponding author: Evangelia Michail Michailidou, Intensive Medicine Department, Hippokration General Hospital, Senior Student in the Department of Business Administration, University of Macedonia, Masters Degrees, International Medicine-Health Crisis Management, Member of Health Response team to Crisis Situations of G.H.T. Hippokration, Greece

DOI: 10.51931/OAJCS.2020.01.000012


The microbiome

The balance of health and disease (acute or chronic) seems to be much more complex than simple induction: germ - infection - treatment - cure. The balance of health and disease seems to depend predominantly on the microbiome. A huge number of different species and groups that complement each other, interact with each other and with the host cells, contributing to any normal or pathological process of daily life from which they may be affected. As the set of human genes is called a "genome", a microbiome is the sum of the genes of all the germs in the host. It consists of about 100 trillion microbial cells, with about 8,000,000 genes (about 20,000-30,000 in the human genome). While increasing life expectancy represents a social and medical achievement, health care costs associated with recurrent illnesses and disability, which often occur in the elderly, are a financial burden and a viability challenge for the current social structure of society. The elderly population often suffers from a defect in several biological functions associated with significant changes in the intestinal microflora. The big question is whether systemic diseases are the result of a specific microbiome. Intestinal microbiome is the name given today to the entire microbial population living in the gastrointestinal tract. The human gut microbiome contains tens of trillions of microorganisms, including at least 1,000 different species of known bacteria with more than 3 million genes (150 times more than human genes). The intestinal microbiome weighs a total of up to about 2 kg. One-third of the intestinal microbiome is common to most people, while two-thirds is specific for each person [1-7].

Some of its functions are:

1. Helps the body digest certain foods that the stomach and small intestine cannot digest

2. Helps in the production of certain vitamins (B and K)

3. Defends against attacks by other pathogenic microorganisms, maintaining the smooth functioning of the intestinal mucosa and creating an advanced line of defense

4. Plays an important role in the regulation and function of many parameters of the immune system. A healthy and balanced intestinal microbiome is the key to ensuring the proper functioning of the digestive system.

Gastrointestinal and immune system

The gastrointestinal tract is obviously affected by diet. It is characteristic that homozygous twins, one of which was breastfeeding while the other was feeding on milk powder, developed a completely different intestinal flora. The effect of these effects on the human body is under investigation. What is certain, however, is that the gastrointestinal system is inextricably linked to the development of our immune system and this has been made clear through a number of studies. Intestinal colonization begins immediately after birth and progresses with age. It is generally believed that in infants, from the age of 3, the intestinal microbiome stabilizes and virtually completes, but continues to develop at a slower rate throughout life, being the immediate culmination of different environmental effects. and balances. The balance of the intestinal microbiome is affected during the aging process and as a result, older people have a substantially different structured microbiome than younger adults.

While the general composition of the intestinal microbiome is similar to most healthy people, the composition of the species is highly individualized and largely determined by the environment and diet. It has traditionally been considered that a healthy diet requires an appropriate balance of energy, macronutrients and micronutrients ingredients and water. This is especially important for the elderly, who are more vulnerable to malnutrition. The nutritional needs of the elderly are not substantially different from those of younger adults with similar anthropometric-physiological characteristics and caloric expenditure. However, the effectiveness of nutrient absorption may be reduced, eg due to difficulty chewing and loss of appetite resulting in changes in the nutritional status of the elderly. The composition of the intestinal microbiome can be varied and adjusted according to the nutrients ingested, either temporarily or permanently. The intestinal microbiome can adapt to various environmental changes, or eating habits. However, in some special cases there may be a loss of balance. This condition is called dysbiosis. Dysbiosis has been linked to various health problems, such as inflammatory bowel disease, allergies and bowel disorders, obesity, diabetes and more.

There is growing evidence that dysbiosis is associated with the pathogenesis of both intestinal and extraintestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome and celiac disease, while extraintestinal disorders include other illnesses such as allergies, asthma, metabolic syndrome, cardiovascular disease and obesity. The gut of an obese elderly person has a different microbial composition than that of a person of the same age with a normal body weight. So, the microbial population and any changes that may contribute to weight gain. Recent studies - in both human and animal models, have shown that obesity is associated, among other things, with changes in the intestinal microbial flora. Studies of the effect of overweight and its fluctuations in intestinal bacterial populations have shown changes in the gastrointestinal microbiome.

Intestinal microbiome has also been found to affect insulin resistance, inflammatory processes and obesity through interactions with epithelial and endocrine cells. Even the association of obesity with intestinal flora and microbiome shows the body's reaction in these cases often leads to the occurrence of type II diabetes. The composition of the human gut microbiome and its metabolic activities are regulated as mentioned above by the diet. Host metabolism and metabolites also interact with the intestinal microbiome and diet, forming a complex network of interactions related to intestinal health. Several factors can affect the intestinal microbial flora of the elderly and not only humans, with diet being very important. Not only dietary patterns and specific foods are involved, but also food ingredients (eg fiber provides substrates for intestinal microbial metabolism) and food-related common microbes. Numerous studies have shown the beneficial effects of prebiotics and enteric probiotics. microflora. Prebiotics, acting as "food" for certain intestinal microbes, contribute to the better functioning of the microbiome. Such components are fructooligosaccharides and inulin.

Prebiotic products have similar actions to probiotics, but not to the same degree and with the same immediacy. This is because prebiotics act indirectly, substantially enhancing the concentration of probiotics. Their main difference is that prebiotics do not contain the microorganisms themselves, but components that actually nourish and help the growth and maintenance of the already existing beneficial bacteria of the intestinal flora.

New research shows even more that the quality of the food we eat shapes the gut microbiome to such an extent, influencing and influencing the chances of developing colon cancer. bacterium Fusobacteriumnucleatum in cancerous tumors, was clearly reduced when the diet was rich in fiber. One of the ways in which the quality of nutrition affects the chances of developing a disease is through the changes caused by the gut microbiome, i.e. the composition of the population of microorganisms that live in the gut. In the laboratory, we can accurately determine the levels of all Fusobacteria, as well as many other intestinal bacteria associated with the onset and progression of inflammatory diseases and cancer, and genetically detect the intestinal microbiome.

Diarrhea associated with Clostridium Difficile

difficile infection (Clostridium difficileinfection-CDI) is the most common cause of nosocomial diarrhea in hospitalized patients. The incidence, severity and mortality of CDIs have increased significantly over the last decade. These epidemiological changes in the incidence of CDI have been partly explained by the appearance of super infectious strains, such as C. difficile BI / NAP1 / 027. Infection with this strain in patients between 60 and 90 years of age is associated with an increased risk of death from CDI. The most important risk factors for the development of CDI, mortality and disease recurrence are advanced age> 65 years and exposure to antibiotics.

In addition to killing target bacteria, antibiotics (especially broad-spectrum antibiotics) also destroy beneficial bacteria, causing an imbalance in the complex community of microorganisms in our gut, and therefore the microbiome. Antibiotics do not just kill the pathogen we are targeting. They kill whole classes of microorganisms, both beneficial and harmful, both at the site of infection and throughout the body. This mass killing of microorganisms upsets the balance of the microbiome and other microorganisms come to fill the gaps created.

In most patients the infection is treated with directed antibiotic therapy against C. difficile. However, in 20% of cases the symptoms recur and further treatment is required. Treating persistent C. difficile infection is becoming increasingly difficult as new and more resistant strains emerge. The only option left to patients suffering from these resistant strains is stool transplantation. The sampling process and the selection of those that could be used in patients are particularly rigorous. Stool transplantation carries the risk of spreading and infectious diseases. With the new data linking the human microbiome to diseases such as obesity, diabetes and allergies, it is possible that faecal transport will also lead to the transmission of these diseases. When a stool sample is deemed appropriate, it is liquefied and usually administered by colonoscopy. The population of healthy donor microorganisms retains their genome and metabolic processes and thus can induce the restoration of the balance of the infected patient's microbiome.

Although the success rate of C. difficile infections with faecal transplantation exceeds 90%, the application of the method is still rare, probably due to its specificity. The strict rules governing fecal transplants make their use difficult, as is the invasive nature of the method, in relation to antibiotics. In order to make fecal transplants more attractive, their invasive nature is modified and medication is suggested. In recent years, it has been explored whether transplants could be used to treat other common microbial-related conditions, including obesity, type II diabetes and allergies. There are also banks that store healthy stools for possible future use as is the case with stem cell banks. In particular, it should be possible to isolate a mixture of faeces of specified bacterial species and / or design synthetic mixtures that could be administered to correct intestinal discomfort, thus avoiding the risk of transmitting potentially harmful microorganisms from donors to recipients. Nevertheless, according to the international literature, the elderly age of patients (> 65 years) is presented as the main risk factor for the main failure of this treatment and the early recurrence of the disease. Finally, it is important that no cost-effectiveness studies of this method have been performed.

Microbiome and Neurodegenerative Disorders in the Elderly Ages

Elderly age is the leading risk factor for developing neurodegenerative disorders, including Alzheimer's disease (AD). According to the international literature, reduced brain metabolism and vascular dysfunction occur decades before the onset of cognitive impairment, and these reductions are largely related to the chronic inflammation that develops in brain cells over time. Interestingly, recent findings suggest that the gut microflora may also play a critical role in shaping the immune response in the brain via the brain-gut axis.

Brain-Bowel Axis

This relationship has been studied primarily in animal models from which the intestinal microflora has been removed. More specifically, the intestinal microbiome directly affects the process of synaptogenesis, the development of the dopaminergic system, the production of neurotransmitters (e.g. serotonin) and sometimes modifies the permeability of the blood-brain barrier. At the same time, products of the gut microbes (short-chain fatty acids, lipopolysaccharides) can enter the function of specific areas of the brain. On the other hand, the CNS through the hypothalamic-pituitary-adrenal axis but also through the autonomic nervous system causes changes in a number of parameters of the gastrointestinal tract, such as intestinal permeability, gastrointestinal motility and secretory activity. These changes, as expected, in turn modify the composition of the intestinal microflora.

Intestinal Microflora and Parkinson's Disease

Patient-control studies have shown that there are significant differences in the composition of the intestinal microbiome between diseased and healthy individuals. In particular, patients have reduced concentrations in the feces of Bacteroidetes, Prevotellaceae, as well as short-chain fatty acids, while, on the contrary, the concentration of Enterobacteriaceae is increased. In fact, the relative "abundance" of Enterobacteriaceae shows a positive correlation with the severity of certain symptoms of the disease (eg position instability, gait disorders). In addition, concentrations of bacteria with potentially anti-inflammatory properties (bacteria of the genus Blautia, Coprococcus and Roseburia) are elevated in healthy controls. It is worth noting that the changes described above in the intestinal microbiome are evident mainly in faecal samples rather than samples taken by sigmoid endoscopy. However, it should be noted that significant variability is also observed from person to person. An additional indicator of microbial dysbiosis, the indican concentration in urine, has been found to be higher in Parkinson's patients compared with healthy individuals.

At the therapeutic level, the use of probiotics and especially probiotics containing Lactobacilluscasei seems to improve disease parameters associated with emotional disorders, while the only clinical trial currently concerns the effect of probiotics on constipation where beneficial results have been reported. Finally, data in the literature show that changes in the intestinal microbiome are also observed in patients with lateral myotrophic sclerosis. However, the data on this issue is still scarce.

Multiple Sclerosis

Changes in the composition of the intestinal microbiome are also evident in elderly patients with multiple sclerosis (MS), as evidenced by 16S rDNA analysis of faecal samples. In total, decreased concentrations have been recorded in 21 microbial species in the colon of patients with MS. A typical example is the reduction in the number of Clostridia and Bacteroidetes. In fact, there is an association between specific changes or specific strains of the microbiome with immunological markers. In particular, a negative association of the sex of Bacteroidetes with Th17 lymphocytes, which produce IL-17 with pro-inflammatory properties, has been reported.

In addition, reduction of Clostridia and B. fragilis results in insufficient induction of CD39-bearing T-lymphocytes and exhibits immunosuppressive-immunoregulatory activity. On the other hand, it is worth noting that a similar pattern of intestinal dysbiosis has been observed in other autoimmune diseases (eg autoimmune hepatitis). At the same time, many researchers have suggested that these changes are related to specific clinical parameters, such as the onset of depressive symptoms in several patients. In these cases, the regulation of serotonin levels by the intestinal microbiome plays a key role. On the other hand, according to a recent study of control patients, there is an increase in Methanobrevibacter and Akkermansia in the colon of patients with MS compared to healthy patients.

Changes in the composition of the intestinal microbiome appeared to be related to the expression of genes involved in dendritic cell maturation, interferon signaling, and the NF-kB signaling pathway in these patients. Other germs that have been found in abundance in the intestines of people with MS are the genera Pseudomonas, Mycoplasma, Haemophilus, Blautia and Dorea. The composition of the intestinal microbiome, however, in this population seems to be influenced by therapeutic interventions and in particular by the administration of glatiramer acetate and vitamin D, as shown by comparisons between individuals receiving or not treatment. Also interesting is the fact that in addition to the composition of the intestinal microbiome, the permeability of the intestine in these patients is disturbed.

Microbiome and Psychiatric Diseases

There are data in the literature that support the involvement of the intestinal microflora in the occurrence of psychiatric diseases and especially schizophrenia and major depression. Studies in experimental animals with sterile. At the same time, a change in the expression of genes related to the process of myelination in the prefrontal cortex was found in these animals, an area that is known to be involved in the manifestation of several neuropsychiatric disorders. At the clinical level, patient-control studies have shown significant differences in plasma concentrations of bacterial displacement markers, i.e., movement of endogenous intestinal flora from the intestinal lumen to the mesenteric lymph nodes, between healthy individuals with schizophrenia (specifically CD14).

It is also worth noting that the coexistence of schizophrenia with manifestations of the gastrointestinal tract is common. Once again, it should be emphasized that one factor that complicates the interpretation of the results of these studies is the marked variability in the composition of the microbiome from person to person. At the therapeutic level, modification of the intestinal microbiome through probiotics or stool transplantation could be an alternative approach in the above patients. Clinical trials on the subject are currently few. Administration of L. Rhamnosus has been found to modify the levels of neurotransmitters in the CNS and help alleviate the symptoms of anxiety and depression, while the most important beneficial effects on the mental sphere of probiotics have been described in healthy volunteers.

Myalgic encephalomyelitis (or chronic fatigue syndrome) Another entity for which there is evidence associated with changes in the intestinal microbiome is myalgic encephalomyelitis (or chronic fatigue syndrome) common in the elderly. This entity does not currently have a clear etiology, although there is evidence that infectious agents in combination with immune response disorders may trigger its onset. Recent studies in the literature highlight significant changes in the composition of the intestinal microbiome - based on the analysis of fecal samples - between patients and healthy people. More specifically, increased concentrations of Enterococcus and Streptococcus strains have been recorded, while, respectively, decreased concentrations of Bifidobacteria and Firmicutes. At the same time, in these patients, increased values of bacterial displacement markers (lipopolysaccharides, soluble CD14) have been reported, as well as an overall reduced variety in the intestinal flora.


Based on the above, the intestinal microbiome seems to be involved in the pathophysiological mechanisms of several pathological, neurological and psychiatric diseases in the elderly. The most common finding of the studies conducted is the difference in the composition of the intestinal microbiome between patients and healthy individuals. However, this finding needs to be translated clinically and explored more systematically.

The variability of intestinal microflora observed under normal conditions from person to person is a methodological limitation in the majority of relevant studies. At the same time, the clinical significance of some interventions aimed at modifying the intestinal microbiome requires further studies with a larger number of patients to document the usefulness of each practice. Finally, since the microbiome is associated with diseases, it could be used diagnostically in order to be able to analyze the microbiome and its metabolites to calculate the chances of a person becoming ill and to take preventive measures.


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