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Fungal-type dysbiosis. Medical Information. (Rev. 01/10) Dr Keith Eaton, Consultant Allergist Introduction In spite of recent work over the past decade this condition remains a controversial diagnosis, due more to medical inertia rather than an absence of data, which currently (and work continues) includes over 15 papers and two book chapters. The main factor contributing to this inertia is an unfortunate mis-labelling which took place in the 1970s. The condition has a long history having been described by Hurst in 1930(1) as Intestinal Carbohydrate Dyspepsia: this faded from view in the 1950s because of lack of research. When it was revived by Truss in the 1970s(2) he had developed a thesis that it was caused by Candida albicans and unfortunately put this forward as part of a new name. Regrettably, he did so in such a way as to imply that his theory was established fact, with the predictable result that orthodox medicine rejected the entity: its subsequent unquestioning acceptance by alternative practitioners made matters still worse. Subsequently there have been a number of published peer review research studies which should have engendered a reappraisal. The current preferred name is FUNGAL-TYPE DYSBIOSIS (FTD)(3), which should replace older terms such as abnormal gut fermentation and dysfunctional gut syndrome(4). It is an organic illness which often responds well to a specific management regime.

The clinical syndrome Although never known to be fatal FTD causes considerable morbidity and patients who do not receive specific treatment typically have the "thick notes" syndrome. They have often had multiple consultations and many negative investigations and are often on several drugs with little or no benefit. Clinically FTD embraces any or all of abdominal (IBS) symptoms, allergic responses including urticaria and catarrhal symptoms, general malaise which may overlap with chronic fatigue syndrome and minimal psycho-neurological dysfunction including brain "fog" and "fag" and inability to concentrate(5). With appropriate treatment they may often become well and not need significant aftercare(6). Broad spectrum antibiotics may be aetiologically involved(7). These are known to adversely affect colonic flora (Professor R. Lacey, Leeds, personal communication 1994). Phenoxymethyl penicillin, erythromycin and metronidazole give least problems. The concurrent administration of broad spectrum antibiotics during treatment for FTD may cause relapse. Female sex hormones (the pill, HRT), may relate both to onset and failure to respond (Grant, E. Kingston-on-Thames, personal communication 1997). Systemic steroids may be aetiologically related and impair response to treatment. 1 of 3

Research Studies The key to many subsequent studies is the establishment that the untreated patients produce small (up to 250 microgrammes) of blood ethanol when fasting patients receive a 2G. enteric coated dextrose challenge(8,9). This currently remains the most useful laboratory confirmation of the diagnosis and is available from Biolab (0207 636 5959), who can analyse postal samples. Some patients who would respond to treatment (see below) may be negative, but a positive is strong presumptive evidence of illness. The ethanol levels are well below those involved in drink driving offences: FTD is not normally a valid defence to such a charge. Current procedure uses gas-liquid chromatography which enables levels of higher alcohols and short-chain fatty acids (SCFA) to be part of the profile. Production of these is a normal phenomenon(10) and part of the process whereby "soluble" fibre is metabolised by commensal gut bacteria into SCFA which are absorbed as food: raised levels are an indication of bacterial dysbiosis, common in partially treated FTD. Patients with FTD handle sugars differently from those with food intolerance (type B food allergy)(11). They have defective absorption of micronutrients(12,13) and increased gut permeability(14). They have abnormal amino acid levels(15,16), especially B-alanine excretion(17). Histidine metabolism is a marker of allergic status (urinary excretion is lowered when histamine demand increases) and FTD patients have similar levels to those with classical (type A) or type B allergy(18). Dietary restrictions are justified by epidemiological studies(19,20) and by a re-introduction study(21). Stool cultures in a patient with a pre-existing ileostomy fail to demonstrate growth of any yeast, including Candida albicans(22). Breath hydrogen estimations show the same elevated levels in FTD and bacterial dysbiosis(23). The results of these studies fail to show any yeast involvement (although they do not exclude it) and suggest that the aetiology may involve functional abnormalities of bowel flora inducing allergic response mechanisms. Recent work supports a bacterial element by establishing raised levels of higher alcohols, but did not show any diminution of gastric acid production (associated with severe allergic states) or reduced exocrine pancreatic production(24). The mechanisms are clearly complex, and the same clinical syndrome may have different microbiological origins in individual patients(19,20). These processes are,at present, imperfectly understood(25). It would however be crass, with this wealth of abnormalities of biochemical functions to suggest that the processes of FTD could be entirely of psychological origin.

Patient Management Currently this remains mainly dependent on dietary restriction of fermentable, yeasty and mouldcontaining foods. Modest levels of vitamin/mineral supplementation are required. The regime has been developed in cooperation with highly experienced dieticians and is regarded by them as being safe for moderate to long term use. The majority will respond well to this, but those who do not make adequate progress may need concurrent antifungal drugs, bacterial growth factors (prebiotics(26)) and low dosage desensitisation. A study, criticised at the time for poor methodology(27), appeared to show no benefit from antifungal drugs(28). This trial, however, omitted any appropriate dietary regime. A more recent and more careful double-blind controlled trial now shows significant benefit in reducing symptoms scores both for diet, the antifungal nystatin and the two combined. It. should be noted that the gain from the antifungal on its own was the least, with combined treatment giving the best results(29). After a few months most patients will become well and need no or minimal aftercare.

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References 1) Hurst, A.F. and Knott, F.A. Intestinal Carbohydrate Dyspepsia. Quart. J. Med. 1930-31; 24:171-180. 2) Truss, C.O. Tissue injury induced by C. albicans: mental and neurological manifestations. J. Orthomolecular Psychiatry. 1980; 7:17-37. 3) Anthony, H., Birtwistle, S., Eaton. K. and Maberly, J. Environmental Medicine in Clinical Practice. BSAENM Publications, Southampton. 1997: 141-157. 4) Eaton, K.K. Gut Fermentation. J. Nutr. Environ. Med. 1995; 5: 206-207. 5) Eaton, K.K. Gut fermentation: a reappraisal of an old clinical condition with diagnostic tests and management: discussion paper. J. Roy. Soc. Med. 1991;84: 669-671. 6) Anthony, H., Birtwistle, S., Eaton. K. and Maberly, J. Environmental Medicine in Clinical Practice. BSAENM Publications, Southampton. 1997: 314-315. 7) Alun-Jones, V., Wilson, A.J., Hunter, J.O. and Robinson, R.E. The aetiological role of antibiotic prophylaxis with hysterectomy in irritable bowel syndrome. J. Obst. Gyn. 1984: (suppl. 1): S22-23. 8) Hunnisett, A., Howard, J. and Davies, S. Gut Fermentation (or the "Autobrewery" Syndrome): a Clinical Test with Initial Observations and Discussion. J. Nutr. Med.1990; 1: 33-38. 9) Howard, J. The "Autobrewery" Syndrome. J. Nutr. Med. 1991; 2: 97-98. 10) McNeill, N.I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 1984; 39: 338342. 11) Eaton. K.K. Sugars in Food Intolerance and Gut Fermentation. J. Nutr. Med. 1992; 3: 295-301. 12) Galland, L. Nutrition and Candidiasis. J. Orthomolecular Psychiatry 1985; 15: 50-60. 13) Eaton, K.K., McLaren-Howard, J., Hunnisett, A. and Harris, M. Abnormal gut fermentation: laboratory studies reveal deficiency of B vitamins, zinc and magnesium. J. Nutr. Biochem. 1993; 4: 635-638. 14) Eaton, K.K., Howard, M. and McLaren-Howard, J. Gut permeability measured by polyethylene glycol absorption in abnormal gut fermentation as compared with food intolerance. J. Roy. Soc. Med. 1995; 63-66. 15) Truss, C.O. Metabolic Abnormalities in Patients with Chronic Candidiasis: the Acetaldehyde Hypothesis. J. Orthomolecular Psychiatry 1983; 13:66-92. 16) Eaton, K.K. is there an allergic and fermentative gut condition, and does it relate to Candida? In: Food Allergy and Intolerance (eds.) Brostoff, J. and Challacombe, S.J. Saunders, London (2nd. edn.) In Press. 17) Eaton, K.K., Howard, M. and Hunnisett, A. Urinary B-alanine is a Marker of Abnormal as well as Normal Gut Fermentation. J. Nutr. Med. 1994; 4: 157-163. 18) Eaton, K.K., Howard, M. and Hunnisett, A. urinary histidine excretion in classical (type A) allergy, food intolerance (type B allergy) and fungal-type dysbiosis. J. Nutr. Biochem. 1998; 9: 586-590. 19) Hyland, M.E.and Sodergren, S.C. Relationship between Lifestyle and Minor Health Complaints: Evidence for Two Different Types of Gut Microflora. J. Nutr. Environ. Med. 1998; 7: 253-265. 20) Hyland, M.E. and Sodergren, S.C. Relationship between Lifestyle and Minor Health Complaints: Evidence for Two Clusters of Association. J. Nutr. Environ. Med. 1998; 8: 233-246. 21) Eaton, K.K. and Howard, M. Fungal-type Dysbiosis of the Gut: the Occurrence of Fungal Diseases and the Response to Challenge with Yeasty and Mould-containing Foods. J. Nutr. Environ. Med. 1998; 8: 247-255. 22) Eaton, K.K. Do Yeasts play any part in "Candida" (Fungal-type dysbiosis)? Discussion Paper. J. Nutr. Environ. Med. 1999; 9: 323-327. 23) Eaton, K.K., Chan, R., Howard, M. and McLaren-Howard, J.M. A Comparison of Lactulose Breath Hydrogen Measurements with Gut Fermentation Profiles in patients with Fungal-type Dysbiosis. J. Nutr. Environ. Med. 2001; 11: 33-42. 24) Eaton, K.K., Gaier, H.C., Howard, M., McLaren-Howard, J. and Reid L. Gastric Acid Production, Pancreatic Secretions and Blood Levels of Higher Alcohols in Patients with Fungal-type Dysbiosis of the Gut. Paper submitted for publication, 2001. 25) Schrader, W.A. Dysbiosis: A Generation On. (Editorial). J. Nutr. Environ. Med. 2001; 11: 5-7. 26) Kritchevsky, D. Phytosterols. In: Dietary Fiber in Health and Disease. (eds.) Kritchevsky, D. and Bonfield, C. Plenum Press, New York. 1997: 235-243. 27) Anonymous. Editorial. New Engl. J. Med. 1990; 323: 1619. 28) Dismukes, W.E., Wade, J.S, Lee, J.Y. et al. A randomised double blind controlled trial of nystatin therapy for the candidiasis sensitivity syndrome. New Eng. J. Med. 1990; 323: 1717-1723. 29) Santleman, H., Laerum, E., Roennevig, J and Fagertun, H.E. Effectiveness of nystatin in polysymptomatic patients. A randomised, double blind trial with nystatin versus placebo in general practice. Family Practice 2001; 18: 258-265.

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