Human Microbiome – what is it?^[1]

A microbiome (from the Ancient Greek mikrós, meaning ‘small’, and bíos, meaning ‘life’) is the family of microorganisms that can usually be found living together in any given habitat. The term ‘human microbiome’ refers to the complete set of genes contained in the entire collection of microorganisms that live in the human body. There’s much more to humans than skin and bones: tens of trillions of microorganisms, primarily bacteria, live in the human body and constitute the ‘human microbiome’.

Microbiologists study microorganisms such as bacteria, viruses, algae, fungi, and some types of parasites. They try to understand how these organisms live, grow, and interact with their environments. The diversity of the human microbiome was first observed by Antonie van Leeuwenhoek, a Dutch businessman and scientist in the Golden Age of Dutch science and technology, the 17^th century. A largely self-taught man in science, he is commonly known as “the Father of Microbiology” and one of the first microscopists and microbiologists.^[2] Van Leeuwenhoek is best known for his pioneering work in microscopy and his contributions toward establishing microbiology as a scientific discipline. In the early 1680s, he noted a striking difference between microbes found in samples taken from the mouth versus those in faecal stools.

In 1988, Whipps and his colleagues (Lewis and Cooke)^[3], working on the ecology of rhizosphere microorganisms, provided the first definition of the term microbiome^[4]. They described the “microbiome” as a combination of the words “micro” and “biome”, naming a “characteristic microbial community” in a “reasonably well-defined habitat which has distinct physio-chemical properties” as their “theatre of activity”.

Many other microbiome definitions have been published in the last few decades. The currently most cited definition by Nobel laureate Joshua Lederberg^[5] describes microbiomes within an ecological context as a community of commensal, symbiotic, and pathogenic microorganisms within a body space or other environment. Worth reading is a paper on Researchgate by Jonathan Eisen^[6].

How Microbiome Research Started

Microbiome research originated in microbiology in the 17^th century. New techniques and equipment boosted microbiological research and caused paradigm shifts in understanding health and disease:

• The development of the first microscopes allowed the discovery of a new, unknown world and led to the identification of microorganisms.
• Infectious diseases became the earliest focus of interest and research. However, only a small proportion of microorganisms are associated with disease or pathogenicity. The overwhelming majority of microbes are essential for healthy ecosystem functioning and known for beneficial interactions with other microbes and organisms. The concept that microorganisms exist as single cells began to change as it became increasingly obvious that microbes occur within complex assemblages in which species interaction and communication are critical.

Discovery of DNA

DNA is fairly easy to understand yet hard to explain. DNA is short for Deoxyribonucleic acid, a polymer (from the Greek, it means many parts) composed of two polynucleotides chains (best to look it up on the Study.com website^[7]) that coil around each other to form a double helix carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids.

Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life. For a timeline on the discovery of DNA, please visit: https://www.dna-worldwide.com/resource/160/history-dna-timeline

The discovery of DNA, the development of sequencing technologies, PCR^[8], and cloning techniques enabled the investigation of microbial communities using cultivation-independent approaches.

Picture citation: The double helix of DNA biochemistry A section of DNA. The bases lie horizontally between the two spiralling strands^[15] (animated version). This work has been released into the public domain by its author, brian0918. This applies worldwide.

Page URL: https://upload.wikimedia.org/wikipedia/commons/0/0c/DNA_animation.gif  

More than 1000 species of microbes – what do they do?

The human gut is home to more than 1000 species of microbes that make up the human gut microbiome, the majority of which is composed of bacteria and is responsible for several benefits experienced by the host, such as protection from pathogens and enhanced nutrition.

The NHS Research Authority^[9] says:

“A shift in specific microbial communities has been associated with certain chronic illnesses such as inflammatory bowel disease and coeliac disease. Transplantation studies of microbiotas from diseased individuals to healthy individuals have shown that the microbiome can be sufficient to trigger disease. Further studies have drawn links between disease, the microbiome and host genetic variation, suggesting that the microbiome may have a heritable component. The research results will be used to establish connections between regions of the human genome and the microbiome’s composition. The results of this study can reveal fundamental human host microbe interactions that may apply to the prevention and treatment of certain diseases.”

In a healthy person, the microbes or “bugs” coexist peacefully, with the largest numbers found in the small and large intestines but also throughout the body. The microbiome is even labelled a supporting organ because it plays so many key roles in promoting the smooth daily operations of the human body.^[10]  Harvard says:

“Each person has an entirely unique network of microbiota that is originally determined by one’s DNA. A person is first exposed to microorganisms as an infant, during delivery in the birth canal and through the mother’s breast milk. Exactly which microorganisms the infant is exposed to depends solely on the species found in the mother. Later on, environmental exposures and diet can change one’s microbiome to be either beneficial to health or place one at greater risk for disease. The microbiome consists of microbes that are both helpful and potentially harmful. Most are symbiotic (where both the human body and microbiota benefit), and some, in smaller numbers, are pathogenic (promoting disease).”

Bacteria are microorganisms and come in various shapes: they can be spheres, rods, or spirals. Some bacteria are bad (called pathogenic) and will cause diseases. However, there are also good bacteria that are necessary to help our bodies function in a normal way. In our bodies, we have ten times more bacterial cells than we have human cells.^[11]  However, a recent study says that the ratio is closer to one-to-one^[12]. According to these estimates, you are likely to have 39–300 trillion bacteria living inside you – mostly in your gut.

Changing your Diet

Many factors, including the foods you eat, can impact the type of bacteria in your digestive tract.

Healthline suggests several science-based ways^[13] to improve your gut bacteria:

· Eat a diverse range of foods: A diet consisting of different food types can lead to a more diverse microbiome.

· Eat lots of vegetables, legumes, beans, and fruit: (the best sources of nutrients for a healthy microbiome). High-fibre foods that are good for gut bacteria include raspberries, artichokes, green peas, broccoli, chickpeas, lentils, beans, whole grains, bananas and apples.

· Eat fermented foods. Fermented foods have undergone fermentation, a process in which yeast or bacteria break down the sugars they contain. Some examples of fermented foods are yoghurt, kimchi, sauerkraut, kefir, kombucha tea and tempeh.

· Eat prebiotic foods: Prebiotics are foods that promote the growth of beneficial bacteria in the gut. They are mainly fibre or complex carbohydrates that human cells cannot digest. Instead, certain types of bacteria in the gut break them down and use them for fuel. Certain prebiotics have also been shown to reduce insulin, triglyceride, and cholesterol levels in people with obesity, which could be beneficial for preventing conditions like heart disease and type 2 diabetes.

· Eat whole grains: Whole grains contain lots of fibre and non-digestible carbohydrates, such as beta-glucan. These carbohydrates are not absorbed in the small intestine and instead make their way to the large intestine to promote the growth of beneficial bacteria in the gut. However, there is some research showing that gluten-containing grains — such as wheat, barley, and rye — may negatively impact gut health by increasing intestinal permeability and inflammation in some people.

· Eat a plant-based diet: Diets containing animal-based foods promote the growth of different types of intestinal bacteria than plant-based diets do. Several studies have shown that vegetarian diets may benefit the gut microbiome, which may be due to their high fibre content.

· Eat foods rich in polyphenols: Polyphenols are plant compounds with many health benefits, including reductions in blood pressure, inflammation, cholesterol levels, and oxidative stress. Examples of foods rich in polyphenols are cocoa and dark chocolate, red wine, grape skins, green tea, almonds, onions, blueberries and broccoli.

· Increase your intake of probiotics: Probiotics are live microorganisms, usually bacteria, that provide a specific health benefit when consumed. Probiotics do not permanently colonise the intestines in most cases. However, they may benefit your health by changing the overall composition of the microbiome and supporting your metabolism. Alternatively, you can consider using a probiotic supplement. However, be sure to talk with your doctor first.

Probiotics^[14]

Having the right gut bacteria has been linked to numerous health benefits^[15], including:

• weight loss
• improved digestion
• enhanced immune function
• healthier skin
• reduced risk of some diseases

Probiotics (friendly bacteria) provide health benefits when eaten or taken as supplements to help colonise your gut with good microorganisms. However, scientists often disagree on what the benefits are, as well as which strains of bacteria are responsible^[16].

Probiotics are usually live bacteria, but certain forms of yeast can also function as probiotics. Other gut microorganisms are also being studied, including viruses, fungi, archaea, and helminths^[17].

Probiotics are thought to help restore the natural balance of bacteria in your gut (including your stomach and intestines) when it has been affected by an illness or treatment.

There is some evidence that probiotics may be helpful in some cases, such as helping prevent diarrhoea when taking antibiotics and helping to ease some symptoms of irritable bowel syndrome (IBS). However, there’s little evidence to support many health claims made about them. For example, there’s no evidence to suggest that probiotics can help treat eczema. But, for most people, probiotics appear to be safe.

Issues

If you’re considering trying probiotics, there are a few issues about which you need to be aware. Probiotics are generally classed as food rather than medicine, meaning they don’t undergo the rigorous testing that medicines do. Because of the way probiotics are regulated, you can’t always be sure that:

• the product actually contains the bacteria stated on the food label
• the product contains enough bacteria to have an effect
• the bacteria can survive long enough to reach your gut

There are many different types of probiotics that may have other effects on the body, and little is known about which types are best. You may find a particular type of probiotic helps with one problem. But this does not mean it will help improve other issues or that different types of probiotics will work just as well. And there’s likely to be a huge difference between probiotics that show promise in clinical trials and the yoghurts and supplements sold in shops.

Mayo Clinic scientists have developed a mathematical index

Mayo Clinic scientists have developed a mathematical index to distinguish a healthy microbiome from a diseased one, it was announced in the press release they issued on 15^th September 2020^[18]:

‘What causes some people to develop chronic diseases such as rheumatoid arthritis, cancer and metabolic syndrome while others stay healthy? A major clue could be found in their gut microbiome — the trillions of microbes living inside the digestive system that regulate various bodily functions. To utilize the huge population of tiny organisms as a proxy for people’s well-being, Mayo Clinic researchers have developed a Gut Microbiome Health Index.

‘This index distinguishes a healthy microbiome from one that is diseased. In a new study published in the Sept. 15 issue of Nature Communications, the researchers reveal how their index, composed of a biologically-interpretable mathematical formula, can take a gut microbiome profile from a person’s stool sample to reveal the likelihood of having a disease independent of the clinical diagnosis. “This discovery advances our understanding of the composition of a healthy gut microbiome that has been long sought after,” says Jaeyun Sung, Ph.D., the corresponding author. “Our index predicts how closely a gut microbiome sample resembles healthy or unhealthy conditions.” Dr. Sung is an assistant professor of surgery, Mayo Clinic College of Medicine and Science, and researcher within the Mayo Clinic Center for Individualized Medicine Microbiome Program.’

Microbiome protects host and plays an important role in disease risk

Harvard says^[19] that the human microbiome consists of the genes of tiny organisms (bacteria, viruses, and other microbes) found in the gastrointestinal tract, primarily in the small and large intestine. The normal gut flora — another term for the microbiome — protects its human host. For the microbiome to flourish, the right balance must exist, with the healthy species dominating the less healthy.

Scientists do not fully understand how the microbiome factors into the risk of developing chronic diseases, such as heart disease, obesity, and type 2 diabetes. Many factors, including differences between individuals and individual diets, have made this a difficult area to investigate.

The Microbiome Diet^[20]

It’s no secret that the foods we eat affect our weight. Scientists are learning the food you eat can impact not just your weight but also your overall health and well-being.  

Besides helping with weight loss, friendly bacteria and a balanced microbiome have many other potential health benefits, including: 

• Promoting better sleep
• Influencing mood 
• Supporting bone development
• Producing crucial vitamins, minerals and other nutrients 
• Manufacturing natural antibiotics 
• Reducing fatigue
• Clearing acne and eczema 
• Reducing joint and muscle pain

If the levels of your gut bacteria are unbalanced, your risk of irritable bowel syndrome (IBS), infections, diabetes and heart disease is increased.

How the microbiome diet works

Gut microbes respond quickly to a change in diet. Amazingly, the lifespan of a microbe is only about 20 minutes, meaning the composition of your microbiome can be changed in next to no time simply by eating foods on which healthy bacteria thrive. 

Prebiotics (foods that feed beneficial bacteria) and probiotics (foods that contain beneficial bacteria) are the building blocks of the microbiome diet. Adding just one to three servings of these foods to your everyday diet can feed and nurture your microbiome. 

 Eat enough but not too much

The microbiome diet promotes eating enough, but not too much, and consuming mostly plant-based foods. Your body needs adequate amounts of foods to keep gut bacteria alive but not overwhelmed with nutrients, as this can lead to imbalances in the species of bacteria found in your microbiome. Eating mostly plants rather than animal products helps reduce the populations of bacteria associated with obesity. 

Alternatives to sugar^[21]

Carbohydrates may be part of a healthy diet, but doctors often advise limiting the intake of refined sugar. Instead, researchers have been interested in maintaining the sweetness of products while reducing overall sugar intake. The reasons are simple:

• People are often looking for sugar substitutes which has led to the development of low-calorie artificial sweeteners.
• Diet composition, including sugar consumption, can influence gut bacteria, which impacts overall health.
• A recent study examined the prebiotic, or bacteria-stimulating, effects of a new sweetener.
• The researchers found that the new low-calorie sweetener promoted the growth of beneficial gut bacteria.

A recent study published in the Journal of Agricultural and Food Chemistry^[22] looked at the potential prebiotic benefits of the new artificial sweetener and its sweetness level. They found the sweetener passed both the sensory testing panel and promoted the growth of helpful gut bacteria. You might want to read a separate paper (Are Sweeteners Bad for You) – email me at mpollins@onesmartplace.com for a copy if you are interested.

Conclusions

After taking advice from your GP or dietitian, you can follow the guidelines at integrisok^[23] to choose microbiome-balancing foods. Good luck. I might give it a try myself!

Sources and Further Reading

• https://www.theguardian.com/news/2018/mar/26/the-human-microbiome-why-our-microbes-could-be-key-to-our-health
• https://en.wikipedia.org/wiki/Microbiome
• https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/microbiome-and-diet/
• https://www.hsph.harvard.edu/nutritionsource/microbiome/
• https://www.health.harvard.edu/blog/diet-disease-and-the-microbiome-2021042122400
• https://www.webmd.com/digestive-disorders/ss/slideshow-microbiome-overview
• https://newsnetwork.mayoclinic.org/discussion/mayo-scientists-develop-mathematical-index-to-distinguish-healthy-microbiome-from-diseased/
• https://med.stanford.edu/news/all-news/2021/07/fermented-food-diet-increases-microbiome-diversity-lowers-inflammation https://www.hopkinsmedicine.org/health/wellness-and-prevention/5-foods-to-improve-your-digestion
• https://www.researchgate.net/publication/276101312_What_does_the_term_microbiome_mean_And_where_did_it_come_from_A_bit_of_a_surprise
• https://www.genome.gov/genetics-glossary/Bacteria
• https://www.bmj.com/content/361/bmj.k2179
• https://www.medicalnewstoday.com/articles/microbiome-diet
• Book: The Gut Microbiome: Exploring the Connection between Microbes, Diet, and Health, 31^st October 2017, by Ana Maria Moise, published by Greenwood, available at: https://www.amazon.co.uk/Gut-Microbiome-Exploring-Connection-Microbes/dp/1440842647
• Book: The Microbiome, Gut Health and Oriental Medicine: An Integrated Approach, 21st June 2022, by Lisa Lee, published by Singing Dragon, available at: https://www.amazon.co.uk/Microbiome-Gut-Health-Oriental-Medicine/dp/1787759857/
• YouTube Video: How fermented foods improve immune responses, at https://youtu.be/AH-rhycjKVk
• YouTube Video: What Role Does our Microbiome Play in a Healthy Diet?  at: https://youtu.be/-LUuqxQSaFQ

[1] Source: largely from: https://en.wikipedia.org/wiki/Microbiome

[2] Sources: (1) Chung, King-thom; Liu, Jong-kang: Pioneers in Microbiology: The Human Side of Science. (World Scientific Publishing, 2017, ISBN 978-9813202948 and (2) Scott Chimileski, Roberto Kolter. “Life at the Edge of Sight”. hup.harvard.edu. Harvard University Press.

[3]  University of Warwick (UK) professor John M. Whipps and colleagues Karen Lewis and Roderic C. Cooke

[4] Source Whipps J, Lewis K, Cooke R. Mycoparasitism and plant disease control. In: Burge M, editor. Fungi Biol Control Syst. Manchester University Press; 1988. p. 161-187.

[5] Source: Lederberg J, Mccray AT. `Ome Sweet `Omics–A genealogical treasury of words. The Scientist. 2001;15(7):8–8. See: https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00875-0

[6] Citation: Eisen, Jonathan. (2015). What does the term microbiome mean? And where did it come from? A bit of a surprise … The Winnower. 10.15200/winn.142971.16196. Source: https://www.researchgate.net/publication/276101312_What_does_the_term_microbiome_mean_And_where_did_it_come_from_A_bit_of_a_surprise

[7] At:  https://study.com/academy/lesson/polynucleotide-structure-lesson-quiz.html

[8] Explanation: The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific

DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) to a large enough amount to study in detail. Source: https://en.wikipedia.org/wiki/Polymerase_chain_reaction

[9] At: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/microbiome-and-diet/  © Crown Copyright acknowledged

[10] Source: https://www.hsph.harvard.edu/nutritionsource/microbiome/

[11] Source: https://www.genome.gov/genetics-glossary/Bacteria

[12] Ibid

[13] Source: https://www.healthline.com/nutrition/improve-gut-bacteria

[14] Sources: (1) https://www.nhs.uk/conditions/probiotics/ © Crown copyright acknowledged, and (2) https://www.healthline.com/nutrition/probiotics-101

[15] Sources: (1) Valdes, A.M.; Walter, J.; Segal, E.; Spector, T.D. Role of the gut microbiota in nutrition and health. BMJ 2018, 361, k2179. [Google Scholar] [CrossRef] [PubMed][Green Version], and (2) Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464, 59–65. [Google Scholar] [CrossRef] [PubMed][Green Version]

[16] See: https://www.tandfonline.com/doi/full/10.1080/19490976.2017.1345414

[17] Source: https://www.mdpi.com/2076-2607/8/4/483

[18] See the press release in full at: https://newsnetwork.mayoclinic.org/discussion/mayo-scientists-develop-mathematical-index-to-distinguish-healthy-microbiome-from-diseased/

[19] Source: https://www.health.harvard.edu/blog/diet-disease-and-the-microbiome-2021042122400

[20] Source: https://integrisok.com/resources/on-your-health/2020/january/how-the-microbiome-diet-can-impact-more-than-your-weight

[21] Based on article found at: https://www.medicalnewstoday.com/articles/could-a-low-calorie-sweetener-also-improve-gut-bacteria

[22] See: https://pubs.acs.org/journal/jafcau

[23] Source: https://integrisok.com/resources/on-your-health/2020/january/how-the-microbiome-diet-can-impact-more-than-your-weight