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The composition of the gut microbiome is linked to multiple diseases, including Parkinson’s disease (PD). Bacteria producing short-chain fatty acids (SCFAs) and fecal SCFA concentrations are reduced in PD. SCFAs exert various beneficial functions in humans. In the interventional, monocentric, open-label clinical trial RESISTA-PD (NCT02784145) we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch (RS). We enrolled 87 subjects in three study-arms: 32 PD patients receiving RS (PD + RS), 30 control subjects receiving RS, and 25 PD patients receiving solely dietary instructions. We performed paired-end 100 base pair length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 GB. RS was well-tolerated. In PD + RS, fecal butyrate concentrations increased significantly and fecal calprotectin concentrations dropped significantly after 8 weeks of RS. Clinically, we observed a reduction in non-motor symptoms load in PD + RS. The reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups, including bacteria producing SCFAs. Reference-free analysis suggested punctual, yet pronounced differences in the metagenomic signature in PD + RS. RESISTA-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in PD. The stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations calls for long-term studies, also investigating whether RS is able to modify the clinical course of PD.

Parkinson’s disease (PD) is one of the most common neurodegenerative disease, and is so far not considered curable. PD patients suffer from several motor and non-motor symptoms, including gastrointestinal dysfunctions and alterations of the enteric nervous system. Constipation and additional intestinal affections can precede the classical motor symptoms by several years. Recently, we reported effects of PD and related medications on the faecal bacterial community of 34 German PD patients and 25 age-matched controls. Here, we used the same collective and analysed the V6 and V7 hypervariable region of PCR-amplified, eukaryotic 18S rRNA genes using an Illumina MiSeq platform. In all, 53% (18) of the PD samples and 72% (18) of the control samples yielded sufficient amplicons for downstream community analyses. The PD samples showed a significantly lower alpha and a different beta eukaryotic diversity than the controls. Most strikingly, we observed a significantly higher relative abundance of sequence affiliated with the Geotrichum genus in the PD samples (39.7%), when compared to the control samples (0.05%). In addition, we observed lower relative abundances of sequences affiliated with Aspergillus/Penicillium, Charophyta/Linum, unidentified Opisthokonta and three genera of minor abundant zooflagellates in the PD samples. Our data add knowledge to the small body of data about the eukaryotic microbiota of PD patients and suggest a potential association of certain gut eukaryotes and PD.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. PD patients suffer from gastrointestinal dysfunctions and alterations of the autonomous nervous system, especially its part in the gut wall, i.e., the enteric nervous system (ENS). Such alterations and functional gastrointestinal deficits often occur years before the classical clinical symptoms of PD appear. Until now, only little is known about PD-associated changes in gut microbiota composition and their potential implication in PD development. In order to increase knowledge in this field, fecal samples of 34 PD patients and 25 healthy, age-matched control persons were investigated. Here, the V4 and V5 hypervariable region of bacterial 16S rRNA genes was PCR-amplified and sequenced using an Ion Torrent PGM platform. Within the PD group, we observed a relative decrease in bacterial taxa which are linked to health-promoting, anti-inflammatory, neuroprotective or other beneficial effects on the epithelial barrier, such as Faecalibacterium and Fusicatenibacter. Both taxa were lowered in PD patients with elevated levels of the fecal inflammation marker calprotectin. In addition, we observed an increase in shares of the Clostridiales family XI and their affiliated members in these samples. Finally, we found that the relative abundances of the bacterial genera Peptoniphilus, Finegoldia, Faecalibacterium Fusicatenibacter, Anaerococcus, Bifidobacterium, Enterococcus, and Ruminococcus were significantly influenced by medication with L-dopa and entacapone, respectively. Our data confirm previously reported effects of COMT inhibitors on the fecal microbiota of PD patients and suggest a possible effect of L-dopa medication on the relative abundance of several bacterial genera.

Cardiac dysautonomia is a potentially life-threatening complication of Guillain-Barré syndrome (GBS). Proper and prompt recognition of patients at risk and subsequent intensive care unit (ICU) monitoring are mandatory to prevent fatal outcome. Eyeball pressure testing (EP) has been suggested as an easy applicable bedside test for vagal overreactivity in GBS and thus identifying patients at risk. Yet, there is only sparse follow-up data concerning the course of EP findings in GBS. We report a 25 years-old male patient with GBS who underwent consecutive EP (n = 11) during his ICU stay over a period of 11 weeks. The series of tests performed in this patient (and corresponding clinical events) show that EP data might represent an approximation of vagal dysfunction and vagal recovery in GBS. Interestingly, we observed a much longer duration of pathological EP compared to a previous report. The tenacious cardiac dysautonomia in this patient necessitated long-term application of a transvenous temporary pacemaker.

Background. Multiple Sclerosis (MS) is primarily considered as a neuro-inflammatory CNS disease. Yet, experimental data suggest a role for gut microbiota and microbial products like short chain fatty acids (SCFA) in the pathogenesis of MS. Very recently a high-ranked publication reported beneficial effects of propionate, a SCFA, in MS patients. Based on experimental and preliminary human data, we hypothesized that not only the gut microbiota but also microbial products and fecal inflammatory markers might be altered in MS.Methods. In a pilot study, we investigated fecal markers (short chain fatty acids, calprotectin) as well as clinical markers in patients with relapsing-remitting MS (RRMS) under different therapeutic regimes and compared the results to age-matched control subjects.Results. We observed a non-significant reduction in fecal SCFA in RRMS patients compared to control subjects. Fecal calprotectin concentrations did not differ significantly between MS patients and control subjects. We observed a significant reduction in fecal SCFA concentrations in women compared to men.Conclusions. We conclude that the observed sex-associated difference in fecal SCFA concentrations might be a contributing factor in the pathogenesis of MS, especially when taking into account the female predominance in MS. We suggest investigating the role of SCFA in MS in a longitudinal study (starting in drug-naïve patients) in larger cohorts of MS patients with defined therapeutic regimes. Such a study would allow to distinguish between drug effects and disease-immanent effects and might help to identify a potentially modifiable sex-associated contributing factor in MS.Trial registration. Registered by the local Ethics Committee (Reg.Nr. 81/18, Ethikkommission der Aerztekammer des Saarlandes, Saarbruecken, Germany).

Introduction In Germany vaccination recommendations are revised annually and published by the Standing Committee on Vaccination at the Robert Koch Institute (STIKO). In 2010 the vaccination recommendations were amended to include the proposal that pregnant women in the 2nd trimester of pregnancy and pregnant women with additional underlying disease in the 1st trimester of pregnancy should be vaccinated against seasonal influenza. This paper reports on vaccination rates and the factors influencing them. Method A cross-sectional study was carried out in two level 1 perinatal centers in two different German federal states (Saarland and Rhineland-Palatinate) during the influenza seasons of 2012/2013 and 2013/2014. A total of 253 pregnant women were included in the study. Pregnant women were interviewed using a standardized, pre-tested questionnaire and asked whether they were aware of the recommendation to vaccinate against seasonal influenza and about possible factors which might influence their decision to be vaccinated. In addition, data from their vaccination certificates and pregnancy passports were evaluated. Results Overall, the records of only 19.5 % of the pregnant women showed that they had been vaccinated against influenza in pregnancy. Among the group of pregnant women who had a previous history of vaccinations against influenza the willingness to be vaccinated was high (43.3 %) and this figure was statistically significant. The vaccination rate was even higher (49.9 %) and even more statistically significant among pregnant women whose gynecologist or family physician had recommended that they should be vaccinated. In contrast, only 3.3 % of pregnant women who had not been given the recommendation to vaccinate by their physicians were vaccinated against influenza. Discussion The failure to recommend that pregnant women be vaccinated against influenza and womenʼs lack of any previous experience of influenza vaccination were the main reasons for the inadequate influenza vaccination coverage in pregnancy. Conclusion One of the key points to increase the influenza vaccination rate is to intensify the counselling of the pregnant women through the gynecologist.

Neuroinflammation is increasingly recognized as an important pathophysiological feature of neurodegenerative diseases such as Parkinson’s disease (PD). Recent evidence suggests that neuroinflammation in PD might originate in the intestine and the bidirectional communication between the central and enteric nervous system, the so-called “gut-brain axis,” has received growing attention due to its contribution to the pathogenesis of neurological disorders. Diet targets mediators of inflammation with various mechanisms and combined with dopaminergic treatment can exert various beneficial effects in PD. Food-based therapies may favorably modulate gut microbiota composition and enhance the intestinal epithelial integrity or decrease the proinflammatory response by direct effects on immune cells. Diets rich in pre- and probiotics, polyunsaturated fatty acids, phenols including flavonoids, and vitamins, such as the Mediterranean diet or a plant-based diet, may attenuate chronic inflammation and positively influence PD symptoms and even progression of the disease. Dietary strategies should be encouraged in the context of a healthy lifestyle with physical activity, which also has neuroimmune-modifying properties. Thus, diet adaptation appears to be an effective additive, nonpharmacological therapeutic strategy that can attenuate the chronic inflammation implicated in PD, potentially slow down degeneration, and thereby modify the course of the disease. PD patients should be highly encouraged to adopt corresponding lifestyle modifications, in order to improve not only PD symptoms, but also general quality of life. Future research should focus on planning larger clinical trials with dietary interventions in PD in order to obtain hard evidence for the hypothesized beneficial effects.

Parkinson's disease (PD) is an etiologically heterogeneous disorder. Experimental, clinical and epidemiological data suggest that intestinal inflammation contributes to the pathogenesis of PD. This article reviews recent literature on gut microbiota and intestinal inflammation in PD. We propose that intestinal inflammation links environmental factors (e.g. an altered gut microbiota composition) to neurodegeneration in (genetically susceptible) PD patients. In addition, there is an epidemiological and genetic overlap between PD and inflammatory bowel disease. This overlap provides an opportunity to develop new treatment strategies for at least a subgroup of PD patients.