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The fu­ture’s path to a healthy mind may go via your stom­ach

To nutrition-con­scious food­ies, the mind-gut con­nec­tion is noth­ing new. But psy­chobi­otics – a grow­ing strand of neu­ro­science – is ex­plor­ing the ways that feed­ing your mi­cro­biome could hold the key to com­bat­ing men­tal ill­ness

In the dark depths of my un­der­wear drawer, behind the date-night bra and the grippy socks, sits a pack of pills. Pop­ping one with my cof­fee is as much a part of my morn­ing rou­tine as the dou­blesnooze and the Ra­dio 4 To­day pro­gramme – it is mus­cle mem­ory. They’re citalo­pram – an an­tide­pres­sant I take for anx­i­ety that, for the past few years, has made it­self known when­ever I’ve been look­ing the other way. I have no shame in the con­tents of my top drawer, but I’m be­com­ing in­creas­ingly cu­ri­ous about the re­cent raft of re­search that’s ex­plor­ing a new al­ter­na­tive – the likes of which I might find in my fridge. The lat­est fron­tier of neu­ro­science isn’t re­ally about the brain – it’s all about the gut. The gut mi­cro­biome is now thought to be just as in­flu­en­tial as our genes in de­ter­min­ing who we are, and the study of psy­chobi­otics – broadly de­fined as any in­ter­ven­tion that af­fects the brain through the trig­ger­ing of gut bac­te­ria – is grip­ping the in­ter­est of re­searchers.

‘We’ve seen this area of re­search evolve so much over the past five years, driven not only by ad­vances in tech­nol­ogy, but also strong pub­lic in­ter­est,’ says Pro­fes­sor John Cryan, chair of the De­part­ment Of Anatomy & Neu­ro­science at Univer­sity Col­lege Cork, prin­ci­pal in­ves­ti­ga­tor at the APC Mi­cro­biome In­sti­tute and co-au­thor or The Psy­chobi­otic Revo­lu­tion (he’s ba­si­cally the CEO of psy­chobi­otics). ‘There’s huge ex­cite­ment: peo­ple want to know what they can do with this in­for­ma­tion about how the gut in­flu­ences the brain, and we’re strug­gling to keep up.’ Let’s, for a sec­ond, put a pin in this en­thu­si­asm and back up a bit. The term ‘psy­chobi­otics’ was first coined by Pro­fes­sor Cryan and his co-au­thor, Pro­fes­sor Ted Di­nan, to re­fer to the in­flu­ence of pro­bi­otics – the bac­te­ria found in foods like live yo­ghurt and miso – on the brain. It was the work of their team that led to the sem­i­nal study in this area, which has since been cited in re­search pa­pers more than 1,000 times (science gone vi­ral). In 2011, the team fed one group of mice a strain of the bac­te­ria Lac­to­bacil­lus rham­no­sus, and an­other a bac­te­ria-free broth. Af­ter sev­eral stress tests, the team ob­served an ar­ray of changes in the bac­te­ria group, in­clud­ing al­ter­ations to neu­ro­trans­mit­ter re­cep­tors in the brain, like GABA – the same re­cep­tor tar­geted by anti-anx­i­ety drugs. They also ob­served a re­duc­tion in the anx­ious and de­pressed be­hav­iour of the mice. ‘We pro­posed that if this could be re­pro­duced in hu­mans, it would lead to a psy­chobi­otic effect,’ ex­plains Pro­fes­sor Cryan. ‘And when we did some test­ing on healthy adult vol­un­teers, the po­ten­tial psy­chobi­otics that we found did in­deed have a sig­nif­i­cant effect in low­er­ing stress re­sponse and chang­ing brain ac­tiv­ity.’


The def­i­ni­tion of psy­chobi­otics has since been broad­ened to en­com­pass any in­ter­ven­tion that in­flu­ences the brain via the gut bac­te­ria. As well as pro­bi­otic foods like yo­ghurt, this in­cludes pre­bi­otics – foods that feed your mi­cro­biome, like as­para­gus and leeks – as well as other in­ter­ven­tions like ex­er­cise. The con­vic­tion with which the mindgut con­nec­tion is spo­ken of would sug­gest that the brain and the gut are in con­stant com­mu­ni­ca­tion, the likes of which you only wit­ness in your most pro­lific group What­sapp chats. ‘The body is so in­cred­i­bly com­plex that there are many dif­fer­ent mech­a­nisms that could ex­plain how the bac­te­ria com­mu­ni­cate with the brain,’ says Dr Me­gan Rossi (@theguthealth­doc­tor), re­search associate at King’s Col­lege Lon­don. ‘We do know that there are three main path­ways. One sends mes­sages through the blood­stream by pro­duc­ing chem­i­cals in the gut; the sec­ond is through the ner­vous sys­tem; the third is like an alarm sys­tem, via im­mune path­ways.’ While it’s one thing know­ing th­ese con­nec­tions ex­ist, prov­ing how and why eat­ing a yo­ghurt could make you feel less anx­ious is an­other chal­lenge al­to­gether. In 2013, re­searchers from UCLA used func­tional MRI scan­ning to prove that when healthy women in­gested a pro­bi­otic twice daily for four weeks, it af­fected ac­tiv­ity in re­gions of the brain that con­trol emo­tion and sen­sa­tion. More re­cent stud­ies have ex­plored the po­ten­tial for ma­nip­u­lat­ing this com­mu­ni­ca­tion not only for anx­i­ety treat­ment, but also for post-natal de­pres­sion, schizophre­nia and PTSD. Though hu­man stud­ies have been small so far, find­ings sug­gest that the im­pli­ca­tions of this com­mu­ni­ca­tion ex­tend far be­yond our cur­rent com­pre­hen­sion. This could be huge. We’re in the midst of a men­tal ill­ness epi­demic – the num­ber of peo­ple taking an­tide­pres­sants has in­creased by more than 100% in the past decade. In 2016, the NHS doled out a record 64.7 mil­lion pre­scrip­tions – for con­text, there are 66 mil­lion peo­ple liv­ing in the UK. Could it be that the re­search be­ing car­ried out to­day is pav­ing the way for the use of psy­chobi­otics – yo­ghurt in­cluded – as a men­tal health treat­ment? Yes, say those knee-deep in the science. ‘I think we are head­ing to­wards a sce­nario where in five years’ time ev­ery­body will be get­ting their mi­cro­biome mea­sured in the same way that you get your choles­terol mea­sured to­day,’ says Pro­fes­sor Cryan. ‘In this sense, I think we could re­ally see a shift in pre­ven­ta­tive care, but also in treat­ment.’ A team in Canada is cur­rently re­search­ing dif­fer­ent strains of bac­te­ria with the hope of be­ing able to use mi­cro­biome anal­y­sis to pre­dict risk, but also to cre­ate be­spoke treat­ment for men­tal health con­di­tions; Pro­fes­sor Cryan’s team is also in the early stages of de­vel­op­ing a psy­chobi­otic that could be used to treat the symp­toms of mild de­pres­sion.


But oth­ers are more cau­tious when I ask if this re­search can be trans­lated into tan­gi­ble treat­ment. ‘In or­der for psy­chobi­otics to have a clin­i­cal ap­pli­ca­tion, we need more hu­man stud­ies,’ says Dr Philip Bur­net, associate pro­fes­sor in the De­part­ment Of Psy­chi­a­try at the Univer­sity of Ox­ford. ‘The prob­lem we have is that in or­der to de­ter­mine if they alone can treat some­one who has de­pres­sion, you would need to deny that per­son med­i­ca­tion. You can’t do that, which makes it very dif­fi­cult to test.’ In­stead, Dr Bur­net sees psy­chobi­otics as sup­ple­ments that can help med­i­ca­tion to work bet­ter in peo­ple who don’t re­spond well to cur­rent treat­ment or for those who have low mood but no de­pres­sion di­ag­no­sis. Adding an­other layer of com­plex­ity to psy­chobi­otics is the care that has to be taken in dis­cussing the po­ten­tial of some­thing other than tried and tested med­i­ca­tion for men­tal health. The worry is that we risk adding to the stigma that (de­spite the best ef­forts of us all – this mag­a­zine in­cluded) con­tin­ues to sur­round med­i­cally



treat­ing your mind. ‘Med­i­ca­tion has a re­ally im­por­tant role and peo­ple should never be afraid to take it if other lifestyle fac­tors aren’t work­ing,’ says Dr Rossi. ‘So I think men­tal health will al­ways call for a holis­tic ap­proach. But per­haps, ul­ti­mately, when some­one goes to their GP and re­ports symp­toms of anx­i­ety or de­pres­sion, doc­tors will pre­scribe both ex­ist­ing med­i­ca­tion and psy­chobi­otics.’ As to whether pre­bi­otics or pro­bi­otics play the big­gest role in in­flu­enc­ing men­tal health, ex­perts agree that we need more re­search on both. While they’re far from telling ev­ery­one to go out and stock up on pro­bi­otic supps, Lac­to­bacil­lus and Bi­fi­dobac­terium are among the most re­searched strains of bac­te­ria, and the con­sen­sus is that sup­ple­ments should con­tain up­wards of five bil­lion bac­te­ria per cap­sule. But they do agree on the im­por­tance of eat­ing a diet that’s rich in pre­bi­otics. That in­cludes plenty of legumes, Jerusalem ar­ti­chokes, leeks, onions and as­para­gus. Pro­fes­sor Cryan sums it up: ‘We don’t have a strong enough ev­i­dence base yet to say that pre­bi­otics have a pos­i­tive effect on the brain in hu­mans. But if you look at the Mediter­ranean diet, which is rich in pre­bi­otics, it has been proven to be ben­e­fi­cial for brain health. The miss­ing link thus far has been that this is down to your mi­cro­biome. We need to join the dots, but my gut in­stinct is telling me that, if you want to build up your stress re­silience, a psy­chobi­otic ap­proach would be use­ful.’ So, what does all this mean for peo­ple like me? While the link be­tween pre­bi­otics and brain health might need more hu­man stud­ies to de­liver con­crete proof, up­ping my in­take of pre­bi­otic foods can only be a good thing. And it’s re­as­sur­ing to know that di­etary steps could fu­ture-proof my men­tal health should I reach the point of com­ing off my med­i­ca­tion. As for where this re­search is headed, I’m ex­cited – and I’m not the only one. ‘We are in the early days of un­rav­el­ling the se­crets of this sys­tem,’ says Dr Emeran Mayer, au­thor of The Mind Gut Con­nec­tion. ‘I think we cur­rently know about 10%. But, in the next 10-20 years, this could rev­o­lu­tionise many ar­eas of medicine.’ Now, there’s food for thought.

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