1. What’s bugging your gut? Let’s focus on the bugs!!
Christina Surawicz MD
Professor of Medicine
Division of Gastroenterology

2. Topics
What does our gut do?
What is the microbiome and what does it do?
What happens when the microbiome becomes altered?
What can we do to keep our gut healthy?

3. Our luminal GI tract
Esophagus
Stomach
Small intestine
Colon (large intestine)

4. The esophagus
Has 2 main jobs:
Get food from the mouth to the stomach and
To keep it there

5. The stomach
Grinds the food into small particles
Pass those small particles gradually into the stomach
Minor role in digesting food, producing acid to fight infections

6. Digestion and Absorption
The small intestine
Digestion and Absorption
Digests food (carbohydrates, proteins, fats) into small compounds that can be absorbed (amino acids, small sugars etc. )with the help of enzymes from the pancreas and bile from the gall bladder
Absorbs these nutrients, salt and water
chyme

7. Colon (large intestine)
Receives a liter of chyme but puts out 200 grams of stool/day—liquid to solid stool
Absorbs salt and water
Store until convenient to evacuate
Anal sphincter is the smartest sphincter
Normal: 3 BM/day to one BM every 3 days
Salvages calories from food the small intestine can’t digest like roughage

8. How does our colon salvage undigested food?
Our microbiota does it! What we used to call our gut flora….

9. What is the microbiota?
Microbes= bacteria, fungi, viruses, Microbiome=microbes and their genes
In our gut
More microbes than any other part of our body, even skin
10 x more cells than all the cells in our body
100 trillion!
1000 species

10. Our microbiome—Skin and Gut
Skin and gut each have 1,000 different bacterial strains
Encodes physiologic abilities that our own genome does not
We and our Microbiome = A Super-organism!
Washington University St Louis Genome sciences Website

11. Where does our microbiota come from?
Our gut is sterile at birth
Babies get bugs in:
Birth canal, breast milk
Environment
Food
Stable by age 3
Changes again:
Puberty
Pregnancy
Aging

12. What does Our Microbiota Do?
Carbohydrate metabolism
Bacteria ferment unabsorbed carbs, produce fatty acids that are fuel for our colon but also gas
Vitamin synthesis
Important for immune system development
More on this later– Dr. Afzali
Colonization resistance
Protects us from all the germs we ingest from the environment

13. Bacteroidetes
And
Firmicutes

14. What happens when our microbiome gets perturbed?
The biggest culprit: ANTIBIOTICS
Antibiotics - change the bacteria in the colon and cause diarrhea in 10-20%
Usually better when antibiotics are stopped
A severe form of antibiotic diarrhea is due to Clostridium difficile
A gram positive anaerobic bacteria that infects the colon

15. Clostridium difficile infection
It produces toxins that cause colon disease
It forms spores that are very hardy in the environment
Most of us don’t get sick because our colon microbiota protects us

16. Clostridium difficile infection
Since the year 2000 there has been a dramatic increase in cases – more severe, more deaths
Hypervirulent strain
Half a million cases / year in US
29,000 deaths / year in US

17. CDI cases by age
85 yo
85 +
75-84 yo
75-84

18. Common Risk Factors
Antibiotics –in prior 2 months, especially broad spectrum and multiple antibiotics
Recent hospitalization or being in a long term care facility
Age over 65
Co-morbid conditions
Immunosuppression

19. Symptoms of C difficile infection
Diarrhea
Can be mild or very severe
Usually watery
Crampy abdominal pain
Severe cases: colitis, fever, tender abdomen
When severe may require surgery to remove the sick colon
May be fatal

20. Severe Clostridium difficile infection
Normal colon
Pseudomembranes
Pseudomembranous colitis

21. Treatment of C difficile infection
Oral Antibiotics: metronidazole or vancomycin or fidaxomicin
Severe cases: need IV antibiotics
Very severe cases: may need surgery (remove colon or temporary bypass of colon)

22. Recurrent C difficile infection
Most CDI responds to standard therapy
10-20% will have a recurrence
After one recurrence, further recurrences are even more likely
These are hard to treat: using an antibiotic to treat a disease that is usually the result of an antibiotic
Vicious cycle!

23. Why does this happen?

24. Treatment of RCDI
Repeat antibiotics are needed---with metronidazole or vancomycin, but pulse suggesting that spores germinate on off days, and bugs can normalize on off days
Probiotics sometimes work

25. Russians in Caucasus lived a long time and ate a lot of yogurt
What is a probiotic?
A substance that stimulates the growth of beneficial bacteria in the alimentary and gastrointestinal tracts and that thus benefits the host as well.
Russians in Caucasus lived a long time and ate a lot of yogurt

26. Saccharomyces boulardii
A probiotic nonpathogenic yeast
We studied in 1980’s
It decreased antibiotic associated diarrhea
It treated some patients with recurrent C difficile infection
This is actually how I got interested in C diff.
But it didn’t work all the time….

27. Fecal enemas successful – 1 case
RCDI Therapy
Fecal enemas successful – 1 case
Schwan Lancet 1983
Rectal instillate of a mixture of 10 aerobic and anaerobic bacteria – 6 patients
Bacteroides restored
Tvede and Rask Madsen, Lancet 1989

28. Patient SW 42 year old woman
Retained placenta after birth of first son
Prolonged hospitalization plus antibiotics
C. difficile – 3 episodes
Rx Metronidazole x 2
Final – Vancomycin taper and Saccharomyces boulardii
Got better

29. However, 10 months after 2nd son
Diarrhea again
Recurs in 1 week, bloody
Almost continuously on Vancomycin for 9 months
3 recurrences
Vancomycin taper / pulse
Saccharomyces boulardii
Recurs within 1 week

30. Time for me to try stool transplant 2004
1990’s – my opinion: desperate patients and desperate doctors
2004 – This case: no other options
Husband donor
Delivered stool by colonoscopy
She was cured and I was convinced

31. Fecal Microbiota Transplant aka Stool Transplant
Healthy donor stool to colon via enema, colonoscopy or upper-tract
Rationale: restore normal microbiome

32. When was stool transplant first documented?
1700 years ago in China?
1958 in post op patients in Denver?
On Grey’s Anatomy in 2008?

33. Answer = A 1700 years ago in China, 4th Century used human feces to treat severe diarrhea; 16th century used infant feces, called “yellow soup” Grey’s Anatomy – 2008 “In the Midnight Hour”, done in emergency room
Zhang et al, Am J Gastroenterol 2012; 107:1755 (letter)

34. Where did this idea come from?
In 1958, a surgeon in Denver treated patients who got a severe pseudomembranous colitis after surgery with enemas of stool
They got better!
We forgot about this strategy until decades later when we started to see more severe C diff infection and nothing else was working.
We found out about the Chinese practice a few years ago

35. 90% overall for recurrent CDI Several randomized trial prove it works
How well does FMT work?
90% overall for recurrent CDI
Several randomized trial prove it works
Several routes for getting stool into the colon
Enemas
Colonoscopy
Upper GI route
NG tubes or tube into the small bowel

36. How do I do FMT?
Choose the right patient
Make sure it is recurrent CDI and that there have been proper prior treatments
Explain it is investigational but permitted by the FDA, that we cannot guarantee it will work
Find a donor

37. Usually family, friend or stool bank
Donor Selection
Usually family, friend or stool bank
Extensive initial questionnaire, like for blood donation, including
Cancer
Autoimmune disorders
Metabolic syndrome
GI disease or GI symptoms
Test blood and stool for pathogens

38. Obesity related to microbiome and diet– of mice and men/women
Microbiota from lean twin to obese mouse: mouse lost weight
Microbiota from obese twin to lean mouse: mouse gained weight
(Jeffrey Gordon’s work; Science Sept 6, 2013)
Identical twins

39. Did fecal transplant make woman obese?
32 y.o. woman gained 40 lbs. and rising after FMT for RCDI
Her BMI: 26 to 33 (thin to start)
Not able to lose the weight
Donor: 16 yo daughter was obese
Was the new colon bacteria responsible???
Alang and Kelly, Open forum infectious diseases November 2014

41. A lot of interest FMT
Remarkable efficacy for recurrent C difficile infection (90%)
A “natural” approach, simple
Special interest in inflammatory bowel disease
No immune suppression
Both C diff and IBD have dysbiosis so it might work---research being done in patients
PLEASE DON’T TRY THIS AT HOME

42. The media/lay press is full of stories of lives saved by FMT (often self-administered). There are guidebooks for patients and Online resources such as the fecal transplant foundation, “the power of poop,” and Youtube videos describe DIY FMT.

43. Some short term complications
Long term effects?
We do not know
Some short term complications
Fever, infection rare, constipation, bloating
May have long term effects
We need studies to know if FMT will be effective in other diseases

44. Wise antibiotic policies
How do we prevent CDI?
Wise antibiotic policies
Clindamycin, Cephalosporins, Quinolones are highest risk
Hand hygiene (soap and water), barrier and isolation in the hospital
Probiotics not ready for prime time in my opinion

45. How can we keep our gut healthy?
Regular meals; gut likes predictability
Avoid unnecessary medications, especially antibiotics
Exercise is good, improves transit
Healthy people don’t need probiotics
But fermented foods may be good
Kimchee, yogurt and kefir, sauerkraut

46. Healthy foods
More fruits and vegetables
Whole grains
Nonfat or low fat dairy
Seafood
Nuts
Legumes (beans, peas, lentils, etc.)

47. Avoid or limit Refined grains Processed meat Sugary sweet drinks
White bread
Processed meat
Hot dogs, ham, sausage,
bacon
Sugary sweet drinks
Soda
Red meat---3/week max
Chemicals---can’t pronounce it?
Don’t eat it.

48. Summary
What our gut does
What our microbiome does
C difficile infection
Keeping our gut healthy