Timo U. Kosunen

Environmental biodiversity, human microbiota, and allergy are interrelated

Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the “biodiversity hypothesis,” reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects’ homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.

Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after eradication of Helicobacter pylori.

Titres of antibody to Helicobacter pylori are known to fall with eradication of bacteria. To find out what degree of fall would reliably indicate eradication, 144 patients with Helicobacter pylori infection were given antimicrobial therapy for 2 weeks and then followed up at 6 weeks, 6 months, and 12 months with serological tests, bacterial cultures, and histological studies of gastric specimens. 6 weeks after treatment IgG titres had fallen by 20-30% irrespective of the success of bacterial eradication. In the 121 bacteria-negative patients the decrease continued. 6 and 12 months after treatment the titre was 50% or less of pretreatment value in 97% of these patients. In the 23 patients who remained infected, the initial drop of IgG titres, if any, was followed by unchanged or slightly rising titres. IgA and IgM titres, initially raised in 64% and 4% of the patients, respectively, showed similar trends. The high sensitivity (97%) of the IgG antibody tests and a consistent fall within 6 months after eradication of H pylori infection made IgG the most useful immunoglobulin class for follow-up of antimicrobial therapy in individual patients. IgA antibodies were valuable in the 2% patients who had raised titres in this immunoglobulin class only. The few patients (5.5%) who had raised IgM titres also had high IgG titres. Serological tests thus are a cheap and reliable means of monitoring success of eradication of H pylori.

Role of metronidazole resistance in therapy of Helicobacter pylori infections.

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.

Helicobacter antibodies in 1973 and 1994 in the adult population of Vammala, Finland

Changes in Helicobacter pylori seroprevalence were studied determining IgG and IgA antibodies of 408 randomly selected adults aged 15-74 years living in Vammala, Finland in 1973 and of 504 similarly selected subjects in 1994. Seroprevalence increased by age at both time points. The age-adjusted seroprevalence rate was clearly lower in 1994 than in 1973 (31 vs. 56%, P = 0.001). Paired serum samples of 224 subjects collected in 1973 and 1994 showed that the antibody status remained unaltered in 92%; 4% seroconverted and 4% seroreverted within the 21 years. The decrease in the seroprevalence rate in the population and the persistence of individual antibody status over two decades support a difference in H. pylori infection rates among birth cohorts over time rather than continuous acquisition of new infections with advancing age. Thus the risk of helicobacter infection in Vammala, Finland has been highest in childhood and continuously decreased at least for the last five decades.

Age-Dependent Increase of Campylobacter pylori Antibodies in Blood Donors

Antibodies against Campylobacter pylori were determined in 500 blood donors aged 18 to 65 years. Acid extract from a C. pylori strain was used as antigen in enzyme immunoassay. The proportion of donors with high antibody titers increased with age. For IgG antibodies it was 10% in the age group from 18 to 25 years but 60% in the group from 56 to 65 years; the increase for IgA and IgM antibodies was from 5 to 42% and from 7 to 21%, respectively. The geometric mean titers of those with high values showed no clear changes with age, which would imply chronic antigenic stimulus.

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori‐positive atrophic corpus gastritis. Duration of endoscopic follow‐up was 6 years and follow‐up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow‐up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fishers exact test). There was a small but significant (p=0.0004, Pages test) declining trend in mean atrophy score of the corpus during follow‐up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow‐up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.

The effect of Helicobacter pylori eradication on the natural course of atrophic gastritis with dysplasia

There are few data on the natural course of Helicobacter pylori‐related atrophic gastritis.

Increase of allergen‐specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections

Background The prevalence of atopic diseases – hayfever, asthma and eczema – has increased over the past decades. The increase may be associated with decreased rates of infections such as measles, hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis.

Diagnosis of Helicobacter pylori Infection in Patients with Atrophic Gastritis: Comparison of Histology, 13C-Urea Breath Test, and Serology

BACKGROUND Atrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used. METHODS We compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis. RESULTS H. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically). CONCLUSIONS H. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.Background: Atrophic gastritis, a risk factor for gastric cancer, is a late consequence of Helicobacter pylori infection in approximately one-third of the infected patients. It has been suggested that gastric cancer would develop less frequently if H. pylori were eradicated. However, the prevalence of H. pylori infection may be underestimated in patients with atrophic gastritis and intestinal metaplasia if only biopsy-based diagnostic methods are used. Methods: We compared histology, 13C-urea breath test (13C-UBT), and serology in H. pylori diagnostics in 50 male patients with atrophic corpus gastritis. Results: H. pylori was detected in 15 (30%) patients by histology and in 14 (28%) by 13C-UBT, whereas increased serum antibody levels indicating H. pylori infection were found in 41 (82%) patients (P < 0.0001 between serology and both histology and 13C-UBT). H. pylori infection was associated with atrophic corpus gastritis in 84% of the present patients (in one patient with normal antibody titres H. pylori was defined histologically). Conclusions: H. pylori infection would have been missed in most patients with atrophic gastritis without the analysis of H. pylori antibodies. Therefore, in patients with atrophic gastritis, the use of serology is encouraged in diagnosing H. pylori infection.

Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland.

The in vitro susceptibilities of 102 human campylobacter strains isolated between 1978 and 1980 and 100 strains isolated in 1990 to ciprofloxacin, norfloxacin, erythromycin, gentamicin, and doxycycline were examined. The biotypes and heat-stable serotypes of the strains as well as antimicrobial treatments and travel history of the campylobacter-positive patients were also studied. The results indicated that susceptibility to erythromycin, gentamicin, and doxycycline has remained the same during the past 10 years. No gentamicin-resistant strains were found. Resistance to erythromycin was 3% in both groups of strains. However, the number of norfloxacin-resistant strains increased from 4 to 11% in the follow-up period, and ciprofloxacin-resistant strains, which had not occurred 10 years ago, composed 9% of the strains isolated in 1990. Thus, the increase of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli has been significant in Finland in the past 10 years.