a

Bile Acid Malabsorption and Fecal Bile Acids Testing [Hot Topic]

welcome to mail medical laboratories hot

topics these presentations provide short

discussion of current topics and may be

helpful to you in your practice our

speaker for this program is dr. Leslie

Donato an instructor in laboratory

medicine and pathology at Mayo Clinic as

well as a consultant and cardiovascular

at laboratory medicine and also the

clinical Corps laboratory dr. Donato

provides an overview of the new

fractionated fecal bile acids test

thank you dr. Donato for presenting with

us today thank you for the introduction

I have nothing to disclose as you view

this presentation

consider the following important points

regarding bile acids fractionated fecal

be a 48 F how is the testing going to be

used in your practice when should the

test be used and how will results impact

patient management in this session I

will describe a new test for probing the

etiology of a condition called irritable

bowel syndrome or IBS irritable bowel

syndrome is characterized by abdominal

pain or discomfort with defecation and

also changes in bowel habits or

disordered defecation it is quite common

with 10 to 20% of the worldwide

population displaying symptoms of IBS it

is estimated to be the cause of up to

50% of all GI referrals and is the

second highest cause of work absenteeism

second only to the common cold the

diagnostic criteria used to identify IBS

utilizes only patient symptoms and is

defined by the rhone 3 criteria as

outlined on the right hand side of the

screen there are four types of irritable

bowel syndrome IBS with predominantly

diarrhea IBS with predominantly

constipation mixed IBS with varying

diarrhea and constipation and unsub

typed IBS we will focus today on IBS

diarrhea or IBS d IBS D is not a

straightforward diagnosis

stools may be solid but frequent

straining to defecate can occur with

soft or watery stools

lastly symptoms can overlap with celiac

disease food allergies and even healthy

individuals patients with mild to

intermittent symptoms may benefit from

treatment including lifestyle and

dietary modification which would include

avoiding foods that are gas producers

contain lactose or gluten etc patients

with moderate to severe symptoms often

require from a collage achill therapies

such as the ones listed here for

patients with IBS diarrhea up to 30% of

IBS D patients have a condition called

bile acid malabsorption let's discuss

the biological function of bile acids

bile acids aid in the emulsification and

absorption of dietary fats they are

synthesized from cholesterol in the

liver and stored in the gallbladder upon

ingestion of a meal they are secreted

into the intestine where they carry out

their function to transport dietary fats

through the GI system a majority of bile

acids about 95 percent are then

reabsorbed in lower GI tract only the

remaining 5% of bile acids can be found

in stool bile acids that are released

from the gall bladder are called primary

bile acids as they make their way

through the GI system intestinal

bacteria convert primary bile acids to

secondary bile acids the majority of

bile acids found in stool are secondary

bile acids with a small percentage of

primary bile acids remaining the five

most prevalent bile acids found in stool

are shown in the table above bile acid

malabsorption is a condition in which

insufficient bile acid reabsorption or

overproduction of bile acids leads to

increased bile acids in the stool it can

be separated into

types type one is caused by allele

dysfunction and impaired reabsorption

for example Crohn's disease type 2 is

primary or idiopathic caused by an

increase of bile acid production the

last is type 3 which consists of other

gastrointestinal disorders which affect

absorption such as small intestinal

bacterial overgrowth celiac disease or

chronic pancreatitis so the question is

how can a physician differentiate cases

of increased fecal bile acids from other

causes of IBS diarrhea high fetal bile

acids can be found in patients with IBS

diarrhea from several causes including

bile acid malabsorption increased bio

acid synthesis and increased colonic

transit it is estimated that up to 30%

of all patients with IBS diarrhea have

increased bile acids in their stool the

testing we offer to identify high fetal

bile acids includes two results the

first is the total amount of fecal bile

acids in which all five of the most

abundant fecal bile acids are measured

separately and then added together the

second reported result is the percentage

of the primary bile acids the cola

Cassatt and Kino deoxycholic acid as a

percent of the total fecal bile acids an

elevated value of either total bile

acids or primary bile acids is

indicative of bile acid malabsorption

total bile acids are increased because

of the reasons stated on the top of this

slide the primary bile acids are

increased most likely because of a

decreased rate of conversion of primary

to secondary bile acids as colonic

transit rate increases the potential

pharmaceutical treatment for patients

with bile acid malabsorption include

bile acid sequestrants which complex to

bile acids and prevent their

reabsorption such that the body excretes

more bile acids in the stool

so drugs called FXR agonist can be used

which function to decrease the synthesis

of bile acids historically if a patient

was thought to have bile acid

malabsorption a physician may choose to

empirically treat with one of these

treatments most commonly a bile acid

sequestrants

in the hopes to relieve the patient's

symptoms however the empirical treatment

of patients without knowing they have

bile acid malabsorption can be

problematic for a variety of reasons

including adverse side effects and poor

patient tolerability therefore

identifying patients that could benefit

from treatment would be ideal in our own

internal studies we identified a cohort

of patients diagnosed with IBS d that

also had elevated fecal bile acid values

they were enrolled in an open labeled

10-day single-dose trial of the bile

acid sequestrants avawam in this slide

you'll see that nearly all patients had

an improvement of their stool form as

measured by the Bristol stool form scale

the test for fecal bile acids starts

with a time stool collection the timed

collection requires a 100 gram per day

fat diet for two days prior to

collection and also during the time of

collection for a total of four days on

the high-fat diet the collection of all

past stools occurs on day three and four

of the high-fat diet for a total of 48

hours the combined sample is either

brought to the laboratory if the patient

is local or the sample is mailed to the

lab one important aspect of sample

collection is that the collected stool

must be kept cold

preferably frozen until delivered to the

lab this means that mailed stool samples

should be mailed frozen to the

laboratory

once the 48-hour stool collection is

received in the lab the sample is

homogenized the bile acids are extracted

from the stool and are then measured

using liquid chromatography separation

with

mass spectrometer detection the assay

measures the five most abundant fecal

bile acids found in stool as a reminder

the test results that the physician

receives include two reported values the

first is the total amount of fecal bile

acids contained in the entire 48-hour

collection and the second is the percent

of the primary fecal bile acids bile

acid malabsorption is suggested if

either value is elevated to interpret

the total bile acids in the sample the

upper limit of the central 95th

percentile for total fecal bile acids of

a healthy reference population is used

this upper limit is 2619 micromoles per

48 hours to interpret the percent of

primary bile acids an internal study was

performed that showed a value of 3.7

percent or more of primary bile acids in

the feces is 90 percent specific and 72

percent sensitive to detect ibs-d

over healthy controls lastly it is

important to take note of a few

important considerations when ordering

the fecal bile acid test first patients

currently taking or have recently been

treated with systemic antibiotics will

have reduced conversion of primary to

secondary bile acids this is because

intestinal bacteria convert primary bile

acids to secondary bile acids patients

on antibiotics which function to kill

bacteria will have extremely elevated

primary bile acids in their stool that

is not the result of bile acid

malabsorption it may take up to three

months to restore the microbiome in

these patients such that normal

conversion of primary to secondary bile

acids can occur second patients with

severe liver disease or dysfunction will

have low total bile acids this is

because bile acids are produced in the

liver so patients with a malfunctioning

liver will have low total bile acids in

their stool third a random stool sample

is not acceptable for testing all

laboratory and clinical Val

datian studies were performed with

48-hour timed collections and an

internal study proved that a random

stool collection did not give the same

results as the time collection

lastly the fecal bile acids tests can be

ordered along with a 48-hour fecal fat

test this is because they require the

same patient preparation and the same 48

hours tool collection physicians that

want to order both a fecal fat test and

a fecal bile acids test on the same

patient to assess the cause of their

chronic diarrhea can do so on the same

order if the fecal fat is a 48-hour

duration