A lot to digest

Microbiologist Prof Gerald Tannock prepares to work with a ‘‘glove box’’ in his laboratory at the...
Microbiologist Prof Gerald Tannock prepares to work with a ‘‘glove box’’ in his laboratory at the University of Otago. The apparatus creates an oxygen-free environment, replicating the human colon and allowing researchers to cultivate species of bacteria as they seek to unravel the complexities and benefits of the gut’s microbiota. Photo: Gregor Richardson.
The bacteria within our gut offer great potential. So much so, that modern medicine is rethinking its relationship with the trillions of organisms that roam deep within us. Shane Gilchrist enters the matrix.

Gerald Tannock could have drawn a connection between the pair of humans sitting at a table enjoying morning tea and the bacterial activity their consumption might later promote, but he doesn’t.

Instead, the internationally respected microbiologist simply leads the way along the eighth floor of the University of Otago’s department of microbiology and immunology building, a place where various gut germs are both scrutinised and celebrated.

Unintentional it may be, but there is a symbolism to our progress: to get from reception to the office of this expert on the various inhabitants of the human gut, we must pass through a dining room.

It is estimated there are 10,000 times more bacterial cells in the human colon (also known as the large intestine or large bowel) than there are humans on Earth.

Comprising tens of trillions of micro-organisms, including more  than 3 million genes (150 times more than human genes), this colony on average weighs about 1.5kg, of which about a third is common to most people; the remainder is specific to each individual.

Although they can lead to infection should they escape from the colon, many of these organisms are essential for our health.

In fact, modern medicine is rethinking its relationship with gut bacteria, whose benefits go beyond helping the body process fibrous foods that the stomach and small intestine have not been able to digest.

Recent research has revealed the gut produces a wide range of hormones and contains many of the same neurotransmitters as the brain.

The gut wall also contains neurons that are part of a network known as the enteric nervous system.

Communicating to the brain via a "brain-gut axis", this network’s various functions include the regulation of eating.

Gut health also has implications in neurological and neuropsychiatric disorders, including multiple sclerosis, autistic spectrum disorders, and Parkinson’s disease; connections between age-related gut changes and Alzheimer’s disease have also been made; and various animal studies have shown that manipulating the gut microbiota in some way can produce behaviours related to anxiety and depression.

Prof Tannock describes the interactions that occur within the bacterial community and the links between that community, the food it is fed and the human host as a "highly interactive matrix".

He also points out that, of the estimated 10 million different kinds of microbes in nature, only 5000 have been cultivated and characterised in a laboratory.

In short, there are myriad chemical transformations yet to be investigated. And this includes those that occur within our gut.

An article in respected journal PLOS Biology last year included agreement from several experts in the field that a deeper knowledge of the relationship between the foods we consume and the properties of our gut microbial communities could "herald a new epoch of precision nutrition", possibly preventing as well as treating disease.

On average, a human has a self-regulating community of about 160 different bacteria species in the gut. Most are anaerobic (they are killed by oxygen). Yet there is a much greater variety in the collective gut of all mankind; about 1500 different species of gut bacteria are known to exist.

Which raises an obvious question: why doesn’t every human have every species?

"A huge number of bacteria can do the same job, even though they may be genetically distinct," Prof Tannock explains. ‘

"Different humans can have different compositions of microbiota ... yet the biochemical capacity of each community is pretty much the same."

The gut microbiota also offers a window into human evolution.

Our digestive systems are better designed to digest protein and fat, but not to the same extent, the plant polysaccharides and fibrous matter we ingest, Prof Tannock says.

Because we haven’t developed a way to encode enzymes to deal with all of this, we allow some bacterial genes access, providing a place in our body — the gut — where they can live happily and help the digestion of fibrous matter in a fermentation process that produces energy (and, as a byproduct, gas).

"There is an evolutionary advantage to this. At one stage it would have been important to extract energy from fibrous material. For example, in times of famine.

"Now, of course, people have plenty of calories in their diet."

In recent years, scientists have been looking at the faecal biota of hunter-gatherers, including some communities in Africa and South America, where there is a division of labour: men hunt, women forage for roots and tubers.

"The women tend to eat more of that plant material," Prof Tannock explains.

"Thus there is a difference in the microbiota within that community. Another study involved giving some people radically different foods. And under those conditions there were changes in the micro-biota.

"Clearly, if you change the fuel that is being delivered to the micro-biota, it must have an effect."

Yet herein lies potential for confusion: the microbiota in the gut has the ability to react to what it is being fed, but it is also "very stable", Prof Tannock says, using antibiotics to illustrate this point.

Notwithstanding the variances in antibiotics’ pharmacology (some don’t go anywhere near the gut), a typical 10-day course of an antibiotic could prompt some changes in the microbiota.

"But a month later it has gone back to what it was. You can’t eradicate the entire community; there is always a residuum there that will bloom again.

"There are a lot of bacterial species. There are specialists that deal with particular kinds of carbohydrates or fibre, for instance. Then there are generalist bacteria that have lots of genes and are able to switch these genes on and off depending on what is being processed."

It is an exciting time for gut microbiology, not only in a general sense, but also for Prof Tannock and his department.

He has recently completed a book on the subject, Understanding the gut microbiota, and is expecting proofs back from publisher, John Wiley and Sons, later this month.

He hopes it will be released before the end of the year.

Having researched the microbiota of the human colon for 40 years, Prof Tannock has an international reputation that might just put his book on many academic shelves: in 1996 he was appointed to a personal professorial chair at the University of Otago; in 2000, his contributions to science and technology were recognised with a Royal Society of New Zealand Silver Medal; and in 2002 he was elected a Fellow of the American Academy of Microbiology, only the second New Zealander to receive the honour.

"Hopefully, the next 10 years will see the growth of further new ways of doing microbiota science," he writes in the preface to his book.

This touches on another initiative.

The department of microbiology and immunology is preparing an application to the University of Otago to establish a "human research centre", called Microbiome Otago, involving more than 30 founding scientific and clinical researchers across a range of related disciplines and institutions, both in New Zealand and overseas.

"The application process is just starting so we will hear later in the year, but we believe it would be the flagship for human microbiome research in New Zealand.

"Microbiome research really does have to be interdisciplinary. There are so many tools that we need: you have to have clinicians, human nutritionists, biome-informatics, chemists ... I think such a centre would really boost our ability to do some good work."

Differences in the composition of the microbiota in the human colon might have been recognised a century ago, yet detailed analysis has only been possible in the past two decades, thanks largely to the development of DNA sequencing technology (what is known as the beginning of "Big Biology").

Subsequently, attention quickly turned to the microbial communities that were evident but not yet studied in depth.

This approach included breakthroughs in statistical methodology (bioinformatics) that helped the analysis of large amounts of sequencing data.

Comprising many hundreds of different kinds of microbes, the DNA of these communities could be sequenced, providing a catalogue of species types and, importantly, an indication of the metabolic capacities of communities.

This combination of approaches  helps answer two fundamental questions: "what is there?" and "what can they do?".

The subject began capturing the public’s imagination in the early 2000s when eminent American microbial expert Jeffrey Gordon published research into the role gut health played in obesity.

"Of course, once you start saying the gut biome has a role in obesity ... well, there’s a headline," Prof Tannock reflects.

"All the media picked up on that. The profile of the human microbiome now is very high. Some people think the microbiota has only been discovered in the past year.

"For much of my career — I’ve been working in this area for more than 40 — there have probably been no more than about 20 groups interested in microbiota. All of a sudden, there are hundreds of groups. From a scientist’s point of view, that’s great."

Babies and bacteria

Gerald Tannock, research professor in the University of Otago’s department of microbiology and immunology, is investigating a "medical food-like product" that might aid the nutrition of babies in special circumstances.

"For example, data worldwide shows that Caesarean-delivered babies, early in life, have a faecal microbiota that differs from babies that have been delivered vaginally."

Prof Tannock, who has been collaborating with other scientists in a project aimed at demonstrating the importance of a group of bacteria called Bifidobacterium to the early programming of our immune systems, says there is also a fascinating relationship between a mother, her milk, and the types of bacteria found in a baby.

Studies have shown that Bifidobacterium comprises up to 90% of the total bacterial mass in a breast-fed baby’s colon, a composition that suggests its importance to our gut "set-up".

In comparison, infants fed cow milk-based formula had 20% less Bifidobacterium.

"What we’ve shown so far is that immune cells do respond in different ways to different Bifidobacterial species."

Last year, the University of Otago scientist received $1 million to lead research into the development of a new food for babies during weaning.

The food will contain novel dietary fibres that better sustain energy release through the night so babies won’t wake up from hunger.

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