The mi­crobes that con­trol your health

SCI­EN­TISTS ARE SEARCH­ING FOR THE BAC­TE­RIAL PRO­FILE OF BRI­TISH PEO­PLE’S GUTS, AS THE SUB­TLE DIF­FER­ENCES BE­TWEEN THE CON­TENTS OF OURS AND THOSE OF PEO­PLE ON OTHER CON­TI­NENTS COULD TELL US MORE ABOUT OUR HEALTH THAN OUR GENES

Focus-Science and Technology - - CONTENTS - WORDS: AMY FLEMING

Dis­cover how the bac­te­ria in your gut can in­flu­ence your phys­i­cal and men­tal health.

“THERE ARE MICRO­ORGAN­ISMS LIV­ING ALL OVER OUR BOD­IES… BUT THE CON­TROL CEN­TRE LIES IN THE GUT, WHICH SOME RE­SEARCHERS CREEP­ILY RE­FER TO AS THE SEC­OND BRAIN”

Species-wise, you prob­a­bly iden­tify as hu­man. But based on the num­ber of cells in and on your body, you are ac­tu­ally more mi­crobe, be­cause tril­lions of them call you home. Your hu­man genes are out­num­bered by mi­cro­bial genes and, as the sci­en­tists ex­plor­ing our mi­cro­bial ecosys­tems (known as our mi­cro­biomes) are dis­cov­er­ing, the armies of tiny free­loaders our bod­ies host are qui­etly con­trol­ling us. To­gether, they can gov­ern mood, ap­petite and im­mune re­sponses, as well as help­ing to di­gest and metabolise foods.

In some ways, our mi­crobes are more in­flu­en­tial in shap­ing who we are and how we feel than our genes, says Prof Tim Spec­tor, who runs a mi­cro­biome re­search unit at King’s Col­lege Lon­don called the Bri­tish Gut Project. “I can tell more about some­one’s health by get­ting a de­tailed screen of their mi­crobes than by screen­ing their genes,” he says, point­ing out that we’re 99.7 per cent ge­net­i­cally sim­i­lar, whereas “we only share about 20 or 30 per cent of our mi­crobes.”

A CEN­SUS OF YOUR GUTS

Spec­tor started The Bri­tish Gut Project in 2014 to map as many peo­ple’s mi­cro­biomes as pos­si­ble, so as to re­veal as­so­ci­a­tions be­tween our biomes and health. He had re­cently started study­ing stool sam­ples from the vast King’s Col­lege twins re­search reg­istry he’s led for 25 years, and was in­spired by mi­cro­bi­ol­o­gists in the US who had launched a crowd-funded study called Amer­i­can Gut. The shared aim of the Bri­tish and Amer­i­can Gut projects is to build vast banks of gut data by invit­ing the pub­lic to par­tic­i­pate. For a small fee, which is used to fund the work, par­tic­i­pants get to dis­cover which rare species they’re har­bour­ing, how their mi­cro­biome com­pares with oth­ers in their coun­try and, says Spec­tor, they’re work­ing on adding a “di­ver­sity score”, be­cause the more dif­fer­ent types of mi­crobes we host, the health­ier we tend to be.

The sam­ples col­lected by the Bri­tish Gut Project are sent to the Amer­i­can Gut lab­o­ra­tory in San Diego for anal­y­sis. Bri­tish Gut is, essen­tially, the Euro­pean wing of Amer­i­can Gut, which is work­ing with an ex­pand­ing net­work of re­searchers around the world, seek­ing to do the same. All the re­sult­ing data are open source and will form part of the am­bi­tious Earth Mi­cro­biome Project, a col­lab­o­ra­tive in­ter­na­tional push to char­ac­terise mi­cro­bial life on Earth.

There are micro­organ­isms such as bac­te­ria and yeasts liv­ing all over our bod­ies, from toes to nose, which is why the Bri­tish Gut Project will also ac­cept swabs taken from skin, mouths and vagi­nas. But the con­trol cen­tre lies in the gut, which some re­searchers some­what creep­ily re­fer to as the sec­ond brain. (Fi­nally there’s a sci­en­tific ba­sis for the idea of ‘gut in­stinct’.) By analysing the liv­ing con­tents of our guts via stool sam­ples, re­searchers can iden­tify geo­graph­i­cal dif­fer­ences – such as Amer­i­can mi­cro­biomes tend to be less di­verse than their Bri­tish coun­ter­parts – and links be­tween cer­tain mi­crobes and com­mon dis­eases.

Cur­rently, says Spec­tor, mi­cro­biome knowl­edge is 10 years be­hind hu­man ge­netic re­search. We’ve only scratched the sur­face in iden­ti­fy­ing all the mi­crobes, learn­ing what they do and how they work to­gether. But we have iden­ti­fied a group of mi­crobes that seem to be ben­e­fi­cial in most peo­ple. Peo­ple with di­a­betes, rheuma­toid arthri­tis, food al­ler­gies, ir­ri­ta­ble bowel syn­drome (IBS), col­i­tis and high blood pres­sure, says Spec­tor, “tend to lack th­ese ben­e­fi­cial mi­crobes that in other peo­ple are pro­tec­tive.”

There are strong links, also, be­tween men­tal health and gut health. Prof Felice

Jacka, who runs the Food and Mood Lab at Deakin Univer­sity in Aus­tralia, first estab­lished the field of nu­tri­tional psy­chi­a­try a decade ago and her re­search is in­creas­ingly turn­ing to mi­crobes. “All the fac­tors that un­der­pin de­pres­sion from a bi­o­log­i­cal point of view are un­der the reg­u­la­tion of the gut mi­cro­biome: in­flam­ma­tion, brain plas­tic­ity, im­mune ac­ti­va­tion in the brain, gene ex­pres­sion. It also af­fects the level of neu­ro­trans­mit­ters in the brain and has a very im­por­tant role in mod­u­lat­ing the stress re­sponse sys­tem,” she says.

Even the ef­fects of foods and drugs on our sys­tems (from an­tide­pres­sants to cancer chemo­ther­apy) are re­lated to the mi­crobes we have. “If you’re on cancer chemo­ther­apy,” says Spec­tor, “and you have the right type of mi­crobes, you’ll be three times as likely to sur­vive. So ev­ery­body go­ing onto cancer chemo­ther­apy should be get­ting their mi­cro­biome tested.” If it’s found that you don’t have the nec­es­sary mi­crobes, tak­ing pro­bi­otic sup­ple­ments con­tain­ing help­ful bac­te­ria and mak­ing di­etary changes, he says, may well im­prove your chance of liv­ing. “Amer­i­can cancer centres are

2 now rou­tinely screen­ing their pa­tients and of­fer­ing ad­vice,” notes Spec­tor, whereas the gut-chemo axis hasn’t reached Bri­tish doc­tors’ agen­das yet.

This is one among many ex­am­ples where tak­ing pro­bi­otic sup­ple­ments has been shown to be ef­fec­tive. “It’s look­ing like they do work for a wide va­ri­ety of con­di­tions,” says Spec­tor. “If you’ve got a child with di­ar­rhoea, giv­ing them pro­bi­otics will sig­nif­i­cantly speed up re­cov­ery time.” Jane A Foster, as­so­ciate pro­fes­sor in psy­chi­a­try and be­havioural neu­ro­sciences at Mc­Mas­ter Univer­sity in Canada, de­scribes the pro­bi­otics in­dus­try as a “flour­ish­ing land­scape” and fore­sees a time when pro­bi­otics will be in our or­ange juice and cho­co­late bars. But she warns pro­bi­otics aren’t al­ways the so­lu­tion. “The mi­cro­biome is partly driven by our own ge­net­ics and partly by en­vi­ron­men­tal fac­tors such as stress, diet, age and gen­der. All th­ese things af­fect the com­po­si­tion and they prob­a­bly also af­fect the func­tion of the bac­te­ria that are there.”

In other words, it’s not sim­ply a cause and ef­fect re­la­tion­ship be­tween the amount of good and bad bac­te­ria in your gut. “The only way bad bac­te­ria’s ef­fects are un­der­stood is when we have enough of them to con­sti­tute an in­fec­tion and we have ter­ri­ble gas­troin­testi­nal symp­toms such as vom­it­ing and di­ar­rhoea (due to E. coli or C. dif­fi­cile, for ex­am­ple),” ex­plains Spec­tor. “In terms of our gut flora, it’s not yet pos­si­ble to prove a causal role for any bac­te­ria, as it’s not un­der­stood how they all in­ter­act in the body. Many of them can’t sur­vive out­side the body so we can’t study them in ac­tion. The way sci­en­tists find out about what bac­te­ria we have is by find­ing their DNA.”

HAP­PI­NESS IS A HEALTHY GUT

There are ways that your body can warn you that your gut flora isn’t flour­ish­ing. Hav­ing IBS can be a sign, along with, says Spec­tor, “be­ing constipated, hav­ing a lim­ited diet, feel­ing bloated; on av­er­age, if you’re over­weight, un­well and have lots of al­ler­gies, you’re go­ing to have poor gut health.” For many, he says, this is the norm and it’s only when you change it and be­gin to feel bet­ter that you re­alise how bad it was. Your im­mune sys­tem im­proves and you have fewer colds and in­fec­tions.

To im­prove gut health, Spec­tor ad­vises dou­bling your fi­bre in­take – eat­ing whole foods, such as grains and beans, and plenty of fruits and veg­eta­bles. Fer­mented foods such as yo­ghurt, sauer­kraut and the na­tional pickle of Korea, kim­chi, are packed with friendly bac­te­ria. And ac­cord­ing to Spec­tor, the num­ber one

“THERE ARE WAYS THAT YOUR BODY CAN WARN YOU THAT YOUR GUT FLORA ISN’T FLOUR­ISH­ING. HAV­ING IR­RI­TA­BLE BOWEL SYN­DROME CAN BE A SIGN, ALONG WITH BE­ING CONSTIPATED”

re­sult so far from the Bri­tish Gut Project (which has had nearly 6,000 par­tic­i­pants) is that the peo­ple with the health­i­est guts con­sume the most di­verse num­ber of plants. “Whether you’re veg­e­tar­ian, a car­ni­vore, on the pa­leo diet or what­ever, if you get a range of plants on your plate – be they seeds, nuts, spices, herbs, fruits, veg­eta­bles, mush­rooms, grains – it’s the va­ri­ety that’s key.”

Peak gut health cor­re­sponds with eat­ing 30 dif­fer­ent plant foods each week, and Amer­i­can Gut re­ports that those in this group were also found to have the least an­tibi­otic-re­sis­tant bac­te­ria genes in their guts. The re­searchers won­dered whether this could be be­cause the par­tic­i­pants were eat­ing less meat and pro­cessed foods tainted with an­tibi­otics. (Un­sur­pris­ingly, they found that tak­ing a course of an­tibi­otics within the past month re­sulted in a less di­verse mi­cro­biome than in those who hadn’t taken th­ese medicines in the pre­vi­ous year.)

Spec­tor has since launched a sec­ond phase of gut re­search, called the Pre­dict Study, which looks at per­sonal re­sponses to dif­fer­ent foods and how this cor­re­sponds with the gut flora. The goal is to of­fer per­son­alised nu­tri­tional ad­vice by look­ing at your gut mi­crobes. Par­tic­i­pants in the study, in­clud­ing Spec­tor him­self, test their blood glu­cose lev­els af­ter con­sum­ing ev­ery­thing from ba­nanas to prosecco. The re­sponses, he says, vary widely, even in iden­ti­cal twins, “not be­cause of their genes but be­cause of their mi­crobes.” Fre­quent glu­cose spikes are re­lated to an in­crease in weight and di­a­betes, and Spec­tor has dis­cov­ered that th­ese oc­cur in him when he eats bread, whether it’s white or whole­meal. “If I eat pasta or rice,” he says, “I don’t get a spike, whereas other peo­ple might have the op­po­site. It’s the mi­crobes de­ter­min­ing that. So if you can find foods that sup­port your glu­cose lev­els, then you’re more likely to lose weight long term.”

This is one of the rea­sons why he be­lieves mi­crobe test­ing will end up be­com­ing rou­tine. Web-based mi­cro­biome test­ing ser­vices are al­ready around £100 he points out, “and as more peo­ple use them it’s go­ing to go down to £50. If the NHS did it, the price would be be­low £20 – the same price as a blood test and in­stantly more use­ful.”

Even­tu­ally, he says, “I could test your gut mi­crobe and say, based on our data­base of 10,000 peo­ple, whether you should be a rice per­son rather than a po­tato per­son.” One Bri­tish and Amer­i­can Gut find­ing al­ready de­fends al­co­hol in the on­go­ing sci­en­tific de­bate over whether any booze can ever be healthy. Hap­pily for mod­er­ate drinkers, those who con­sume al­co­hol once or more per week have more di­verse mi­cro­biomes than ab­stain­ers. And as the num­bers get big­ger, more de­tailed and sub­tle geo­graph­i­cal dif­fer­ences will be­come clear, along with gut sig­ni­fiers of dis­ease and the ef­fects of spe­cific di­ets.

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ABOVE: Prof Tim Spec­tor be­lieves a diet con­sist­ing of a di­verse range of plants and whole foods pro­motes a more di­verse mi­cro­biome

ABOVE: There are around 1,000 species of bac­te­ria liv­ing on your skin – seen here are a few of the species (and a red blood cell) found in a swab from some­one’s fin­ger­tip

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