Humans owe a great deal to the wealth of microorganisms that reside within and on their bodies. In fact, these microorganisms outnumber our own cells and if counting total number of genes, resident microbial genes equal human genes. Thus, they are ever with us and in great numbers. Their contribution to our health and aging is just being defined. Our present understanding of the relation between aging and microorganisms, mostly bacteria, will be discussed in this blog.
Orientation
The 100 trillion microorganisms that share space with us are called the microbiota. Most of them reside in our gastrointestinal (GI) tract from the esophagus to the colon but some are located on the skin and in the urogenital tract. The GI microbiota (focus of the blog) are comprised mainly but not solely of bacteria. Other microorganisms e.g. fungi, viruses, protozoan and archaea (bacteria-like organisms) are also present but unlike the bacteria, little is known about their contribution to our health.
In the newborn, the GI tract is colonized by maternal microorganisms in several ways: before birth in utero, and during vaginal delivery or if cesarean delivery, from environmental sources. Breast milk adds additional microorganisms to the GI tract. Up to 3 years of age the microbiota is modest in size and function. Thereafter, the microbiota is more firmly established and remains fairly stable throughout adulthood. The primary, but not the only determinant of the diversity and quality of the microbiota, is the diet. As one ages into the 70s and beyond, the microbiota becomes less robust for reasons, as yet, not adequately defined.
Exceptional and Abundant Contributions of the GI Microbiota.
Our understanding of the GI bacterial microbiota has accelerated due to technological advances in genetics and molecular biology. These techniques consist of high throughput DNA analysis of multiple communities of bacteria (metagenomices) and the products they produce (metabolomics).
Beneficial bacteria contribute to our health by fulfilling the following functions:
a) Mediate and restrain inflammatory processes, energy expenditure, fat deposition and satiety (feeling full);
b) Influence numerous local activities: GI motility (movement of food via GI muscle contraction); level of neurotransmitters, serotonin, dopamine and gamma-amino-butyric acid; aid in the maturation of the immune system; facilitate GI mucus production and replacement of defective cells to keep the GI lining intact;
c) Suppress “bad” bacteria such as Clostridioides difficile and Salmonella;
d) Produce several vitamins (B and K vitamins)
Microbiota contribute impressively to our health through these various functions. It is evident that loss of these functions creates a vulnerability to disease.
Composition of the Microbiota
Microbiota bacteria belong to one of four phyla: Bacteroidetes, Actinobacteria, Firmicutes and Proteobacteria. Key points on each phyla are:
Bacteroidetes comprise 25% of the assessed bacteria and are generally beneficial. They adapt to available nutrients, expel bacterial toxins and work effectively with the immune system.
Actinobacteria include diverse members but one genus, the Bifidobacteria are stars. They produce B-vitamins and folic acid, reduce liver toxins, act as immuno-regulators, lower cholesterol and triglycerides and suppress pathogens.
Firmicutes function to metabolize carbohydrates and convert them into short chain fatty acids which are necessary for protection of the lining of the GI tract and exert anti-inflammatory actions. However, some members of phyla when found in high concentrations, create a vulnerability to GI disorders and diseases.
Proteobacteria often represent a problem since they contains some well known pathogens e.g. Salmonella, and some strains of E. coli.
Ideally, an optimal microbiota consists of an abundance of Bacteroidetes, Bifidobacteria and Firmicutes and low levels of Proteobacteria.
Factors That Shape the Microbiota: Diet and Aging
Diet:
Many factors alter the overall makeup of the microbiota and contribute to the variability that exists from one individual to the next. However, diet is of prime importance in influencing the microbiota composition. In particular, a plant-based diet, high in fruits, vegetable and fiber establish a microbiota with an abundance of diverse beneficial bacteria. Previous blogs (Insight 10, Insight 11) give examples of the components of a plant-based diets.
Classic Study
A classic study compared the microbiota of African children to that of European children. The former consume an agrarian diet high in fruits, vegetables, fiber and low in protein while European children consume a Western diet high in fats and low in fiber. The microbiota of these two groups differed significantly. Compared to the microbiota of the European children, the microbiota of African children exhibited considerable more bacterial diversity and higher amounts of bacteria that digest carbohydrate, many of which did not exist in the microbiota of European children. They also exhibited reduced amounts of pathogens such as Shigella and Escherichia and greater abundances of short chain fatty acids produced by the microbiota and essential for optimal gut health.
Additional Dietary Studies
Many controlled dietary studies, albeit limited (small number of volunteers and of short duration) in adults support these early findings. In 2020, Ghosh et al., reported the results of a yearlong clinical trial of over 600 individuals (65-79 years of age) across 5 countries eating a customized Mediterranean diet. This study assessed the microbiota, markers of inflammation, frailty and cognitive function at baseline and after one year of consumption of the Mediterranean Diet. This trial showed that adherence to the Mediterranean Diet produced an enrichment in bacterial groups that were associated with reduced inflammatory markers, reduced frailty and higher cognitive function. Clearly, long term dietary patterns are effective in establishing changes associated with optimal health.
Aging:
As evidenced by the results of the aforementioned clinical trial, dietary patterns greatly influence the microbiota after the 7th decade. Unfortunately, compared to younger individuals, the microbiota of many elderly exhibit reduced bacterial diversity. This loss of diversity has been related, in part, to changes in dietary selections influenced by age-related changes in dentition (teeth), smell and taste, and medication use. The microbiota of elderly in long term care facilities is especially deficient in beneficial bacteria and even lack the ability to recover from antibiotic therapy as is generally the case for community dwelling elderly.
Whether a loss of diversity in the microbiota contributes to age-associated conditions such as diabetes, cardiovascular disease, cancers and cognitive impairment is the focus of a plethora of current studies. As with Ghosh et al., the data suggest an association between the microbiota composition and disease states. Whether this is just a statistical association or a causal effect is unknown at present.
Strategies to Alter the Gut Microbiota
There are several potential strategies to optimize the microbiota. Based on the aforementioned discussion, it seems reasonable for one to attempt to achieve the greatest diversity in bacterial phyla. This provides the benefits of the many unique bacterial functions e.g. vitamin and short chain fatty acid production, enhanced immune function and suppression of pathogenic bacteria. Another goal is to avoid GI disorders such as any number of inflammatory bowel diseases.
Possible Strategies Are:
a) Diet
As indicated above, diet exerts a significant influence on the microbiota. Since most individuals in the USA do not consume a Mediterranean Diet, adding select substances to the diet has received considerable investigative attention. This necessitates the addition of prebiotics which are non-digestible oligosaccharides (NDOs, actually long chains of sugars making a type of carbohydrate), and soluble fermentable fibers to the diet. Plants, such as soybeans, legumes, onions, Jerusalem artichokes, and chicory are NDOs and soluble fermentable fibers include foods such as sauerkraut or kimchi. At present, the effectiveness of prebiotics is equivocal with some trials showing microbiota improvement and others not.
b) Probiotics
Probiotics, defined by the numerous health and food institutes (e.g. Health Canada, the World Gastroenterology Organization, the European Food Safety Authority, Institute of Food Technologists) are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. These live microorganisms, generally include strains of Lactobacilli, Bifidobacteria and Saccharomycetes. Currently, some brands of yogurt, fermented foods (e.g. sauerkraut) and dietary supplements contain probiotics. Despite extensive marketing and some positive clinical trial results, the FDA has not as yet given approval for probiotics.
c) Fecal Microbiota Transplants
This is transfer of fecal material from one person to another. Approved by FDA, this is an effective therapy for Clostridioides difficile (C. difficile) infection and inflammatory bowel diseases.
Summary
An enormous entourage of diverse bacteria inhabit our GI tract. Most are beneficial, assisting us in numerous ways. Scientists are keen to understand in more detail, how these bacterial colonies keep us healthy, suppress pathogens and possibly contribute to our longevity. Future studies will define the relation between aging and the microbiota. Specifically, future studies will determine whether the aging GI tract adversely harms the microbiota and whether lack of maintenance of the microbiota by poor life style choices causes GI aging and disease. It is essential to have clear answers to both of these issues.
A PDF of references for this blog is available on request.