Strategies to Protect

and Restore a Healthy

GIT Microbiota

Dr Jason A Hawrelak
ND, BNat(Hons), PhD, MNHAA, MASN, FACN
School of Medicine
 The Human GIT Microbiota

AKA the microbiome, microflora, or GIT ecosystem

Human gut microbiota contains 1014 viable

microorganisms (Neish, 2009)
this is 10 times the number of cells in the human body!
from over 1000 different species

a mutually beneficial symbiotic relationship

 The Human Gut Microbiota
A vital, but under-appreciated human organ

the microbiota organ

weighs 1-1.5 kg

rivals the liver in the

number of biochemical
reactions in which it
participates
From: Walter &
Ley, 2011

Annual Reviews
 The Human GIT Microbiota
Most important component of the GIT microbiota is
believed to be the colonic microbiota
bacterial concentrations far outweigh those found elsewhere
bacterial species here can be divided into potentially harmful or
beneficial groups (Gibson & Roberfroid, 1995)
 Dr Jason Hawrelak 10/10/14; Adapted from: Roberfroid et al 2010 + Gibson & Roberfroid 1995
What does our Microbiota Organ do for us?
Modulates the immune Xenobiotic metabolism
system polyphenols
protects against atopy development phytoestrogens
up-regulates non-specific immunity glycosides
and IgA production
Colonisation resistance
Normal GIT motility
Production of SCFAs
Improves nutritional status
B vitamins Production of polyamines
vitamin K Weight management
mineral absorption Cal, Mg, Zn?
energy salvaging Mood management
Helps us live longer?
 Dysbiosis
Two types of intestinal dysbiosis.
Small intestinal dysbiosis
Small Intestinal Bacterial Overgrowth (SIBO)

Colonic dysbiosis
 Agents that Damage the Colonic Microbiota

Antibiotics (Hawrelak & Myers, 2004)

Chemotherapy (Stringer et al, 2009)

Stress (Hawrelak & Myers, 2004)

Dietary factors (Hawrelak & Myers, 2004)

Agents that Damage the Colonic Microbiota
Radiotherapy (Nam et al, 2013)

Proton Pump Inhibitors (Seto et al, 2014)

NSAIDs (Montenegro et al, 2014)

 Dietary Factors that Negatively Impact
the Microbiota
Sulphates and sulphites (Hawrelak & Myers, 2004)
High protein diets (Duncan et al, 2007)

High fat diets (Cani et al, 2008)

Glyphosate (round-up) consumption (Shehata et al, 2013)

Dietary emulsifier consumption (Chassaing et al, 2015)

Sucralose consumption (Abou-Donia et al, 2008)

High in refined carbohydrates (Hawrelak & Myers, 2004)

low in microbiota foods (colonic foods/microbiota-accessible

carbohydrates)
the standard Western diet is starving our microbial self (Sonnenburg et al,
2014)
 Antibiotics
The factor with the greatest detrimental effect (Hawrelak & Myers,
2004)

NB each antibiotic has a different effect on the

microbiota

research using culturing techniques suggested quantitative

changes could last up to 40 days

alterations in microbiota function can last up to 16 months in

adults!
 Antibiotics
New research using more sensitive molecular analysis
techniques (16 sRNA) has revealed: (Jernberg et al, 2010)(Cotter, 2012)
presence of antibiotic resistant microorganisms for up to 4 years post-
treatment

alterations can last significantly longer than previously believed:

18-24 months after a single course of clindamycin
4 years after triple therapy for Helicobacter pylori !

some organisms never recover

localised extinction!
Proton Pump Inhibitors
Use of PPIs associated with:
a marked decline in microbiota diversity (Seto et al, 2014)
occurs within 7 days of beginning PPI
partly reversed 1 month post-administration
increased risk of SIBO (Lo & Chan, 2013)
increased risk of Clostridium difficile infection (Janarthanan et al, 2012)
decreased small bowel bifidobacteria concentrations (Wallace et al,
2011)

Increased protein load and putrefaction in colon due to

impaired protein digestion in upper GIT
ammonia, indoles, hydrogen sulphide & phenols
 Non-Steroidal Anti-Inflammatories
Use of NSAIDs associated
with:
increased gram-negative
bacteria concentrations (Marlicz et
al, 2014)
increased endotoxins
increased secondary bile acid
concentrations

decreased bifidobacteria and

lactobacilli concentrations
(Montenegro et al, 2014)
 How can we Protect and Maintain a
Healthy Colonic Microbiota?
Help our patients avoid factors that damage their
microbiota
dietary advice

stress management techniques

meditation
exercise

support microbiota during and after chemotherapy and

radiotherapy

avoid the use of microbiota-harming natural medicines

e.g., citrus seed extract

Encourage consumption of a diet and specific supplements

and foods that nourish and feed the microbiota
 Minimising and Restoring the
Damage from Antibiotics

Minimise antibiotic use

use only when necessary
support microbiota during and after use
Antibiotics & the GIT Microbiota
Antibiotics & the GIT Microbiota
Antibiotics & the GIT Microbiota
Antibiotics & the GIT Microbiota
Our Job is to Help the Survivors
 How can we Restore a Healthy GIT
Microbiota?
Use specific probiotic strains that enhance the growth of
your indigenous beneficial bacteria and decrease potential
pathogen populations
Bifidobacterium lactis HN019 (Ahmed et al, 2007)

Bifidobacterium lactis Bb12 (Mohan et al, 2006)

Lactobacillus casei Shirota (Ishikawa et al, 2005)

Lactobacillus rhamnosus GG (Benno et al, 1996)

Nourish & feed the survivors

Tools to Nourish & Feed the Survivors
Prebiotic supplements (Hawrelak, 2013)
a nondigestible food ingredient that beneficially affects the
host by selectively stimulating the growth and/or activity of
one or a limited number of bacteria in the colon.

Lactulose (syrup)
at least 5ml/day

GOS
at least 3g/day

FOS/inulin
at least 3g/day
 Prebiotics Improve the Microbiota
Fructooligosaccharides/ FOS (Gibson et al, 1995)

15 g/day of inulin

bifidobacteria numbers increased (P<0.001)

lactobacilli increased non-sig (P<0.075)

decrease in bacteroides (P<0.01), clostridia (P<0.05),

fusobacteria (P<0.01) and gram-positive cocci levels (P<0.001)
 Prebiotics Improve the Microbiota

FOS & inulin combo alters the colonic biofilm (Langlands et al,
2004)

7.5 g of FOS + 7.5 g inulin/day for 2 weeks prior to

colonoscopy
Prebiotic combo increased numbers of colonic mucosa-associated:
bifidobacteria
lactobacilli
eubacteria

numbers of mucosal coliforms were decreased

but not significantly so
 Prebiotics Improve the Microbiota

Lactulose
Ballongue et al 1997
20 g lactulose/day (10 g bd)
equivalent to 15ml bd of syrup

populations of Bacteroides, Clostridium, and coliforms decreased by

4.1, 2.3, and 1.8, log units, respectively (all P<0.01)

populations of Bifidobacterium and Lactobacillus increased by 3.0

and 1.2 log units (both P<0.01 compared to placebo)
 Prebiotics Improve the Microbiota
GOS
Vulevic et al 2008
5.5 g/day GOS

bifidobacteria counts increased significantly, as did faecal levels of

Lactobacillus-Enterococcus spp. (both P<0.001 compared to placebo)

numbers of Bacteroides spp., the Clostridium histolyticum group, E.

coli, and Desulfovibrio spp. all decreased (all P<0.001)
 Foods that Nourish & Restore the Gut
Microbiota
(Tuohy et al, 2012)

Whole plant foods

Polyphenol-rich foods

Prebiotic-rich foods

Prebiotic-like foods

Resistant starch-rich foods

 Whole Plant Foods
(Tuohy et al, 2012)

Whole-food, minimally processed, predominantly plant-

based diet
moderate fat
moderate protein
rich in variety
rich in fibre

Whole grains
Whole grain rice
Oats and rye (if gluten is tolerated)

Legumes

Fruits

Vegetables

Nuts
 Polyphenol-Rich Foods
(Perez-Jimenez et al, 2010)(Min et al, 2011)(Leja et al, 2013)(Ramdath et al, 2014)

Fruits
Black elderberries, black currants, blueberries
Cherries, strawberries, blackberries, plums, raspberries,
apples (red), black grapes
Nuts and Seeds
Flaxseed meal, chestnuts, hazelnuts, pecans
 Polyphenol-Rich Foods
(Perez-Jimenez et al, 2010)(Min et al, 2011)(Leja M et al, 2013)(Ramdath et al, 2014)

Vegetables
Purple carrots, red carrots, purple/red potatoes, red
cabbage, spinach, red onions, broccoli,
carrots (orange), red lettuce
Grains
Red rice, black rice, whole grain rye bread (sourdough)
Other
Black olives & olive oil
 Encourage Consumption of Prebiotic-
Rich Foods
(Hawrelak, 2013)(Biesiekierski et al, 2011)(Muir et al, 2009)(Kuo et al, 1988)

Consume foods rich in fructooligosaccharides/ inulin

(FOS) and galactooligosaccharides (GOS)
FOS
Jerusalem artichokes, yacon tubers, burdock roots, chicory roots,
dandelion roots, garlic, onions, leeks, asparagus, globe artichokes
GOS
Legumes, Brassica-family vegetables, fresh beans, beetroot, rye
sourdough (if gluten tolerated), sunflower seeds, pumpkin seeds
(pepitas), LSA mix
 Encourage Consumption of Prebiotic-
like Foods
Brown rice (Benno et al, 1989)

Carrots (Tamura, 1983)

Black currants (Molan et al, 2014)

Encourage Consumption of Prebiotic-like
Foods
Dark cocoa (Tzounis et al, 2011)

Almonds (Liu et al, 2014)

Green tea (Goto et al, 1998)

 Green Tea
Green tea (Goto et al, 1998)
300 mg catechins/day
equivalent to 5-6 cups/day
Results:
increased numbers of lactobacilli and bifidobacteria
decreased numbers of bacteroides, clostridia and
enterobacteria
decrease in faecal pH
decrease in faecal concentrations of ammonia, sulfide, skatol,
indole and cresol
increased production of SCFAs

Increased -glucosidase activity (Molan et al, 2010)

 Dark Cocoa

R, DB, PC, CO trial (Tzounis et al, 2011)

n=22 healthy subjects

Subjects consumed either high or low flavonol cocoa for 4

weeks
High = ~500 mg cocoa flavanols/day
equivalent 14 g cocoa powder/day

Results:
increase in faecal bifidobacteria and lactobacilli
decreases in clostridia
reduction in plasma triglycerides and CRP
 Encourage Consumption of
Resistant Starch-rich Foods
Legumes
Red lentils, kidney beans, adzuki beans

Bananas
less ripe = higher

Cooked and cooled potatoes

roasted > steamed
 Encourage Consumption of
Resistant Starch-rich Foods
Some other root vegetables
cassava, sweet potatoes

Rye bread

Oats
higher amounts in uncooked

Cashew nuts
 Prebiotics
Prebiotic-
like foods
FOS- & GOS-
Polyphenol rich foods
-rich foods

Dr Jason Hawrelak 10/10/14 Resistant starch-

rich foods

Dr Jason Hawrelak 10/10/14; Adapted from: Roberfroid et al 2010 + Gibson & Roberfroid 1995
 Nourish & Feed the Survivors

Ensure consumption of a variety of microbiota-

feeding foods daily

Polyphenol-rich foods

Resistant starch-rich foods

FOS & GOS-rich foods

Prebiotic-like foods
 What about Fermented Foods and
Probiotic Supplements?
Dont they feed the microbiota?

No!
Dont they repopulate the gut?

No!
Decades of research has shown clearly that you cannot
reinoculate
repopulate
populate the human gut with lactobacilli and bifidobacteria supplied by
supplements or fermented foods!
any colonisation is only temporary
 What about Fermented Foods and
Probiotic Supplements?
Reinoculation is a widely-held, but false, belief

the 4Rs of Functional Medicine

Remove
Replace
Reinoculate
Repair

Giving the right probiotic strain(s) can help protect and

restore the microbiota
but not via a permanent reinoculation
 Minimising and Restoring the
Damage from NSAIDs
Minimise use of NSAIDs
Consider alternatives:
glucosamine sulphate (long-term)
fish oil (long-term)
turmeric extracts

NSAID- and aspirin-induced GIT damage mediated by the

microbiota (Marlicz et al, 2014)
gram-negative bacteria associated with ulcer formation
lactobacilli and bifidobacteria suppress the growth of gram-negative
bacteria and prevent NSAID-induced ulcers
 Minimising and Restoring the
Damage from NSAIDs
Support microbiota during and after NSAID use

Probiotics can reduce NSAID damage (Montalto et al, 2013)

Lactobacillus rhamnosus GG (Gotteland et al, 2001)

prevents NSAID gastric erosions, but not intestinal ones

VSL#3 (Montalto et al, 2010)

reduced the increase in faecal calprotectin concentration after
indometacin administration

Lactobacillus casei Shirota (Endo et al, 2011)

reduced number of small bowel injuries when coadministered with
aspirin
 Minimising and Restoring the
Damage from NSAIDs
Support microbiota during and after NSAID use
Probiotics to help restore indigenous lactobacilli and
bifidobacteria populations
see strain list in antibiotic section

Prebiotics
Lactulose may be the prebiotic of choice given its strong ability to
reduce luminal endotoxin concentrations (Pain et al, 1986)
Endotoxins appear to play causative role in NSAID-induced
intestinal ulcerations (Syer et al, 2015)

Microbiota-nourishing foods

Eat a variety of fermented foods and some daily

 Minimising and Restoring the
Damage from PPIs
Minimise use of PPIs
Consider alternatives:
avoidance of dietary triggers

raft-forming alginates

antioxidants

turmeric extracts

melatonin
 Minimising and Restoring the
Damage from PPIs
Support microbiota during and after PPI use
Very little research done in this area

Chronic PPI users have gastric & duodenal overgrowth of

bacteria (Del Piano et al, 2012)
supplementation with Lactobacillus rhamnosus LR06, L. pentosus
LPS01, L. plantarum LP01 & L. delbrueckii subsp bulgaricus
LDD01 for 10 days
significant decrease in upper GI concentrations of enterococci,
total coliforms, E. coli, molds, and yeasts

concomitant oral supplementation with the probiotics

represents a very new strategy able to, at least partially, restore
a physiological gastric barrier effect...
 Minimising and Restoring the
Damage from PPIs
Support microbiota during and after PPI use

Probiotics that restore indigenous lactobacilli and

bifidobacteria populations
see strain list in antibiotic section

Probiotics that help prevent C. difficile infection

Lactobacillus plantarum 299v (Klarin et al, 2008)
Saccharomyces cerevisiae var. boulardii Biocodex (Surawicz et al, 2000)
Lactobacillus rhamnosus GG (Bennett et al, 1996)
 Minimising and Restoring the
Damage from PPIs
Support microbiota during and after PPI use

Probiotics that have successfully treated SIBO

Lactobacillus casei CRL 431 & L. acidophilus CRL 730 (Gaon et a,

2002)

Saccharomyces cerevisiae var. boulardii Biocodex (Goulet & Joly,

2010)

Lactobacillus casei Shirota (Barrett et al, 2008)

Bacillus clausii - Enterogermina (Gabrielli et al, 2009)

 Minimising and Restoring the
Damage from PPIs
Support microbiota during and after PPI use

Prebiotics
Lactulose addition to faecal slurries suppresses C. difficile
populations (Ito et al, 1997)
Lactulose use is associated with reduced risk of nosocomial C.
difficile infection (Rhim et al, 2008)
Inulin suppresses C. difficile growth in vitro (Marleen et al, 2003)
FOS supplementation to patients with CDAD (alongside ABs)
reduced CDAD recurrence (Lewis et al, 2005)
8.3% recurrence vs 34.3% (P<0.001)

Microbiota-nourishing foods

Eat a variety of fermented foods & daily

 We are the Custodians of the
Microbiota
It is important to protect the microbiota when we can
and restore it when the damage has already been done
Massive loss of diversity in Westerners (Schnorr et al, 2014)

Hadza vs healthy Western

3 generations of antibiotics?
Widespread use of NSAIDs and PPIs?
Western diet?
C-section births; formula feeding; anti-bacterial everything?

What we do to our microbiota can impact our entire

lineage (Blaser & Falkow, 2009)
We can only pass on the microbiota that we have!
We are the Custodians of the
Microbiota

We do not
We do not
inherit the
inherit the earth
microbiota from
from our
our ancestors,
ancestors, we
we borrow it
borrow it from
from our
our children
children
 References
Abou-Donia, M. B., E. M. El-Masry, A. A. Abdel-Rahman, R. E. McLendon and S. S. Schiffman (2008).
"Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats."
J Toxicol Environ Health A 71(21): 1415-1429.
Ahmed, M., J. Prasad, H. Gill and et al. (2007). "Impact of consumption of different levels of
Bifidobacterium lactis HN019 on the intestinal microflora of elderly human subjects." Journal of Nutrition,
Health & Aging 11: 26-31.
Barrett, J. S., K. E. Canale, R. B. Gearry, P. M. Irving and P. R. Gibson (2008). "Probiotic effects on
intestinal fermentation patterns in patients with irritable bowel syndrome." World J Gastroenterol 14(32):
5020-5024.
Bennett, R. G., S. L. Gorbach, B. R. Goldin and et al. (1996). "Treatment of relapsing Clostridium difficile
diarrhea with Lactobacillus GG." Nutrition Today 31: 35S-39S.
Benno, Y., K. Endo, H. Miyoshi, T. Okuda, H. Koishi and T. Mitsuoka (1989). "Effect of rice fiber on human
fecal microflora." Microbiology and Immunology 33(5): 435-440.
Benno, Y., F. He, M. Hosoda and et al. (1996). "Effects of Lactobacillus GG yoghurt on human intestinal
microecology in Japanese subjects." Nutrition Today 31: 9S-12S.
Biasucci, G., M. Rubini, S. Riboni, L. Morelli, E. Bessi and C. Retetangos (2010). "Mode of delivery affects
the bacterial community in the newborn gut." Early Hum Dev 86 Suppl 1: 13-15.
Biesiekierski, J.R., et al., Quantification of fructans, galacto-oligosacharides and other short-chain
carbohydrates in processed grains and cereals. J Hum Nutr Diet, 2011. 24(2): p. 154-76.
Blaser, M.J. and S. Falkow, What are the consequences of the disappearing human microbiota? Nat Rev
Micro, 2009. 7(12): p. 887-894.
Cani, P. D., N. M. Delzenne, J. Amar and R. Burcelin (2008). "Role of gut microflora in the development of
obesity and insulin resistance following high-fat diet feeding." Pathologie Biologie 56(5): 305-309.
Chassaing, B., O. Koren, J. K. Goodrich, A. C. Poole, S. Srinivasan, R. E. Ley and A. T. Gewirtz (2015).
"Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome." Nature
519(7541): 92-96.
 References
Cotter, P. D., C. Stanton, R. P. Ross and C. Hill (2012). "The impact of antibiotics on the gut
microbiota as revealed by high throughput DNA sequencing." Discov Med 13(70): 193-199.
Del Piano, M., A. Anderloni, M. Balzarini, M. Ballare, S. Carmagnola, F. Montino, M. Orsello, M.
Pagliarulo, R. Tari, L. Soattini, F. Sforza, L. Mogna and G. Mogna (2012). "The innovative potential
of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01,
and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to restore the "gastric barrier effect" in
patients chronically treated with PPI: a pilot study." J Clin Gastroenterol 46 Suppl: S18-26.
Duncan, S. H., A. Belenguer, G. Holtrop, A. M. Johnstone, H. J. Flint and G. E. Lobley (2007).
"Reduced Dietary Intake of Carbohydrates by Obese Subjects Results in Decreased
Concentrations of Butyrate and Butyrate-Producing Bacteria in Feces." Applied and Environmental
Microbiology 73(4): 1073-1078.
Endo, H., T. Higurashi, K. Hosono, E. Sakai, Y. Sekino, H. Iida, Y. Sakamoto, T. Koide, H. Takahashi,
M. Yoneda, C. Tokoro, M. Inamori, Y. Abe and A. Nakajima (2011). "Efficacy of Lactobacillus casei
treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled
study." J Gastroenterol 46(7): 894-905.
Foster, J. A. and K.-A. McVey Neufeld (2013). "Gutbrain axis: how the microbiome influences
anxiety and depression." Trends in Neurosciences 36(5): 305-312.
Francino, M. P. and A. Moya (2013). "Effects of antibiotic use on the microbiota of the gut and
associated alterations of immunity and metabolism." European Medical Journal 1: 74-80.
Gabrielli, M., E. C. Lauritano, E. Scarpellini, A. Lupascu, V. Ojetti, G. Gasbarrini, N. G. Silveri and A.
Gasbarrini (2009). "Bacillus clausii as a treatment of small intestinal bacterial overgrowth." Am J
Gastroenterol 104(5): 1327-1328.
Gaon, D., C. Garmendia, N. O. Murrielo, A. de Cucco Games, A. Cerchio, R. Quintas, S. N.
Gonzalez and G. Oliver (2002). "Effect of Lactobacillus strains (L. casei and L. Acidophillus Strains
cerela) on bacterial overgrowth-related chronic diarrhea." Medicina (B Aires) 62(2): 159-163.
 References
Gibson, G. R. and M. B. Roberfroid (1995). "Dietary modulation of the human colonic microbiota:
introducing the concept of prebiotics." Journal of Nutrition 125: 1401-1412.
Gotteland, M., S. Cruchet and S. Verbeke (2001). "Effect of Lactobacillus ingestion on the gastrointestinal
mucosal barrier alterations induced by indometacin in humans." Alimentary Pharmacology and
Therapeutics 15: 11-17.
Goulet, O. and F. Joly (2010). "[Intestinal microbiota in short bowel syndrome]." Gastroenterol Clin Biol 34
Suppl 1: S37-43.
Gronlund, M. M., O. P. Lehtonen, E. Eerola and P. Kero (1999). "Fecal microflora in healthy infants born by
different methods of delivery: permanent changes in intestinal flora after cesarean delivery." J Pediatr
Gastroenterol Nutr 28(1): 19-25.
Hawrelak, J. A. and S. P. Myers (2004). "Intestinal dysbiosis: A review of the literature." Alternative Medicine
Review 9: 180-197.
Hawrelak, J. A. (2013). Probiotics. Textbook of Natural Medicine. J. Pizzorno and M. Murray. St Louis,
Elsevier: 979-994.
Hawrelak, J. A. (2013). Prebiotics, synbiotics, and colonic foods. Textbook of Natural Medicine. J. Pizzorno
and M. Murray. St Louis, Elsevier: 966-978.
Hviid, A., H. Svanstrm and M. Frisch (2011). "Antibiotic use and inflammatory bowel diseases in
childhood." Gut 60(1): 49-54.
Ishikawa, H., et al., Randomized trial of dietary fiber and Lactobacillus casei administration for prevention of
colorectal tumors. International Journal of Cancer, 2005. 116(5): p. 762-767.
Ito, Y., H. Moriwaki, Y. Muto, N. Kato, K. Watanabe and K. Ueno (1997). "Effect of lactulose on short-chain
fatty acids and lactate production and on the growth of faecal flora, with special reference to Clostridium
difficile " Journal of Medical Microbiology 46: 80-84.
 References
Janarthanan, S., I. Ditah, D. G. Adler and M. N. Ehrinpreis (2012). "Clostridium difficile-Associated
Diarrhea and Proton Pump Inhibitor Therapy: A Meta-Analysis." Am J Gastroenterol 107(7): 1001-
1010.
Jernberg, C., S. Lfmark, C. Edlund and J. K. Jansson (2010). "Long-term impacts of antibiotic
exposure on the human intestinal microbiota." Microbiology 156(11): 3216-3223.
Kalliomaki, M., S. Salminen, H. Arvilommi and et al. (2001). "Probiotics in primary prevention of
atopic disease: a randomised, placebo-controlled trial." Lancet 357: 1076-1079.
Klarin, B., M. Wullt, I. Palmquist and et al. (2008). " Lactobacillus plantarum 299v reduces
colonisation of Clostridium difficile in critically ill patients treated with antibiotics." Acta Anaesthesiol
Scand 52: 1096-1102.
Kuo, T.M., J.F. VanMiddlesworth, and W.J. Wolf, Content of raffinose oligosaccharides and sucrose in
various plant seeds. Journal of Agricultural and Food Chemistry, 1988. 36(1): p. 32-36.
Leja, M., I. Kaminska, M. Kramer, A. Maksylewicz-Kaul, D. Kammerer, R. Carle and R. Baranski
(2013). "The content of phenolic compounds and radical scavenging activity varies with carrot origin
and root color." Plant Foods Hum Nutr 68(2): 163-170.
Lo, W. K. and W. W. Chan (2013). "Proton pump inhibitor use and the risk of small intestinal bacterial
overgrowth: a meta-analysis." Clin Gastroenterol Hepatol 11(5): 483-490.
Liu, Z., X. Lin, G. Huang, W. Zhang, P. Rao and L. Ni (2014). "Prebiotic effects of almonds and
almond skins on intestinal microbiota in healthy adult humans." Anaerobe(0).
 References
Marra, F., L. Lynd, M. Coombes, K. Richardson, M. Legal, J. M. FitzGerald and C. A. Marra (2006). "Does antibiotic
exposure during infancy lead to development of asthma?*: A systematic review and metaanalysis." CHEST Journal 129(3):
610-618.
Marlicz, W., I. Loniewski, D. S. Grimes and E. M. Quigley (2014). "Nonsteroidal anti-inflammatory drugs, proton pump
inhibitors, and gastrointestinal injury: contrasting interactions in the stomach and small intestine." Mayo Clin Proc 89(12):
1699-1709.
Maxwell, P. R., E. Rink, D. Kumar and et al. (2002). "Antibiotics increase functional abdominal symptoms." American Journal
of Gastroenterology 97: 104-108.
McFarland, L. V. and S. Goh (2013). "Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections
with probiotics: A meta-analysis." World Journal of Meta-Analysis 1(3): 102-120.
Min, B., A. M. McClung and M. H. Chen (2011). "Phytochemicals and antioxidant capacities in rice brans of different color." J
Food Sci 76(1): C117-126.
Mohan, R., et al., Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a
double-blind, placebo-controlled, randomized study. J Clin Microbiol, 2006. 44(11): p. 4025-31.
Molan, A.-L., Z. Liu and G. Plimmer (2014). "Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on
Markers of Risk for Colon Cancer in Humans." Phytotherapy Research 28(3): 416-422.
Montalto, M., A. Gallo, V. Curigliano, F. D'Onofrio, L. Santoro, M. Covino, S. Dalvai, A. Gasbarrini and G. Gasbarrini (2010).
"Clinical trial: the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy - a randomized, double-
blind, cross-over, placebo-controlled study." Aliment Pharmacol Ther 32(2): 209-214.
Montalto, M., A. Gallo, A. Gasbarrini and R. Landolfi (2013). "NSAID enteropathy: could probiotics prevent it?" J
Gastroenterol 48(6): 689-697.
Montenegro, L., et al., Non steroidal anti-inflammatory drug induced damage on lower gastro-intestinal tract: is there an
involvement of microbiota? Curr Drug Saf, 2014. 9(3): p. 196-204.
Morelli, L. (2008). "Postnatal Development of Intestinal Microflora as Influenced by Infant Nutrition." The Journal of Nutrition
138(9): 1791S-1795S.
 References
Moreau, M.-C. (2006). Immune modulation by the intestinal microbiota. Gastrointestinal Microbiology. A. Ouwehand and E.
E. Vaughan, Informa: 93-122.
Muir, J.G., et al., Measurement of Short-Chain Carbohydrates in Common Australian Vegetables and Fruits by High-
Performance Liquid Chromatography (HPLC). Journal of Agricultural and Food Chemistry, 2009. 57(2): p. 554-565.
Neish, A. S. (2009). "Microbes in Gastrointestinal Health and Disease." Gastroenterology 136(1): 65-80.
Pain, J. A. and M. E. Bailey (1986). "Experimental and clinical study of lactulose in obstructive jaundice." British Journal of
Surgery 73: 775-778.
Partty, A., M. Kalliomaki, A. Endo, E. Salminen and E. Isolauri (2012). "Compositional Development of Bifidobacterium and
Lactobacillus Microbiota Is Linked with Crying and Fussing in Early Infancy." PLoS One DOI:
10.1371/journal.pone.0032495.
Penders, J., C. Thijs, C. Vink, F. F. Stelma, B. Snijders, I. Kummeling, P. A. van den Brandt and E. E. Stobberingh (2006).
"Factors influencing the composition of the intestinal microbiota in early infancy." Pediatrics 118(2): 511-521.
Perez-Jimenez, J., V. Neveu, F. Vos and A. Scalbert (2010). "Identification of the 100 richest dietary sources of polyphenols:
an application of the Phenol-Explorer database." Eur J Clin Nutr 64 Suppl 3: S112-120.
Ramdath, D. D., E. Padhi, A. Hawke, T. Sivaramalingam and R. Tsao (2014). "The glycemic index of pigmented potatoes is
related to their polyphenol content." Food Funct.
Rhim, A. D., N. Mehta, R. Chokshi, F. Aberra, L. Gasink and Y.-X. Yang (2008). "M1206 Lactulose Use Is Associated with
Decreased Nosocomial Clostridium difficile Infection." Gastroenterology 134(4, Supplement 1): A-360-A-361.
Roberfroid, M., G. R. Gibson, L. Hoyles, A. L. McCartney, R. Rastall, I. Rowland, D. Wolvers, B. Watzl, H. Szajewska, B.
Stahl, F. Guarner, F. Respondek, K. Whelan, V. Coxam, M. J. Davicco, L. Leotoing, Y. Wittrant, N. M. Delzenne, P. D. Cani,
A. M. Neyrinck and A. Meheust (2010). "Prebiotic effects: metabolic and health benefits." Br J Nutr 104 Suppl 2: S1-63.
 References
Schnorr, S.L., et al., Gut microbiome of the Hadza hunter-gatherers. Nat Commun, 2014. 5: p. 3654.
Seto, C., et al., Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium
difficile susceptibility. Microbiome, 2014. 2(1): p. 42.
Shaw, S. Y., J. F. Blanchard and C. N. Bernstein (2010). "Association Between the Use of Antibiotics in the First Year
of Life and Pediatric Inflammatory Bowel Disease." Am J Gastroenterol 105(12): 2687-2692.
Shehata, A. A., W. Schrodl, A. A. Aldin, H. M. Hafez and M. Kruger (2013). "The effect of glyphosate on potential
pathogens and beneficial members of poultry microbiota in vitro." Curr Microbiol 66(4): 350-358.
Sonnenburg, Erica D. and Justin L. Sonnenburg, Starving our Microbial Self: The Deleterious Consequences of a Diet
Deficient in Microbiota-Accessible Carbohydrates. Cell Metabolism, 2014. 20(5): p. 779-786.
Surawicz, C. M., L. V. McFarland and R. N. Greenberg (2000). "The search for a better treatment for recurrent
Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii " Clinical and
Infectious Disease 31(4): 1012-1017.
Syer, S. D., R. W. Blackler, R. Martin, G. de Palma, L. Rossi, E. Verdu, P. Bercik, M. G. Surette, A. Aucouturier, P.
Langella and J. L. Wallace (2015). "NSAID enteropathy and bacteria: a complicated relationship." J Gastroenterol
50(4): 387-393.
Tamay, Z., A. Akcay, U. Ones, N. Guler, G. Kilic and M. Zencir (2007). "Prevalence and risk factors for allergic rhinitis
in primary school children." International Journal of Pediatric Otorhinolaryngology 71(3): 463-471.
 References
Tamura, Z. (1983). "Nutriology of bifidobacteria." Bifidobacteria Microflora 2: 3-16.
Tuohy, K. M., L. Conterno, M. Gasperotti and R. Viola (2012). "Up-regulating the Human Intestinal Microbiome Using
Whole Plant Foods, Polyphenols, and/or Fiber." Journal of Agricultural and Food Chemistry 60(36): 8776-8782.
Trasande, L., J. Blustein, M. Liu, E. Corwin, L. M. Cox and M. J. Blaser (2013). "Infant antibiotic exposures and early-
life body mass." Int J Obes 37(1): 16-23.
Wallace, J. L., S. Syer, E. Denou, G. de Palma, L. Vong, W. McKnight, J. Jury, M. Bolla, P. Bercik, S. M. Collins, E.
Verdu and E. Ongini (2011). "Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing
dysbiosis." Gastroenterology 141(4): 1314-1322, 1322 e1311-1315.
Wenus, C., R. Goll, E. B. Loken and et al. (2008). "Prevention of antibiotic-associated diarrhoea by a fermented
probiotic milk drink." Eur J Clin Nutr 62: 299-301.
Wickens, K., P. N. Black, T. V. Stanley and et al. (2008). "A differential effect of 2 probiotics in the prevention of
eczema and atopy: A double-blind, randomized, placebo-controlled trial." J Allergy Clin Immunol 122: 788-794