REVIEW ARTICLE- published in the Journal of Gastroenterology and Hepatology
Abimosleh SM, Tran CD, Howarth GS. Emu Oil: A novel therapeutic for disorders of the gastrointestinal tract? J.
Gastro. Hepatol. 2012; 27(5):857-61
http://onlinelibrary.wiley.com/doi/10.1111/j.14401746.2012.07098.x/abstract;jsessionid=EDD42B1B23C28589B535E66C3978E111.d03t03
Emu Oil: A novel therapeutic for disorders of the gastrointestinal tract?
Suzanne M Abimosleh,*,† Cuong D Tran*,† and Gordon S Howarth*,†,‡
*Department of Gastroenterology, Women’s and Children’s Hospital, North Adelaide, †Discipline of Physiology,
School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, Adelaide, and ‡School of
Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia
Abstract
Gastrointestinal diseases characterized by inflammation, including the inflammatory bowel diseases,
chemotherapy-induced mucositis and non-steroidal anti-inflammatory drug-induced enteropathy,
currently have variably effective treatment options, highlighting the need for novel therapeutic
approaches. Recently, naturally-sourced agents including prebiotics, probiotics, plant-extracts and
marine-derived oils known to possess anti-inflammatory and anti-oxidant properties have been
investigated in vitro and in vivo. However, animal-derived oils are yet to be extensively tested. Emu
Oil is extracted from the subcutaneous and retroperitoneal fat of the Emu, a flightless bird native to
Australia, and predominantly comprises fatty acids. Despite the limited rigorous scientific studies
conducted to date, with largely anecdotal claims, Emu Oil, when administered topically and orally,
has been shown to possess significant anti-inflammatory properties in vivo. These include a CD-1
mouse model of croton oil-induced auricular inflammation, experimentally-induced polyarthritis and
dextran sulfate sodium-induced colitis. Recently, Emu Oil has been demonstrated to endow partial
protection against chemotherapy-induced mucositis, with early indications of improved intestinal
repair. Emu Oil could therefore form the basis of an adjunct to conventional treatment approaches for
inflammatory disorders affecting the gastrointestinal system.
Key words
anti-inflammatory, chemotherapy-induced mucositis, Emu Oil, fatty acids, gastrointestinal disorders,
ratite.
Introduction
A multitude of factors can influence the function of the human gastrointestinal (GI) tract including genetic
predisposition, diet composition, environmental insults and intestinal bacterial communities. Several disorders of
the GI tract, including infective enteritides (i.e. fungal, bacterial and viral gastroenteritis),1 the inflammatory
bowel diseases (IBDs; the collective term for a group of chronic, idiopathic GI disorders including ulcerative
colitis and Crohn’s disease), chemotherapy-induced mucositis,2 colorectal cancer,3 celiac disease4 and nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy,5 are associated with inflammation, ulceration,
mucosal damage and malabsorption. Current treatment options for mild to moderate ulcerative colitis comprise
anti-inflammatory drugs containing 5-aminosalycylic acid, whereas more severe conditions are treated with
corticosteroids, immunosuppressants and immunomodulators. However, these therapies are commonly associated
with significant adverse effects including infection, implicating difficulty in inducing and maintaining patient
remission.6,7 Although effective treatment options are available for a number of gastrointestinal disorders, such as
the infective enteritides, the variable responsiveness of treatments for ulcerative colitis highlights the need to
broaden therapeutic approaches, including adjunctive strategies, to attenuate the inflammatory response, prevent
mucosal damage and facilitate mucosal healing. Recently, naturally-sourced agents including probiotics,3,8,9
prebiotics,3,10,11 plant-extracts,12,13 growth factors14–16 and marine-derived oils17,18 known to possess antiinflammatory and anti-oxidant properties have been investigated as potential therapeutics. However, there have
been surprisingly few investigations of animal-derived oils in this context.
Fatty acids and intestinal inflammation
The favorable effects of diets high in n-3 fatty acids (FAs) on the cardiovascular system, particularly those found
in fish oils, were first described in Greenland Eskimos by Dyerberg et al. in 1975.19 This initial observation
prompted focused research on n-3 FAs, the predominant FAs in fish oils. These polyunsaturated FAs have been
shown to reduce levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-12
(IL-12) and interleukin-1β (IL-1β) in a severe combined immuno-deficient mouse model of colitis, a bowel
condition characterized by inflammation of the colon.20 For example, Lyprinol, an extract from the New Zealand
Green Lipped mussel, has been shown to decrease inflammation and accelerate repair of the intestinal mucosa in a
dextran sulfate sodium (DSS) model of colitis.18 Lyprinol has also improved some features of intestinal mucositis
in the experimental setting.21 However, less attention has been directed towards animal-derived oils with
purported anti-inflammatory properties, such as that derived from the Australian ratite bird, the Emu.22,23
Ratites
Ratites are flightless birds, with a raft-like breastbone devoid of a keel. In these birds, breast muscles are vestigial
to non-existent.24 The main representatives of this group are the Emu (Dromaius novaehollandiae), native to
barren regions of Australia; the African Ostrich (Struthio camelus), native to Africa; the three Kiwi species
(Apterix sp.), native to humid shady areas of the New Zealand forest; the Cassowary (Casuarius sp.), native to
New Guinea rainforests; and the Rhea or South American Ostrich (Rhea americana) and the Choique
(Pterocnemia pennata), both native to South America. Currently, certain ratites are farmed in Africa, Australia,
Canada, Europe and USA, for commercialization of their meat, skin, feathers, eggs and more recently, their oil.25
However, the composition of Rhea, Ostrich and Emu Oils, extracted from adipose tissue, is not identical.25
Indeed, a wealth of anecdotal evidence and more recent (and better controlled) experimental studies suggest that
Emu Oil may possess potent anti-inflammatory properties.23,26
Emu Oil
Emu Oil is extracted from both the subcutaneous and retroperitoneal fat of the Emu by first rendering the
macerated tissue, and then passing the liquefied fat through a series of filters to extract the oil.27 Some
manufacturers also use centrifugation to separate the oil from other extraneous components of the adipose tissue.
Native Australian Aboriginals and early white settlers first used Emu Oil to facilitate wound healing, pain
alleviation and treatment of inflamed joints.22,23 Currently, Emu Oil is readily available for purchase at health food
stores and Emu Oil companies worldwide. Manufactured products include 100% pure Emu Oil, Emu Oil capsules,
skin and hair care products, massage oil and bath and body products. Applications include the relief of
inflammatory arthritic pain in addition to itchiness, redness and irritation associated with skin conditions
including dermatitis, eczema and psoriasis. Emu Oil uniquely possesses excellent skin-permeation properties,22
highlighting its practicality for a wide range of applications, in particular, trans-dermal delivery of other
medications. Emu Oil further requires minimal refining, and presents a low health hazard, being readily
metabolizable. Its source is also renewable, eco-sustainable and relatively inexpensive.22
Emu Oil composition
Fatty acids (FAs) represent the predominating component of Emu Oil, with a lipid content of 98.8% for
subcutaneous adipose tissue, and 98.0% for retroperitoneal adipose tissue.27 Emu Oil comprises approximately
42% oleic acid (18:1 n-9), 21% linoleic acid (18:2 n-6), and 21% palmitic acid (16:0), with lower levels of other
FAs, including 1% α-linolenic acid (18:3 n-3).27,28 Emu Oil also contains variable levels of compounds including
carotenoids, flavones, polyphenols, tocopherol and phospholipids in the non-triglyceride fraction, which may
confer therapeutic benefits including antioxidant properties.22,29 More recently, Beckerbauer et al.27 demonstrated
that Emus fed a diet rich in unsaturated fat (soybean oil) produced oil that was more polyunsaturated compared
with Emus fed a diet rich in saturated fat (beef tallow). These findings indicate that diet composition can
significantly influence the composition of Emu Oil27 and hence possibly impact on oil efficacy.30
Therapeutic properties of Emu Oil
In a CD-1 mouse model of croton oil-induced auricular inflammation, topical application of Emu Oil significantly
decreased auricular thickness and weight.31 Furthermore, Emu Oil reduced levels of the pro-inflammatory
cytokines TNF-α and IL-1α,31 cytokines also reported to be directly involved in the development of IBD.32–34
Interestingly, the anti-inflammatory effects of Emu Oil in croton oil-induced auricular inflammation were more
pronounced than application of fish, flaxseed and olive oils, or liquefied chicken fat;31 oils known to contain
significantly higher levels of FAs. Snowden and Whitehouse23 assessed the anti-inflammatory activity of five
different preparations of Emu Oil, varying in Emu farm location, source of Emu adipose tissue (subcutaneous or
retroperitoneal), rendering protocols and storage. Five Emu Oil preparations (Emu Oil [EO] one; commercially
available preparation in Western Australia [WA] with added anti-oxidant, EO two; commercially rendered in WA
with no additives, EO three; prepared using intra-abdominal fat from WA birds, EO four; prepared using
subcutaneous fat from Queensland birds, EO five; commercially rendered from Queensland birds) were topically
applied to rat paws, following experimentally-induced polyarthritis. Paw diameter, indicative of arthritic
inflammation, was significantly reduced following application of four of the Emu Oil preparations (EO two-five).
Furthermore, Emu Oil preparations two and three reduced inflammation to an extent comparable with oral
ibuprofen (40 mg/kg), a readily available NSAID.23 Emu Oil has further been demonstrated to reduce plasma
cholesterol concentrations in hypercholesterolemic hamsters compared with hamsters ingesting a saturated fatty
acid-enriched diet35 and Emu Oil administration reduced plasma low-density lipoprotein and aortic cholesterol
ester concentrations.35 Whitehouse et al.22 indicated that transdermal application of Emu Oil in 15% (v/v) cineol
significantly reduced paw swelling in addition to promoting weight gain in a rat model of arthritis.
Bennett et al.29 demonstrated that Emu Oil has both antioxidant properties in vitro (radical scavenging
activities) and a protective role against oxidative damage (assessed by measuring the ability to inhibit lipid
peroxidation of erythrocytes) in a biological membrane model system. Furthermore, Emu Oil afforded greater
protection against oxidative damage than the Ostrich and Rhea Oils.29
Topical application of Emu Oil has been demonstrated to promote wound healing and recovery. In a study by
Politis and Dmytrowich,36 Emu Oil lotion (a mixture of Emu fat, oil, vitamin E and botanical oil) was applied to
full-thickness skin defects 24 h after surgery in rodents. After the major post-inflammatory stages of wound
healing had transpired (6 days postoperatively), wound contraction and infiltration of fronts of epithelialized and
granulation tissue were assessed.36 Emu Oil lotion enhanced these parameters twofold, whereas pure Emu Oil did
not exert significant effects.36 Improved wound healing with Emu Oil lotion was proposed to have occurred
through a mechanism of enhanced keratinization.36 Nevertheless, in a study by Lagniel and Torres, Emu Oil
improved recovery of damaged skin in children with second- and third-degree burn injuries caused by fire and hot
water.37
Potential mechanisms of action
The mechanism of action of Emu Oil and the nature of the active factor(s) are yet to be fully elucidated. It has
been suggested that the n-3 and n-9 FAs present in Emu Oil may confer anti-inflammatory properties,31 and
efforts to ameliorate several chronic inflammatory diseases, including IBD and rheumatoid arthritis, have been
directed towards increasing dietary intake of n-3 and n-9 FAs.18,38 n-3 FAs reduce inflammation both directly (via
downregulation of the inflammatory eicosanoid pathways that produce thromboxane B2, prostaglandin E2 and
leukotriene B4) and indirectly (by altering the expression of inflammatory genes through effects on transcription
factor activation),39 whereas n-9 FAs inhibit macrophage migration.31 Yoganathan et al.31 demonstrated that the
ability of Emu Oil to reduce levels of pro-inflammatory cytokines were more pronounced in an experimental
model of inflammation, compared with other oils known to contain higher levels of FAs. This suggests that the
anti-inflammatory properties of Emu Oil could not be solely attributed to the FA profile alone.31 It is proposed
that the effects of Emu Oil may be attributed to the synergism of FAs and other constituents in Emu Oil and/or the
FA ratio. Other minor constituents of Emu Oil in the non-triglyceride fraction, such as antioxidants including
carotenoids and flavones, and skin-permeation enhancing factors, are reported to evoke antioxidant or radical
scavenging activities,29 modulate anti-inflammatory, pro-apoptotic and anti-proliferative pathways in intestinal
epithelial cells40 and reduce pro-inflammatory cytokine production and colonic neutrophil infiltration in a mouse
model of colitis.41 Furthermore, the high ratio of unsaturated to saturated fatty acids (UFA: SFA, approximately
1.8) may confer protection against oxidative damage.29
Emu Oil and gastrointestinal disorders
Emu Oil requires extensive testing, both topically and orally, with respect to its reported therapeutic benefits.
Only in recent years have more rigorous studies of Emu Oil been conducted in pre-clinical models of gut disease.
Lindsay et al.26 proposed a potential mechanism of action of Emu Oil following oral administration to rats with
chemotherapy (5-Fluorouracil; 5-FU)-induced mucositis. In this study, Emu Oil decreased acute small intestinal
inflammation assessed by myeloperoxidase activity (found in the intracellular granules of neutrophils) 96 h after
5-FU-administration. Emu Oil also improved mucosal architecture in the small intestine by lengthening crypts to a
greater extent than the 5-FU control, during early recovery from chemotherapy-induced mucositis in rats.26 These
results highlighted the possibility of a more rapid rate of recovery following Emu Oil administration during the
long-term recovery phase of mucositis, which has not yet been tested.26 In a preliminary study in rats, Abimosleh
et al.42 indicated that orally-administered Emu Oil improved selected parameters associated with the manifestation
of DSS-induced colitis, characterized by inflammation and ulceration of the large bowel. Following Emu Oil
treatment in colitic rats, this study revealed that proximal and distal colonic crypts were significantly lengthened
to a greater extent than in colitic controls.42 Furthermore, histological damage severity observed in the proximal
and distal colon of Emu Oil-treated rats was significantly decreased, indicating a lesser degree of tissue damage.42
Importantly, this could represent a new mechanism of action for Emu Oil, suggesting therapeutic promise in the
stimulation of the intestinal repair process. Moreover, no significant effects were evident with the
13
C-sucrose
breath test in healthy rats receiving orally-administered Emu Oil, confirming the maintenance of small intestinal
functional health by Emu Oil and supporting its safety for oral administration.42 Further scientific validation of
Emu Oil for its potential to treat gastrointestinal diseases characterized by inflammatory processes should be
explored. There are well established animal models of intestinal disease43–46 and several novel methods for
detection of gastric functions. These include absorptive function,46,47 gastric emptying,48 intestinal transit49 and a
breath test for the non-invasive assessment of small intestinal mucosal injury,47 which could greatly facilitate
experimental and clinical studies associated with Emu Oil ingestion. Once the mechanism of Emu Oil action has
been confirmed in pre-clinical settings of bowel, joint or systemic inflammation, early-phase clinical trials for
these disorders would be indicated.
Conclusions
Gastrointestinal diseases and disorders that include ulcerative colitis, Crohn’s disease and NSAID-enteropathy are
characterized by intestinal inflammation, mucosal injury, ulceration and malabsorption. As current therapies for
these conditions are variably effective, the development of novel treatment strategies is desirable. Emu Oil could
therefore represent a safe, renewable and economical alternative to pharmaceutical options in this context.
Although strictly controlled extraction methods seek to minimize the impact of processing on the heterogeneity of
Emu Oil preparations, the diet, location and genetic profile of individual birds, would likely influence Emu Oil
composition and hence, clinical efficacy. To this end, further development of Emu Oil for gut disorders will
require its application to in vitro assays of physiological processes such as inflammation and intestinal barrier
function, followed by the correlation of these results with in vivo indications of efficacy. These assays could then
be used as a component of quality assurance to predict the clinical efficacy of individual Emu Oil preparations.
Moreover, future studies of Emu Oil in the context of IBD could include targeted microencapsulation, or enema
delivery methods, in an attempt to increase the bioavailability of active Emu Oil constituents at the specific site of
inflammation.
Acknowledgments
S.M.A. conducted a thorough review of the literature and prepared the manuscript. C.D.T. and G.S.H. contributed
to manuscript preparation and revision. Professor Gordon S. Howarth is supported by the Sally Birch Cancer
Council Australia Research Fellowship. The authors state that there are no conflicts of interest. This research
received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
References
1.
Lamps LW. Infective disorders of the gastrointestinal tract. Histopathology 2007; 50: 55–63.
2. Keefe DM. Intestinal mucositis: mechanisms and management. Curr. Opin. Oncol. 2007; 19: 323–7.
3. Geier MS, Butler RN, Howarth GS. Probiotics, prebiotics and synbiotics: a role in chemoprevention for
colorectal cancer? Cancer Biol. Ther. 2006; 5: 1265–9.
4. Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving
spectrum. Gastroenterology 2001; 120: 636–51.
5. Porter SN, Howarth GS, Butler RN. Non-steroidal anti-inflammatory drugs and apoptosis in the
gastrointestinal tract: potential role of the pentose phosphate pathways. Eur. J. Pharmacol. 2000; 397: 1–9.
6. Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel
disease. Clin. Microbiol. Rev. 2002; 15: 79–94.
7. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults.
Gut 2004; 53 (Suppl. 5): V1–16.
8. Peran L, Camuesco D, Comalada M et al. A comparative study of the preventative effects exerted by
three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS
model of rat colitis. J. Appl. Microbiol. 2007; 103: 836–44.
9. Menard O, Butel MJ, Gaboriau-Routhiau V et al. Gnotobiotic mouse immune response induced by
Bifidobacterium sp. strains isolated from infants. Appl. Environ. Microbiol. 2008; 74: 660–6.
10. Videla S, Vilaseca J, Antolin M et al. Dietary inulin improves distal colitis induced by dextran sodium
sulfate in the rat. Am. J. Gastroenterol. 2001; 96: 1486–93.
11. Rumi G, Tsubouchi R, Okayama M et al. Protective effect of lactulose on dextran sulfate sodium-induced
colonic inflammation in rats. Dig. Dis. Sci. 2004; 49: 1466–72.
12. Konrad A, Mahler M, Arni S et al. Ameliorative effect of IDS 30, a stinging nettle leaf extract, on chronic
colitis. Int. J. Colorectal Dis. 2005; 20: 9–17.
13. Wright TH, Yazbeck R, Lymn K et al. The herbal extract Iberogast® improves jejunal integrity in rats
with 5-Fluorouracil (5-FU)-induced mucositis. Cancer Biol. Ther. 2009; 8: 923–9.
14. Howarth GS, Francis GL, Cool JC et al. Milk growth factors enriched from cheese whey ameliorate
intestinal damage by methotrexate when administered orally to rats. J. Nutr. 1996; 126: 2519–30.
15. Howarth GS, Shoubridge CA. Enhancement of intestinal growth and repair by growth factors. Curr. Opin.
Pharmacol. 2001; 1: 568–74.
16. Howarth GS, Xian CJ, Read LC. Insulin-like growth factor-I partially attenuates colonic damage in rats
with experimental colitis induced by oral dextran sulphate sodium. Scand. J. Gastroenterol. 1998; 33:
180–90.
17. Camuesco D, Galvez J, Nieto A et al. Dietary olive oil supplemented with fish oil, rich in EPA and DHA
(n-3) polyunsaturated fatty acids, attenuates colonic inflammation in rats with DSS-induced colitis. J.
Nutr. 2005; 135: 687–94.
18. Tenikoff D, Murphy KJ, Le M et al. Lyprinol (stabilised lipid extract of New Zealand green-lipped
mussel): a potential preventative treatment modality for inflammatory bowel disease. J. Gastroenterol.
2005; 40: 361–5.
19. Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am.
J. Clin. Nutr. 1975; 28: 958–66.
20. Whiting C, Bland P, Tarlton J. Dietary n-3 polyunsaturated fatty acids reduce disease and colonic
proinflammatory. Inflamm. Bowel Dis. 2005; 11: 340–9.
21. Torres DM, Tooley KL, Butler RN et al. Lyprinol only partially improves indicators of small intestinal
integrity in a rat model of 5-fluorouracil-induced mucositis. Cancer Biol. Ther. 2008; 7: 295–302.
22. Whitehouse MW, Turner AG, Davis CK et al. Emu oil(s): a source of non-toxic transdermal antiinflammatory agents in aboriginal medicine. Inflammopharmacology 1998; 6: 1–8.
23. Snowden JM, Whitehouse MW. Anti-inflammatory activity of emu oils in rats. Inflammopharmacology
1997; 5: 127–32.
24. Angel R. A review of ratite nutrition. Anim. Feed Sci. Technol. 1996; 60: 241–6.
25. Grompone MA, Irigaray B, Gil M. Composition and thermal properties of Rhea oil and its fractions. Eur.
J. Lipid Sci. Technol. 2005; 107: 762–6.
26. Lindsay RJ, Geier MS, Yazbeck R et al. Orally administered emu oil decreases acute inflammation and
alters selected small intestinal parameters in a rat model of mucositis. Br. J. Nutr. 2010; 104: 513–19.
27. Beckerbauer LM, Thiel-Cooper R, Ahn DU et al. Influence of two dietary fats on the composition of emu
oil and meat. Poult. Sci. 2001; 80: 187–94.
28. Brown MA, Craig-Schmidt MC, Smith PC. Fatty acid composition of emu. Inform 1995; 6: 470.
29. Bennett DC, Code WE, Godin DV et al. Comparison of the antioxidant properties of emu oil with other
avian oils. Aust. J.Exp. Agric. 2008; 48: 1345–50.
30. Sales J. The emu (Dromaius novaehollandiae): a review of its biology and commercial products. Avian
Poult. Biol. Rev. 2007; 18: 1–20.
31. Yoganathan S, Nicolosi R, Wilson T et al. Antagonism of croton oil inflammation by topical emu oil in
CD-1 mice. Lipids 2003; 38: 603–7.
32. Camoglio L, Te Velde AA, Tigges AJ et al. Altered expression of interferon-gamma and interleukin-4 in
inflammatory bowel disease. Inflamm. Bowel Dis. 1998; 4: 285–90.
33. Egger B, Bajaj-Elliott M, MacDonald TT et al. Characterisation of acute murine dextran sodium sulphate
colitis: cytokine profile and dose dependency. Digestion 2000; 62: 240–8.
34. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115: 182–205.
35. Wilson TA, Nicolosi R, Handelman G et al. Comparative effects of emu and olive oil on aortic early
atherosclerosis and associated risk factors in hypercholesterolemic hamsters. Nutr. Res. 2004; 24: 395–
406.
36. Politis MJ, Dmytrowich A. Promotion of second intention wound healing by emu oil lotion: comparative
results with furasin, polysporin, and cortisone. Plast. Reconstr. Surg. 1998; 102: 2404–7.
37. Lagniel C, Torres A. Consequences of burn injuries treatment with 100% pure emu oil. Burns 2007; 33(1):
S148.
38. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator
production. Am. J. Clin. Nutr. 2000; 71 (1 Suppl.): 343S–8S.
39. Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am. J. Clin. Nutr.
2006; 83 (6 Suppl.): 1505S–19S.
40. Ruiz PA, Haller D. Functional diversity of flavonoids in the inhibition of the proinflammatory NFkappaB, IRF, and Akt signaling pathways in murine intestinal epithelial cells. J. Nutr. 2006; 136: 664–71.
41. Villegas I, Alarcon de la Lastra C, Orjales A et al. A new flavonoid derivative, dosmalfate, attenuates the
development of dextran sulphate sodium-induced colitis in mice. Int. Immunopharmacol. 2003; 3: 1731–
41.
42. Abimosleh SM, Lindsay RJ, Butler RN et al. Emu Oil increases crypt depth in a rat model of colitis. Dig.
Dis. Sci. 2012;57(4):887-96.
43. Geier MS, Tenikoff D, Yazbeck R et al. Development and resolution of experimental colitis in mice with
targeted deletion of dipeptidyl peptidase IV. J. Cell. Physiol. 2005; 204: 687–92.
44. Howarth GS, Xian CJ, Read LC. Predisposition to colonic dysplasia is unaffected by continuous
administration of insulin-like growth factor-I for twenty weeks in a rat model of chronic inflammatory
bowel disease. Growth Factors 2000; 18: 119–33.
45. Kamil R, Geier MS, Butler RN et al. Lactobacillus rhamnosus GG exacerbates intestinal ulceration in a
model of indomethacin-induced enteropathy. Dig. Dis. Sci. 2007; 52: 1247–52.
46. Howarth GS, Tooley KL, Davidson GP et al. A non-invasive method for detection of intestinal mucositis
induced by different classes of chemotherapy drugs in the rat. Cancer Biol. Ther. 2006; 5: 1189–95.
47. Pelton N, Tivey D, Howarth G et al. A novel breath test for the non-invasive assessment of small
intestinal mucosal injury following methotrexate administration in the rat. Scand. J. Gastroenterol. 2004;
39: 1015–16.
48. Symonds EL, Butler RN, Omari TI. Assessment of gastric emptying in the mouse using the [13C]octanoic acid breath test. Clin. Exp. Pharmacol. Physiol. 2000; 27: 671–5.
49. Tooley KL, Saxon BR, Webster J et al. A novel non-invasive biomarker for assessment of small intestinal
mucositis in children with cancer undergoing chemotherapy. Cancer Biol. Ther. 2006; 5: 1275–81.