Mov­ing to Is­rael Might Be Mak­ing Ethiopian Jews Sick

Forward Magazine - - Genetics - By Elie Dol­gin

Yosef Yabarkan was a sixyearold boy in 1999 when he left his vil­lage in Ethiopia with his par­ents and nine sis­ters. Like tens of thou­sands of Jews be­fore them, they made the 1,600mile trek north to Is­rael. The fam­ily left be­hind a thatched hut sur­rounded by farm an­i­mals in the Tigray re­gion near the Eritrean bor­der and moved into a third-floor apart­ment in Jerusalem.

Yabarkan re­calls a happy Is­raeli child­hood filled with soc­cer games and Tal­mud stud­ies. But in his last year of high school, he started hav­ing health prob­lems. One day, dur­ing his shift at the gro­cery store where he worked at the time, he started feel­ing pangs in his gut. He went to the bath­room and then home to rest, but the pain wouldn’t go away. By the next day, Yabarkan could hardly get out of bed.

At first, doc­tors sus­pected it might be ap­pen­dici­tis. But a colonoscopy re­vealed that it was Crohn’s dis­ease.

Crohn’s is a gut dis­or­der in which the body’s im­mune sys­tem mis­tak­enly at­tacks and de­stroys healthy tis­sue in the di­ges­tive tract. Crohn’s and the closely re­lated con­di­tion ul­cer­a­tive col­i­tis are par­tic­u­larly com­mon among Ashke­nazi Jews, who have one of the high­est in­ci­dences of in­flam­ma­tory

bowel dis­ease — as the two in­testi­nal dis­or­ders are col­lec­tively known — of any eth­nic group in the world.

In Is­rael, where about one-third of the world’s Ashke­nazim live, about 1 in ev­ery 220 peo­ple — some 37,000 in to­tal — suf­fer from IBD. But in Ethiopia, Crohn’s and col­i­tis are prac­ti­cally un­heard of, among Jews and non-Jews alike.

IBD is now on the rise, how­ever, among Ethiopian Jews who have moved to Is­rael. In a study pub­lished ear­lier this year in the jour­nal In­flam­ma­tory Bowel Dis­eases, a team of lead­ing Is­raeli gas­troen­terol­o­gists de­scribed IBD as an “emer­gent dis­ease” that Ethiopian Jewish im­mi­grants need to be mind­ful of.

As doc­tors puz­zle out why pa­tients like Yabarkan are de­vel­op­ing IBD in grow­ing num­bers, they are now try­ing to raise con­scious­ness among those at risk of the health prob­lem, which can re­sult in se­vere ab­dom­i­nal pain, re­cur­rent di­ar­rhea, weight loss, hos­pi­tal­iza­tion and surgery.

“This com­mu­nity can de­velop these kinds of dis­eases even though it is very un­com­mon in Ethiopia,” said Dr. Ariella Shitrit, a gas­troen­terol­o­gist at the Di­ges­tive Dis­ease In­sti­tute of the Shaare Zedek Med­i­cal Cen­ter in Jerusalem and the lead au­thor of the new study. Ethiopian Jews “have to be aware of the symp­toms and come in for an eval­u­a­tion as soon as pos­si­ble.”

The news of the di­ag­no­sis hit Yabarkan hard. “I didn’t know how to han­dle it,” he told the For­ward, speak­ing in He­brew through an in­ter­preter. He had been look­ing for­ward to join­ing the army’s in­fantry di­vi­sion af­ter grad­u­at­ing high school. But with his med­i­cal con­di­tion — which caused him to lose more than 30 pounds — he was no longer el­i­gi­ble for army ser­vice.

“I was very frus­trated,” said Yabarkan, now 22 and study­ing to be an elec­tri­cian. “I didn’t know why it was hap­pen­ing to me.”

Prompted by cases like Yabarkan’s, Shitrit and col­leagues from seven of Is­rael’s largest hos­pi­tals con­ducted the first case-con­trol study of IBD among Ethiopian Jews in the coun­try. Over a 27-month pe­riod be­tween 2011 and 2013, the physi­cians iden­ti­fied 32 Ethiopian Jewish pa­tients with IBD (one of whom was Yabarkan). They com­pared the char­ac­ter­is­tics of these in­di­vid­u­als with an equal num­ber of Ashke­nazi Jewish pa­tients.

The doc­tors found some stark dif­fer­ences be­tween the two pa­tient pop­u­la­tions.

Whereas nearly half of the Ashke­nazi pa­tients had a rel­a­tive with the dis­ease, no Ethiopian in the study had a fam­ily history of Crohn’s or col­i­tis. What’s more, no Ethiopian was di­ag­nosed be­fore mov­ing to Is­rael; all had lived in the coun­try for at least eight years be­fore de­vel­op­ing IBD.

Genes are known to be a ma­jor de­ter­mi­nant of IBD among Ashke­nazim around the world. And Ethiopi­ans un­doubt­edly har­bor some gene vari­ants that el­e­vate their risk of de­vel­op­ing the dis­ease. How­ever, the fact that the IBD preva­lence has shot up in re­cent years among Ethiopian Is­raelis, with no con­cur­rent changes to their DNA, sug­gests that the surge in cases has more to do with dif­fer­ences in lifestyle and sur­round­ings than it does with ge­net­ics.

“Our ob­ser­va­tions sup­port the idea that en­vi­ron­men­tal fac­tors are con­tribut­ing to the eti­ol­ogy of the dis­ease,” said Shitrit, “and now we are look­ing for those fac­tors.”

There are cur­rently around 116,000 peo­ple of Ethiopian ori­gin liv­ing in Is­rael. Doc­tors es­ti­mate that 45 to 65 of these in­di­vid­u­als have been di­ag­nosed with IBD.

And IBD is not the only prob­lem on the rise. Anec­do­tal re­ports from Is­raeli doc­tors sug­gest that more and more Ethiopian Jews are also fall­ing ill with di­a­betes and celiac dis­ease. These dis­or­ders, like IBD, share a com­mon fea­ture: the im­mune sys­tem gone awry.

Many ex­perts sus­pect that the gen­eral clean­li­ness of life in Is­rael could ex­plain the uptick in these au­toim­mune dis­eases among the coun­try’s Ethiopian Jews.

“Ba­si­cally, what you are see­ing is the san­i­ta­tion hy­poth­e­sis,” said Dr. Jerome Rot­ter, a med­i­cal ge­neti­cist at the Los An­ge­les Bio­med­i­cal Re­search In­sti­tute, a not-for-profit lo­cated on the cam­pus of the Har­bor-UCLA Med­i­cal Cen­ter. This hy­poth­e­sis holds that hy­gienic en­vi­ron­ments can pre­dis­pose peo­ple to dis­eases like IBD be­cause, in the ab­sence of reg­u­lar ex­po­sure to worms, bac­te­ria and other pathogens, the im­mune sys­tem starts to er­ro­neously fight against the body’s own cells.

This idea is con­sis­tent with the ob­ser­va­tion that the preva­lence of IBD among Sephardim rose through­out the 20th cen­tury as more peo­ple moved to in­dus­tri­al­ized Is­rael from less de­vel­oped coun­tries in North Africa and the Mid­dle East.

But other fac­tors as­so­ci­ated with ris­ing liv­ing stan­dards might be in­volved as well. For ex­am­ple, changes in diet, an­tibi­otic use and vac­ci­na­tions can all neg­a­tively im­pact the com­mu­nity of mi­crobes liv­ing in our gut, with con­se­quences for the de­vel­op­ment of IBD and other au­toim­mune dis­or­ders.

To bet­ter un­der­stand the root causes of IBD among Ethiopian pa­tients, Shitrit and her col­leagues are now col­lect­ing data on the com­po­si­tion of gut bac­te­ria and var­i­ous other health met­rics. They are also look­ing at the genes of Ethiopian pa­tients.

Yabarkan hopes that these ef­forts can help ex­plain what caused him to be af­flicted with Crohn’s dis­ease in the first place. Grow­ing up in ru­ral Ethiopia, his im­mune sys­tem was prob­a­bly ex­posed to more pathogens than it is now in Jerusalem. But as a teenager in Is­rael, he also started to eat more Western-style junk food. So, what was the pri­mary driver of his dis­ease? Yabarkan con­tin­ues to won­der. But as a re­li­gious man, he has come to peace with his di­ag­no­sis. “It’s all in the hands of God,” he said.

Elie Dol­gin is a science writer in Somerville, Mas­sachusetts.

OREN ZIV

New Coun­try, New Di­ag­no­sis: Yosef Yabarkan, right, got in­flam­ma­tory bowel dis­ease af­ter he moved to Is­rael.

OREN ZIV

Na­ture or Nur­ture? Ariella Shitrit (left) wants to un­der­stand why Ethiopian Jews, like Yosef Yabarkan (right) are show­ing symp­toms of in­flam­ma­tory bowel dis­ease.

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