Parkinson's disease (PD) is a neurodegenerative amyloid disorder with debilitating motor symptoms due to the loss of dopamine-synthesizing, basal ganglia-projecting neurons in the substantia nigra. An interesting feature of the disease is that most of PD patients have gastrointestinal problems and bacterial dysbiosis, years before the full expression of motor symptoms. We hypothesized that antibiotic consumption might be a contributing factor of gut microbiome dysbiosis in PD, favoring curli-producing Enterobacteria. Curli is a bacterial α-synuclein (αSyn) which is deposited first in the enteric nervous system and amyloid deposits are propagated in a prion like manner to the central nervous system. In addition, antibiotics result in a low-grade systemic inflammation, which also contributes to damage of neurons in enteric- and central nervous system. To support our hypothesis, by comparing PD prevalence change with antibiotic consumption data in EU countries, we found significant positive correlation between use narrow spectrum penicillin + penicillinase resistant penicillin and increased prevalence of the disease.

Parkinson’s disease: Parkinson’s disease (PD) is the second-most common neurodegenerative disease, affecting at least 0.3% of the worldwide population and over 3% of those over 80 years old. According to recent research (2018), in 2016, 6.1 million (95% uncertainty interval (UI) 5.0–7.3) individuals had Parkinson’s disease globally, compared with 2.5 million (2.0–3.0) in 1990. The pandemic-like spreading of PD is considered a slow-moving disaster. Most recent studies indicated the possible role of an altered microbiome, dysbiosis, in the development of PD, which occurs long before the clinical diagnosis of PD. Antibiotics are considered as major disruptors of the intestinal flora and we have hypothesized that, as different classes of antibiotics might induce different dysbiosis, certain classes of antibiotics could trigger the PD-related dysbiosis as well. Comparative analyses were performed between the average yearly antibiotic consumption of 30 European countries (1997–2016) and the PD prevalence database (estimated for 2016). We divided the time frame of antibiotic consumption of 1997–2016 into four subsections to estimate the possible time lapse between antibiotic exposure and the prevalence, prevalence change, and PD-related death rates estimated for 2016. Our results indicated that countries with high consumption of narrow-spectrum penicillin experienced a higher increase in PD prevalence than the others. Countries reporting a decline in PD from 1990 to 2016 demonstrated a reduction in the consumption of narrow-spectrum penicillin in this period.

The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997–2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with “augmenting” properties and with less consumption of antibiotics with “inhibitory” properties.

Background/Aim: With a prevalence of 50-300 per 100,000 people, about 2.3 million people are estimated to live with multiple sclerosis (MS) globally. The role of antibiotics in the development, or prevention of MS is controversial. We aimed to elucidate the association between antibiotic consumption and MS. Patients and Methods: Pearson statistical comparisons were performed between the annual average antibiotic consumption patterns expressed in Defined Daily Dose/1,000 inhabitants/Day of the antibiotic consumption for the years of 1997-2018 in 30 European countries, with the respective prevalence of MS estimated for 2016. Results: A positive correlation (promoting effect) has been observed between narrow spectrum penicillin (r=0.636) and tetracycline (r=0.412) consumption with MS prevalence. Conclusion: Countries, with high consumption of narrow spectrum penicillin and tetracycline, experience a higher prevalence of MS than other countries.

Several publications have raised the issue that the development of diabetes precedes the alteration of the microbiome (dysbiosis) and the role of environmental factors. Antibiotic use induces dysbiosis, and we wanted to estimate the associations between the consumption of antibiotics and the prevalence of diabetes (both types 1 and 2; T1D and T2D, respectively) in European countries. If such an association exists, the dominant use antibiotic classes might be reflected in the prevalence rates of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes estimated for 2019 and featured in the Diabetes Atlas and the average yearly consumption of antibiotic classes between 2010 and 2109, calculated from the European Centre for Disease Prevention and Control (ECDC) yearly reports on antibiotic consumption in Europe. Pearson’s correlation and variance analyses were used to estimate the possible relationship. Strong positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A: p = 0.001) and the narrow-spectrum penicillin (J01CE: p = 0.006; CF: p = 0.018). A strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase-resistant penicillin (J01CR: p = 0.003), macrolide (J01F: p = 0.008), and quinolone (J01M: p = 0.001). T2D showed significant positive associations with cephalosporin (J01D: p = 0.048) and quinolone (J01M: p = 0.025), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA: p = 0.067). Countries showing the highest prevalence rates of diabetes (top 10) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (top 10), as indicated by variance analysis. Countries with high prevalence rates of T1D showed high consumption of tetracycline (p = 0.015) and narrow-spectrum, beta-lactamase sensitive penicillin (p = 0.008) and low consumption of “inhibitor” antibiotics [broad-spectrum, beta-lactamase-resistant, combination penicillin (p = 0.005); cephalosporin (p = 0.036); and quinolone (p = 0.003)]. Countries with high prevalence rates of T2D consumed more cephalosporin (p = 0.084) and quinolone (p = 0.054) and less broad-spectrum, beta-lactamase-sensitive penicillin (p = 0.012) than did other countries. The development of diabetes-related dysbiosis might be related to the higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics, those showing negative (inhibitory) associations. These groups of antibiotics are different in T1D and T2D.

Clinical observations indicated a higher rate of obesity among children who received antibiotics at early ages. Experimental studies supported the role of the modified gut microbiome in the development of obesity as well. For identifying antibiotic classes that might promote or inhibit obesity-related dysbiosis, a database of the average yearly antibiotic consumption (2008–2018) has been developed using the European Center for Disease Prevention and Control (ECDC) yearly reports of antibiotic consumption in the community for the major antibiotic classes in 30 European countries, which were compared to the childhood and adult obesity prevalence featured in the Obesity Atlas. Pearson’s chi-square test was applied to estimate positive/negative correlations between antibiotic consumption and obesity. One-way ANOVA has been applied to test the differences in antibiotic consumption between groups, and logistic regression analysis was performed to determine the odds ratios (OR) of antibiotic consumption for obesity. Strong, positive associations were estimated between childhood obesity and the total consumption of systemic antibiotics, broad-spectrum, beta-lactamase-resistant penicillin, cephalosporin, and quinolone, and a negative correlation was found with the consumption of tetracycline, broad-spectrum, beta-lactamase-sensitive penicillin, and narrow-spectrum, beta-lactamase-sensitive penicillin. Our observation indicated that the “growth-promoting effect” of the consumption of certain antibiotic classes might be identified as a possible etiology in the development of obesity and might be the explanation for the obesity “pandemic”.