From THE DEPARTMENT OF MICROBIOLOGY, TUMOR AND CELL BIOLOGY (MTC) Karolinska Institutet, Stockholm, Sweden Biochemical parameters reflecting the intestinal ecology of healthy adults and alterations of these parameters in patients with ulcerative colitis or rheumatoid arthritis

The gastrointestinal microflora, the largest single collection of cells in the body, influence their human host in a variety of ways. Useful in this connection is the concept of Microflora-Associated Characteristics (MACs), which are defined as any anatomical structure or physiological, biochemical or immunological function in the host that is affected by the microflora. In the present investigation we have established and evaluated reliable reference values for three MACs, i.e., the conversion of cholesterol to coprostanol, content of urobilinogens and tryptic activity (FTA) in faecal samples. Ours is the largest study of its kind to date, assessing these parameters in more than 560 healthy men and women (HS; Healthy Subjects) and analyzing the findings with respect to both gender and age (employing arbitrary division into groups < 36, 36-50 and > 50 years old). Conversion of cholesterol to coprostanol in 633 HS; In general, the proportion of men with the highest conversion rate was found in the oldest age group in contrast to women were the conversion was of the same order of magnitude, irrespectively of age group. One possible explanation for these observations might be that men with low or no converting capacity in the oldest age group are lost in this cohort of HS. However, to rule out whether the capacity to convert cholesterol is related to morbidity requires additional long-term studies. Formation of urobilinogens in 562 HS; In general, the levels of urobilinogens were higher in men irrespectively of age group. Both bilirubin and its metabolites – urobilinogens – undergo enterohepatic circulation and thereby provide an interesting endogenous model for xenobiotics. The reference values found in this study might be of value when evaluating metabolism of xenobiotics in relation to gender and age. Degradation of FTA in 573 HS; In general, the mean levels were highest in the youngest male group and decreased successively in the two older groups. Although the same tendency was observed among the women, at all ages the men demonstrated higher mean values. FTA appears to be an important regulator of the intestinal flora by activating defensins. The clinical relevance of these findings in patients with inflammatory bowel disease should be explored in greater details. Determination of these same MACs in patients suffering from Ulcerative Colitis (UC) or Rheumatoid Arthritis (RA): Irrespective of the extent to which their disease had spread, patients suffering from UC exhibited less formation of coprostanol, reduced levels of urobilinogens and elevated levels of FTA in comparison to HS. For ethical reasons we could not clarify the influence of SalicylAzoSulphaPyridine (SASP; sulphasalazine) on these variables. Thus, patients with RA treated with SASP were evaluated with respect to these MACs as well. Patients with RA who were not receiving SASP demonstrated a higher frequency of high converters of cholesterol to coprostanol in comparison to a genderand age-matched group of HS. Treatment with SASP in patients with RA tended to reduce the coprostanol formation but markedly reduced the levels of urobilinogens and increased the FTA values compared to the untreated patients with RA. Consequently, it appears likely that the alterations observed in patients with UC are also induced by SASP, which seems thus to exert a general influence on the cross-talk between different types of microbes and between microbes and the host which goes on continuously in the gastrointestinal tract.