Therapeutic Potential of Fecal Microbiota Transplantation

Dr.Mohamed Shekhani

GASTROENTEROLOGY 2013;145:946–953

Introduction:• GIT contains large/diverse microorganisms, bacteria most. • At least 1014 bacteria is dominated by strict anaerobes includes

1000s of different species, many not yet cultured.• These bacteria:• Interact with the intestinal mucosa.• Influence intestinal permeability• Important for the absorption, distribution, metabolism, excretion

of nutrients• Trigger (auto) immunity.

Introduction:• The composition of the human intestinal microbiota is associated

with human health.• The composition of the intestinal microbiota can be altered with:• Diet • Prebiotics • Probiotics• Antibiotics, which produce large changes in the bacterial

composition of the intestines. • Recently with FMT.

Diet: Prebiotic effects or probiotic containing• Dietary Fiber : Nonstarch polysaccharides of plant foods poorly

digested by human enzymes.• Soluble components: pectiin, hemicelluloses, gums,mucilages; are

completely fermented by the bacterial flora• Insoluble components are cellulose, some hemicelluloses, waxes,

and lignin primarily in plant cell walls as well as resistant starch are only slightly fermented

• Some diet contains probiotics with positive effects on health as yogurt.

Diet fibers:benefits

• 1. Slows transit in small bowel• 2. Increases stool bulk• 3. Holds on to water• 4. Forms gels• 5. Binds minerals and organic substances • 6. Stimulates bacterial growth• 7. Metabolized to SCFA

Prebiotics:• Nonstarch polysaccharide or other substance supplements poorly

digested by human enzymes that that stimulate growth of bacteria:• Fructo-oligosaccharides• Inulin• Galacto-,galactosyllactose-,xylo-,isomalto-and soya oligosaccharides• Pyrodextrins (glucose oligosaccharides)• Lactulose• Breast milk oligosaccharides

Probiotics:• Human microorganisms fed as supplements that benefit the host.• Human origin• Resist upper GI tract secretions• Adhere to human intestinal cells• Colonize the human intestinal tract• Production of antimicrobial substances• Antagonize carcinogenic/ pathogenic flora • Safe in clinical use at > 1010

• Stimulate immune process• Fermentation

Probiotic Organisms in USE

• Bifidobactor sp. (bifidum, longum, breve,animalis, infantis,adolescentis)

• Streptoccus thermophilus

• Saccharomyces boulardii,cerevisiae

• Enerococcus faecium

• Lactobaciilli sp. (casei, acidophilus, bulgaricus, gaseri)

• L.rhamnosus, GG• Lactococcus sp.

(lactis,cremaris)

CLAIMS FOR PROBIOTICS

• Increase resistance to infection• Decrease duration of diarrhea disease• Stimulate immunity, modulate cytokine gene

expression, stimulate phagocytosis• Beneficial effect on blood pressure,serum

cholesterol, diabetes mellitus,lactose digestion and allergy

• Regression of tumors and reduction in carcinogens

Antibiotics: effects on intestinal microbiota

• Antibiotic –associated colitis; PMC, CDI: Clindamycin,lincomycin etc.

• Treated by Vancomycin or metronidazole.• Antibiotics used as therpay through int

microbiotal composition manipulation: neomycin,Rifazimin,metronidazole for HE.

• Metronidazole: in Crohn’s disease.• Rifaximin for IBS-DP.

FMT: History• The 1st description of human donor feces as a therapeutic agent

from China,5th century, Ge Hong, in the Handbook of Emergency Medicine , prescribed ingestion of feces for a variety of conditions.

• Ralph Lewin“: consumption of fresh, warm camel feces has been recommended by Bedouins as a remedy for bacterial dysentery;

• Its efficacy was confirmed by German soldiers in Africa during ww2”• The 1st use in mainstream medicine in 1958 for PMC/CDI by

Eiseman et al.• FMT has since increased in popularity due to its efficacy/ ease of

use for the treatment of CDI.

Methods of FMT:• FMT: the administration of a fecal solution from a donor into the

intestinal tract of a recipient. • Donor selection.• Solution preparation.• Administration of the transplant material.

Donor selection:• Healthy donors from family members or friends ,newspaper

advertisements. • Potential donors should be questioned about their travel history,

sexual behavior, previous operations, blood transfusions&other factors that increase the risk of transmissible disease.

• Sightly higher rate of disease resolution if from related donors.• No significant differences if different sex than the recipient.• Donor / recipient microbiota composition including enterotypes

could increase the efficiency of FMT.

FMT preparation:• With Water > NS ,but higher relapse.• With milk or psyllium.• 250 ml in NS.• Freshly passed within 6 hous better, but frozen banked stool nearly

similar.• Avoid electrical blender.

Route of adminstration:• Colonoscopy ,RETENTION ENEMA or OGD ,NGT,NJT.• Via colonoscopy better results.

Clinical use:• Relapsing CDI or severe CDI. • (IBD) alone or complicated by CDI• Previously unconsidered conditions

Relapsing CDI:• The antibiotic- associated R-CDI is the most common indication.• Rlapsing CDI has lower proportions of Bacteroides/ Firmicutes &

antibiotics such as metronidazole / vancomycin do not eradicate CDI in a large proportion of patients& fail to correct the underlying microbial deficiencies, but FMT does that & cures > 90%.

Severe CDI:• FMT cures it as primary trt 84% or secondary after vanco trial 90%.

CDI in IBD:• The latest ACG guidelines recommend CDI testing of all patients

hospitalized for IBD flares.

IBD:• IBD have reduced numbers of the phyla Firmicutes / Bacteroidetes

&increased numbers of Actinobacteria / Proteobacteria . • Findings indicate that remission of UC is possible with (multiple)

FMTs for a subgroup of patients. • There are currently 6 registered trials testing FMT for patients with

IBD.

IBS:• Some studies: Altered intestinal microbiota (decreased diversity

&numbers of Bacteroidetes ) in subsets of IBS.• There are 50 published cases of use of FMT to treat patients with

diarrhea-predominant IBS & chronic constipation• Substantial improvements were reported in 30 patients (60%), who

had improved defecation&an absence of bloating and abdominal pain.

CFS:• In an uncontrolled study of 60 patients with chronic fatigue

syndrome and gastrointestinal dysfunction treated with FMT, 50% had resolved sleep deprivation, lethargy, or fatigue during a 15- to 20-year follow-up period.

Metabolic/CVD:• Alterations in the composition of the intestinal microbiota have also

been associated with obesity /T2DM.• Alterations in the intestinal microbiota might contribute to the

development of cardiometabolic diseases by increasing intestinal permeability; metabolic endotoxemia , chronic inflammation

• Obese subjects have increased postprandial plasma levels of bacteria or their proteins (mainly lipopolysaccharide or endotoxin) because of increased intestinal permeability.

• FMT from lean donors significantly increased insulin sensitivity, by increasing concentrations of butyrate-producing intestinal bacteria in small & large intestine.

• FMT-based intervention studies are currently under way to see if can reduce features of fatty liver disease &vascular inflammation.

Autoimmunity:

Adverse effects:• Safe till now.• Most patients experience diarrhea on the day of infusion.• A small %: belching/or abdominal cramping or constipation.• 3 /317 (UGIB, peritonitis, enteritis).• Fever/abdominal tenderness in 3 of 4 CD patients.• Long-term follow-up studies have found that FMT is relatively free

of adverse effects.

The future:• Future research could lead to the development of specific benefi

cial (probiotic) microbes or inhibitors of specific microbes and/or their products that can improve human health via the intestinal microbiota.

SCQs:1. The intestinal microbiota can be always positively affected by the following except:A.Probiotics.B.Prebiotics.C. Antibiotics.D. Fecal microbiotic transplantation.E.Diet.

SCQs:1. The intestinal microbiota can be always positively affected by the following except:A.Probiotics.B.Prebiotics.C. Antibiotics.D. Fecal microbiotic transplantation.E.Diet.

SCQs:2. The following antibiotics can alter intestinal microbiotal composition to have positive effects on disease course except:A.Neomycin.B.Rifaximin.C. Metronidazole.D. Vancomycin.E. Lincomycin.

SCQs:2. The following antibiotics can alter intestinal microbiotal composition to have positive effects on disease course except:A.Neomycin.B.Rifaximin.C. Metronidazole.D. Vancomycin.E. Lincomycin.

SCQs:3. Fecal microbiotal transplantation had proven beneficial effects in randomised controlled trials for the following conditions except:A.CDI.B. T2DM.C. Insulin resistance.D. NAFLD.E. None of the above.

SCQs:3. Fecal microbiotal transplantation had proven beneficial effects in randomised controlled trials for the following conditions except:A.CDI.B. T2DM.C. Insulin resistance.D. NAFLD.E. None of the above.

SCQs:4. There is a better result of fecal microbiotal transplantation if the stool was taken from:A. Male.B. Female.C. Related donor.D. Unrelated donor.E. Antibiotic-treated donor.

SCQs:4. There is a better result of fecal microbiotal transplantation if the stool was taken from:A. Male.B. Female.C. Related donor.D. Unrelated donor.E. Antibiotic-treated donor.

SCQs:5. The best proven indication for fecal microbiotal transplantation is:A. Relapsed or sever CDI.B.IBD .C. IBS.D. Celiac disease.E. Liver cirrhosis.

SCQs:5. The best proven indication for fecal microbiotal transplantation is:A. Relapsed or sever CDI.B.IBD .C. IBS.D. Celiac disease.E. Liver cirrhosis.