Gut bac­terium get­ting a closer look

Ev­i­dence in­di­cates it may of­fer health ben­e­fits as we age

Daily Press (Sunday) - - Health - BY MELISSA HEALY

Move over Bi­fi­dobac­terium and Lac­to­bacil­lus. There’s a new health-pro­mot­ing gut bac­terium in town, and it’s called Akker­man­sia muciniphila.

You will not find its ben­e­fits at the bot­tom of a yo­gurt cup. But a new study has iden­ti­fied more than one way to nur­ture its growth in the gut, and of­fered ev­i­dence that it may main­tain — and even re­store — health as we age.

Pub­lished re­cently in the jour­nal Sci­ence Trans­la­tional Medicine, the new re­search found that in mice and mon­keys whose me­tab­o­lisms had grown cranky with age, tak­ing steps to boost A. muciniphila in the gut re­duced the an­i­mals’ in­sulin re­sis­tance.

In­sulin re­sis­tance is the grad­ual im­pair­ment of the body’s abil­ity to ef­fi­ciently use food for fuel. It is best known as a way sta­tion on a pa­tient’s path to de­vel­op­ing type 2 di­a­betes.

But in­sulin re­sis­tance is also linked to a rogue’s gallery of ills, from obe­sity and in­flam­ma­tion to the sag­ging im­mu­nity and frailty that comes with ad­vanc­ing age. If a read­ily avail­able means of slow­ing or re­vers­ing in­sulin re­sis­tance could be iden­ti­fied, it might have broad and pow­er­ful anti-ag­ing ef­fects (in ad­di­tion to pro­tect­ing some of the world’s 650 mil­lion adults who are obese against de­vel­op­ing type 2 di­a­betes).

First iden­ti­fied in 2004, Akker­man­sia muciniphila in­hab­its the large in­tes­tine and is thought to ac­count for be­tween 1 per­cent and 5 per­cent of all in­testi­nal bac­te­ria in adults.

Sci­en­tists sus­pect it helps pre­serve the coat of mu­cus that lines the walls of our in­testines. It may also play a role in mak­ing the polyphe­nols we eat in plant-based foods more avail­able to our cells. Ev­i­dence is mount­ing that A. muciniphila is in­volved in obe­sity, glu­cose me­tab­o­lism and in­testi­nal im­mu­nity.

In the new re­search, a team from the Na­tional In­sti­tute on Ag­ing ex­am­ined the molec­u­lar chain of events that ap­pears to re­sult from A. muciniphila’s de­ple­tion in mice and macaque mon­keys. And they as­sessed the ef­fects of restor­ing this gut mi­crobe to el­derly an­i­mals.

First, they doc­u­mented that the guts of older an­i­mals had markedly smaller pop­u­la­tions of A. muciniphila than the guts of young an­i­mals, and that as A. muciniphila be­came more scarce, so did bu­tyrate, one of the gut’s key pro­tec­tors.

The de­fi­ciency of th­ese two sub­stances caused the mu­cous walls of the aged an­i­mals’ in­testines to thin and grow leaky. That cor­ro­sive process un­leashed a chain of events that touched off in­flam­ma­tion, prompted an im­mune re­sponse and, in a fi­nal step, in­creased in­sulin re­sis­tance.

Key to that fi­nal step was the ac­cu­mu­la­tion in the gut of a spe­cific kind of im­mune cell called 4BL cells.

If the detri­men­tal chain of events was to be dis­rupted, the ac­cu­mu­la­tion of those 4BL cells prob­a­bly had to be stopped, the re­searchers sur­mised.

The re­searchers also doc­u­mented what appeared to be a role for A.

mucini-phila in fos­ter­ing healthy di­ver­sity among the gar­den of other mi­crobes that col­o­nize the gut. In an­i­mals with scant pop­u­la­tions of A. muciniphila, a host of other com­mon gut bac­te­ria — as well as their ben­e­fi­cial byprod­ucts, par­tic­u­larly bu­tyrate — also suf­fered.

When the re­searchers gave aged mice bu­tyrate, the re­sult was higher A. muciniphila lev­els and lev­els of in­sulin re­sis­tance that ap­proached those seen in the younger an­i­mals.

They got the same re­sults when they gave aged mice and macaque mon­keys the an­tibi­otic en­rofloxacin, a broad-spec­trum an­tibi­otic used in vet­eri­nary medicine. In both an­i­mals, en­rofloxacin — which is not con­sid­ered safe for use in hu­mans — rou­tinely wiped out the 4BL cells that were thought to be a key link in the chain lead­ing to in­sulin re­sis­tance. With them out of the pic­ture, A. muciniphila lev­els rose and in­sulin re­sis­tance largely dis­ap­peared, demon­strat­ing their piv­otal role.

The re­sults sug­gest “that the in­sulin re­sis­tance and other patholo­gies as­so­ci­ated with ag­ing and even frailty can be ame­lio­rated by tar­get­ing” the cas­cade of events that flow from the de­ple­tion of of Akker­man­sia muciniphila, the study au­thors wrote.

Bel­gian re­searcher Pa­trice Cani, who is ex­plor­ing a pro­bi­otic form of Akker­man­sia that could in­crease its pres­ence in the hu­man gut, said the new find­ings are “per­fectly in line” with stud­ies that have shown the bac­te­ria’s im­pact on in­sulin sen­si­tiv­ity.

Find­ing the power of this gut bac­te­ria in macaque mon­keys is a par­tic­u­larly im­por­tant step for­ward that sup­ports “even more the need for fu­ture re­search in hu­mans,” added Cani, who is based at the Catholic Univer­sity of Lou­vain in Bel­gium.

Cani and his col­leagues have just fin­ished a small study in hu­mans to in­ves­ti­gate the safety and the fea­si­bil­ity of tak­ing Akker­man­sia in a form that will boost its pop­u­la­tions in the gut — a first.

The re­sults to date have been en­cour­ag­ing, he said.


Re­search sug­gests a de­cline in Akker­man­sia muciniphila in the gut could be re­spon­si­ble for the rise in in­sulin re­sis­tance as­so­ci­ated with ag­ing.

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