ESCMID/FEMS Conference2-6 October2011 Villars-sur-Ollon, SwitzerlandNew Frontiers in Microbiology and Infection:

Helicobacter: from Basic Science to Clinical Issues.

Extra-gastric manifestation of Helicobacter infections.

Leif Percival Andersen, M.D.RigshospitaletCopenhagen.

Helicobacter species can bedivided in three groups:Gasdtric Helicobacter spp.Hepato-billiare Helicobacter spp. Intestinal Helicobacter spp.

Helicobacter species

Gastric Helicobacter spp.

H. pylori

H. heilmannii

H. bizzozeronii

H. felis ?

H. salmonii ?

Intestinal and hepaticHelicobacter ssp.

H. pyloriH. hepaticus?H. billis?

Intestinal Helicobacter ssp.

H. pyloriH. ciniadiH. fennelliae ”H. rappini”H. pullorum

H. pylori humansH. bizzozeronii dogsH. felis dogs, catsH. ciniadi rodents ”H. rappini” dogs, sheepsH. pullorum chickensH. hepaticus mice

Natural hosts for Helicobacter spp.

Iron, B12 and vitamin C deficiency Obesity and growth inhibition Pacreatitis Lever carcinoma and biliary cirrhosis Ectopic occurrence of gastric tissue Cholorectal carcinoma Diarrhoea in children Irritable Bowel Syndrome (IBD) Cardiovascular diseases Systemic sclerosis Infertility Urticaria Parkinsonism

Extragastric manifestations of Helicobacter spp.

Location of Helicobacter pylori in the stomach.

H. pylori is usually located on the surface of the gastric antralepithelial cells.

A substantial part of H. pylori is floating in the lumen of the stomach

Location of non- pyloriHelicobacter in the stomach.

H. heilmannii and other non-pyloric Helicobacter spp. are often located in the depth of the glands.

H. pylori cause a direct effect on the gastric mucosa that either prevent uptake of iron and B12 or causes an increased loss of iron in the stomach.

H. pylori has the ability actively to break down vitamin C and may thereby lead to vitamin C deficiency.

Iron, B12 and vitamin C deficiency – stomach related

Boyanova L. Future Microbiol. 2011 6:843-6.Allen LH. Food Nutr Bull. 2008 29(2 Suppl):S20-34Woodward M et al. Eur J Gastroenterol Hepatol. 2001 13(3):233-7.

H. pylori causes growth inhibition and obesity especially in children probably through the hosmones ghrelin, ghrelin o‐acyltransferaseand leptin.

Obesity and growth inhibition –stomach related

Maksud FA et al. Eur J Endocrinol. 2011 165(1):57-62. Epub 2011 Jeffery PL et al. World J Gastroenterol. 2011 14;17(10):1249-60.

H. pylori is involved in acute alcoholic pancreatitis, autoimmune pancreatitis and pancreatic carcinomas.

The involvement in acute alcoholic pancreatitis could partly be a socio-economic confounder.

The involvement in autoimmune pancreatitis could be caused by antigenic mimicry.

Pancreatitis – liver related?

Jesnowski R et al. Pancreatology. 2010;10(4):462-6. Epub 2010 Khan J et al. Scand J Surg. 2009;98(4):221-4

Helicobacter spp. is involved in billiary cirrosis and liver carcinomas. Not only H. pylori but also other hepato-billiary helicobacters can be involved.

Liver carcinoma and billiarycirrosis – liver related

Nakonieczna J et al. Diagn Microbiol Infect Dis. 2010 68(3):201-7. Epub 2010Kirchner GI et al. Int J Clin Exp Med. 2011;4(1):26-31. Epub 2010

Ectopic gastric tissue has been described in Meckel’sdiverticula and in the urinary bladder, where it has been colonized with H. pylori and even H. pylori related peptic ulcers has been described.

This may also occur in the intestine where it could facilitate the adherence of H. pylori to the intestinal mucosa.

Ectopic gastric tissue

Hill P et al. Pathology. 1998 30(1):7-9

Adhesion and coccoid forms of Helicobacter pylori.

Phagocyte urease

coccoid H. pylori

BM

BM = basal membranen

H. pylori is involved in the development of colorectal cancer.

There has especially been focus on Cag A positive H. pylori strains.

This could be through micro-areas with ectopic gastric tissue, where H. pylori has an increased ability to adhere.

Colorectal cancer – intestinalrelated

Inoue I et al. Int J Cancer. 2011 Jan 10. [Epub ahead of print]Abbass K et al. South Med J. 2011 104(7):473-6

H. pylori can cause diarrhea in chlildren. Helicobacter species is involved in

inflammatory bowel diseases (IBD).

Diarrhea and IBD – intestinal relation

Further informations in the lecture on IBD by Torkel Wadström, Sweden

Studies have shown an association between H. pylori and acute myocardial infarction and idiopathic dysrhythmias.

Other studies have not found an association between H. pylori and cardiovascular diseases.

This could partly be due to the stratification of the study groups.

Cardiovascular diseases

Christodoulou DK et al. Eur J Intern Med. 2011 22(2):191-4. Epub 2010Suzuki H et al. Helicobacter. 2011 16 Suppl 1:65-9

H. pylori is involved in systemic sclerosis and other autoimmune diseases.

A possible mechanism could be antigenic mimicry.

Systemic sclerosis – systemicrelation

Kountouras J et al. Joint Bone Spine. 2011 78(2):222-3. Epub 2011Radić M et al. Joint Bone Spine. 2011 78(4):337-40. Epub 2010

There is an association between H. pylori and chronic urticaria, trombocytopenic purpera and infertillity.

A possible mechanism could be antigenic mimicry.

Urticaria and infertility –systemic relation

Akashi R et al. J Dermatol. 2011 38(8):761-6.Ambrosini G et al. Eur J Obstet Gynecol Reprod Biol. 2011 155(2):157-60

Helicobacter species are involved in development of Parkinson’s disease.

Heliocobacter species induce interference with I-dopa. This could be caused by antigenic mimicry.

Parkonsonism – systemicrelation.

Dobbs SM et al. Helicobacter. 2010 15(4):279-94Pierantozzi M et al. Neurology. 2006 27;66(12):1824-9

The majority of the above statements are suggestions or hypothesis which need to be confirmed.

They are mainly based on sero-epidemiology or genetic based techniques.

Well-stratified patient groups are often missing. There is often a lack of a proven

pathophysiological explanation of the disease.

Extragastric maifestation of Helicobacter species.

There is a great potential for research and further knowledge about extra-gastric manifestations of Helicobacter species.

Extragastric maifestation of Helicobacter species.

Thank you