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THE SINGAPORE MAGAZINE OF RESEARCH,
TECHNOLOGY AND EDUCATION
About Innovation   |   Editorial Matters
COVER STORY:
You Are What Your Bacteria Eat
The inside perspective of healthy aging: Take control of your intestines using novel science-based solutions
by Patricia Conway and Jorgen Schlundt

Introduction

here is a lot written today about diet, nutrition and health, and how we need to eat correctly to ensure good health. In addition, we need to eat in moderation and ensure adequate exercise to avoid otherwise serious consequences. World Health Organization (WHO) estimates that non-communicable diseases, referred to as “life-style diseases”, kill 40 million people each year, equivalent to 70% of all deaths globally. A very significant part of these deaths can be attributed to unhealthy diets and the increasing number of obese people.1 Even more worrying, the rate of obesity (also clearly related to diet) is becoming a global problem since it is now also increasing dramatically in developing countries. There is an alarming increase in diet-related diseases, such as cardiovascular disease and diabetes, which are both related to the quantity and quality of the food we eat. In fact, there is a direct correlation between the incidence of obesity and diabetes, as well as between obesity and cardio-vascular diseases.2 It has been shown that consumption of a Western style diet, high in fat and sugar and low in fibre, is more detrimental to health, and causes higher levels of obesity than a Mediterranean style diet rich in “good” fats, especially omega-3s and olive oil, multi-coloured fruits and vegetables, and even includes moderate wine consumption.3

But are we listening? Would it be easier if we understood why we need the recommended foods? This article is directed towards helping to understand why we need the foods that are recommended, by looking at what is actually happening inside us, in the intestine. Over the last 10–15 years, evidence is accumulating which shows that the amount we eat is not the only factor relevant for obesity. Researchers introduced bacteria from fat mice into slim mice and found that the slim mice then became fat, without any change in diet. Similarly, a reversal in body type was noted when they transferred bacteria from the thin mice to the fat mice, the fat mice became thin, without any change in diet.4 Recent clinical studies in humans have shown an astounding connection between the bacteria in our gut and health, and some of these investigations are now underway in Singapore. A better understanding of the important of these gut bacteria and how we can nurture them will allow us to develop means to increase the quality of life for the elderly, instead of simply focusing on life extension.

The Bacteria of the Intestine

We often hear the expression “It’s the little things that count”, and we feel good about doing small gestures for others. From the perspective of a microbiologist who studies microorganisms such as bacteria and viruses, that simple phrase can have a whole different meaning. Generally, the perception is that bacteria are bad for you, and are responsible for many diseases, but there are many good bacteria. In fact, a healthy person has trillions of bacteria in the intestine, and it is a very mixed population of bacteria that are good for us, and also some bacteria that are potentially bad if allowed to increase in numbers. The new revelation that the composition of the bacteria in the gut is directly affecting our health opens a whole new line of thinking for targeting healthy aging. Since diet and nutrition is just as important for these bacteria in the intestine as it is for the rest of the body, it is proposed that your whole body will benefit by feeding the good bacteria in your intestine.

The Role of the Intestinal Bacteria

The bacteria in our intestine contribute to our health in many ways, but can also have deleterious effects if the potentially harmful bacteria increase (Table 1). The good bacteria can prevent the growth of pathogens (bacteria that make you sick) as well as modulate the immune system and thereby protect us from infection. It is really important to appreciate that when the gut bacteria trigger the immune system in the intestine, the signals are sent all around the body and can have an effect in many organs of the body, including the respiratory tract and the skin. So if you have bad skin, you may even be able to blame it on your gut bacteria. These bacteria can help regulate the immune system throughout the body so that when needed, an inflammatory response is mounted and protects the body from an invader (typically a pathogen). It is the hormones of the immune system, called cytokines, which regulate inflammation, and thus impact on health. It is important to note that inflammation is not always related to infection caused by pathogenic bacteria, but the inflammatory response also helps our body recover after traumatic injury (which does not involve infection). Unfortunately, if the cytokine regulation fails we can get harmful inflammation throughout the body. There are many diseases which are linked to such harmful inflammation including cardiovascular disease, obesity, diabetes and arthritis.6

The gut bacteria produce vitamins and micronutrients that are essential for a healthy body. For example, some of the B-vitamins needed by the body are produced by the gut bacteria as they grow. Another compound which is produced by the bacteria is butyrate which is used by the intestinal cells as an energy source. Studies have shown a correlation between elevated levels of butyrate and a reduced risk of colon cancer.7 The most recent findings about the impact of the gut bacteria on health is the link between these bacteria and the brain.8 There is a direct interplay between substances produced by the gut bacteria, and the brain.8 There are clear links between the signals from the bacteria in the intestine and neurological conditions such as anxiety and depression — they have even managed to show increased anxiety in mice when fed human gut bacteria from anxious human volunteers. It is now understood that these neurological conditions are linked to a less favourable microbial profile in the gut.

Where are the Bacteria found in the Digestive Tract?

Firstly, it is important to understand the anatomy of the digestive tract in order to understand where the large bacterial population lives, and hence how best to feed that good bacterial population. As food is ingested, it passes via the oesophagus to the stomach where it is exposed to acids to aid in digestion of the foods. It is then passed into the small intestine which is the site of digestion and absorption of essential nutrients by the body. There are relatively small numbers of bacteria in these regions of the system. From the small intestine, food residues then pass into the large bowel (also called the colon or large intestine). This is where we find the trillions of bacteria that live in the gut, so the food available to them is what is not digested and absorbed in the small intestine. Consequently, in order to feed this huge bacterial population in the large bowel, to ensure it functions well and provides valuable health benefits, we need to include foods in our diet that reach this section of the intestine without being degraded by host enzymes. For example, dietary fibres which are poorly digested by the host enzymes in the small intestine can reach the large bowel and provide the bacteria with a substantial food supply.

The Gut Bacteria Of The Elderly

The significance of the gut bacteria for healthy aging is only now being fully realized with the use of the latest gene sequencing techniques which allow us to profile the composition of the gut bacterial community as we have not been able to do previously. This new “next generation sequencing” methodology operates by detecting the sequence of the DNA (the make up of the genes) of all the many different bacterial species in one analysis (it is estimated that we harbour more than 500 different bacterial species in the gut). This giant leap in microbiological methodology means we can show which microbial profiles are largely associated with specific medical conditions, including aging. With this information, it is now possible to develop tools for decelerating the development of bacterial profiles associated with debilitating conditions related to aging such as cognitive degeneration (e.g. dementia) and reduced functioning of the immune system (resulting in higher incidence of infectious diseases and inflammation in the elderly). In relation to brain function, it is interesting to note that the rate of creation of new brain cells (yes, we do actually continue to create new brain cells through life) can be directly related to the composition of the bacterial population in the gut. There are indications that food can be used to promote good gut health and thereby reduce inflammation and improve cognitive function in the elderly. It is established that the gut bacteria of the elderly is a less complex population compared to a healthy young adult,9 and that the immune system (maybe for that reason) is less effective, with an increased incidence of inflammation. It is alarming to note that the inflammatory cytokines linked to obesity also contribute to reduced cognitive function and with increased bodyweight there is an observed worsening of cognitive responses10 as can occur with dementia. Thus, the food we eat, and more specifically the gut bacteria we thus support, has a significant influence on many aspects of health aging.

Innovative Ways to Reverse the Changes in the Gut Bacteria in the Elderly

The demonstration of the link between the gut bacteria and the immunological and neurological deterioration opens the way to the development of diets and supplements, which promote good gut health by allowing the development of favourable microbial profiles (Fig. 1). Diets designed for the elderly focus on the protein and energy content and are supplemented with essential vitamins and minerals. An additional parameter that needs attention is feeding the good intestinal bacteria. While it has been recognized for years that a high fibre diet is good for digestive health, the understanding was that the sole function of the fibre was to promote gut motility and thereby remove undesirable toxins from the bowel. This is a valuable function for the dietary fibre, however, it can also be used as a food for the beneficial bacteria, and we now understand why this is directly related to health. The main constituents of our food are sugars (carbohydrates), proteins and lipids; fibres are typically carbohydrates. While each of these three groups include substances with beneficial effects as well as substances with negative health effects, there is mounting evidence that the bacteria that utilize the proteins that reach the large intestine are less desirable for good health and that diets rich in the dietary fibres, are almost exclusively utilized by the beneficial bacteria.11 While this can sound quite daunting to have a high fibre diet, some of the soluble fibres that promote the growth of the good bacteria are really quite palatable, and in fact even sweet tasting.

The term “prebiotic” is used to describe these complex carbohydrates (dietary fibres) that can be good for gut health by favouring the growth of the beneficial bacteria in the gut. Prebiotics should not be confused with the term “probiotic” which refers to preparations of live bacteria that have been proven to provide health benefits. The concept of probiotics dates back over a century, and there is evidence from scientifically valid clinical trials that some specific strains can improve gut health by increasing the numbers of the beneficial bacteria.12 Probiotics can be consumed directly in capsules, tablets or powders but can also be used to produce fermented foods that could create desirable microbial profiles in the large intestine. There are very many commercially available probiotic-based products, but, unfortunately not all that are marketed as probiotics have been proven to have health benefits. In many countries, there is no requirement for the food and supplements industries to provide scientific proof of the health benefits of probiotic-based products. This does certainly make it more difficult for the consumer to know which probiotic preparations can provide them with benefits. At present, the European Union permits health claims on foods with documented proof, but does not allow the term “probiotics” without proof.

Dietary Supplements which Combine Prebiotics and Probiotics are Referred to as “Synbiotics”

This term alludes to a synergism between the two components and the concept allows for effectively tailoring the selected carbohydrate supplement to be the food source for the ingested probiotic. At NAFTEC, we are developing innovative ways of designing combinations that support good microbial gut profiles to promote active and confident aging. We envisage that these NAFTEC Designer Supplements can specifically feed the good bacteria and thereby boost health and well-being.

Prebiotics as Food for the Good Bacteria

Most of the commercial prebiotics are either extracted from vegetables (e.g. inulin is prepared from the chicory root), or synthesized from simple sugars such as glucose or lactose. Many dietary fibres that are processed to reduce digestion in the small intestine can be effective prebiotics as they can reach the large bowel where they serve as food for the good bacteria. For example, resistant starch is an excellent example of a prebiotic since it is processed to ensure poor degradation in the upper tract and promotes the growth and activity of good bacteria in the large bowel.13 Resistant starch can also be formed in starchy foods as they cool after a heat treatment, with the best example being cold boiled rice.

Foods with Cognitive Benefits

Several foods have been proven to have cognitive benefits e.g. cocoa, coffee and red wine. Although the medicinal benefits of cocoa have been known for hundreds of years, more recent research has shown that chocolate has powerful brain-boosting benefits with a 50% reduced risk of cognitive decline with chocolate consumption.14 Similarly, coffee, tea and red wine have been shown to have excellent anti-oxidant and neuroprotective properties, especially in aged populations. Some traditional herbs and spices have also been linked to health benefits, including anti-inflammatory effects. Unfortunately, there are few scientifically stringent clinical studies validating many of these traditional remedies using herbs and spices. A closer examination of some of these in terms of their bioavailability and interactions with other ingredients may provide novel applications of many of these well-known ingredients.

Food Safety

Finally, but by no means of least importance, is the issue of food safety. Since the diversity of the gut microbiota of the elderly is less diverse and hence will be more prone to infection from food contaminants, added vigilance regarding food safety is required to ensure good health in the aging population. The questions that need to be addressed when considering healthy aging and food safety include the source or origin of the food and ingredients, the quality, the degree of contamination by harmful pathogens (pathogen load) and also the levels of toxins/chemicals and antimicrobial resistance carried with the food product. At NAFTEC, in collaboration with regulatory bodies both in Singapore and globally, we are developing innovative methods for monitoring foods in Singapore using latest gene sequencing technologies and biosensors, which will be linked to global data bases. It is envisaged that these technologies will provide safer food for the aging Singaporean.

In summary, many of the deleterious effects of aging can be linked to the trillions of bacteria in the large bowel, including cognitive and neurological decline, inflammation, cardiovascular disease, diabetes, obesity as well as anxiety. By modulating the diet to include complex carbohydrates, namely dietary fibres and prebiotics, benefits can be expected from an improvement of the gut bacteria. These inclusions do not need to be unpleasant, as some honeys and many fruits and vegetables are high in complex carbohydrates. It is anticipated that this innovative approach to healthy aging by targeting the intestinal bacteria and identifying dietary components and combinations (NAFTEC Designer supplements) that promote good intestinal health will hold promise for Singapore’s aging population, as well as globally.

References
  1. World Health Organization (2014) WHO Global status report on non-communicable diseases. ISBN 978 92 4 156485 4. Available at www.who.int
  2. Marinou, K, et al. (2010) Obesity and card.iovascular disease: From pathophysiology to risk stratification. Int. J. of Cardiology. 138 : 3-8.
  3. Sofi, F. et al (2010) Accruing evidence on benefits of adherence to the Mediterranean diet on health. Am. J. Clin. Nutr. 92 : 1189-96.
  4. Turnbaugh, P.J. et al (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444 : 1027-1031. | doi:10.1038/nature05414
  5. Thomas, S., et al., (2017) The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists. Cancer Research, 77(8) : 1783-1812.
  6. Rehman, T., (2012) Role of the Gut Microbiota in Age-Related Chronic Inflammation. Endocrine, Metabolic & Immune Disorders - Drug Targets, 12(4) : 361-367.
  7. Marchesi, J.R., et al., (2016) The gut microbiota and host health: a new clinical frontier. Gut, 65(2): 330-339.
  8. Foster, J.A., et al., (2016) Gut Microbiota and Brain Function: An Evolving Field in Neuroscience. International Journal of Neuropsychopharmacology, 19(5): 1-7.
  9. Claesson, M.J., et al., (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature, 488(7410) : 178-185.
  10. Walther, K et al., (2010) Structural brain differences and cognitive functioning related to body mass index in older females. Hum Brain Mapp. Jul; 31(7) : 1052-64.
  11. Colon, M.A & Bird, A.R. (2015) The impact of diet and lifestyle on gut microbiota and human health. Nutrients. Jan; 7(1) : 17–44.
  12. World Gastroenterology Organisation Global Guidelines (2017). Probiotics and prebiotics. World Gastroenterology Organisation.
  13. Wang, et al. (1999) In vitro utilization of amylopectin and high amylose maize (amylomaize) starch granules by human colonic bacteria. Applied and Environmental Microbiology 65: 4848-4854.
  14. Moreira A et al, (2016) Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline. J. Alzheimer’s disease 53(1) : 85-93.

Prof Jorgen Schlundt is the Michael Fam Chair Professor at the School of Chemical and Biomedical Engineering (SCBE) and Director of the NTU Food Technology Centre in the College of Engineering, NTU (NAFTEC). He can be contacted at jschlundt@ntu.edu.sg.

Prof Patricia Conway is a Visiting Professor at SCBE and NAFTEC, NTU. She can be contacted at pconway@ntu.edu.sg.

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