Background and purpose: The role of the gut microbiome in the pathogenesis of Parkinson disease (PD) is under intense investigation, and the results presented are still very heterogeneous. These discrepancies arise not only from the highly heterogeneous pathology of PD, but also from widely varying methodologies at all stages of the workflow, from sampling to final statistical analysis. The aim of the present work is to harmonize the workflow across studies to reduce the methodological heterogeneity and to perform a pooled analysis to account for other sources of heterogeneity.Methods: We performed a systematic review to identify studies comparing the gut microbiota of PD patients to healthy controls. A workflow was designed to harmonize processing across all studies from bioinformatics processing to final statistical analysis using a Bayesian random‐effects meta‐analysis based on individual patient‐level data.Results: The results show that harmonizing workflows minimizes differences between statistical methods and reveals only a small set of taxa being associated with the pathogenesis of PD. Increased shares of the genera Akkermansia and Bifidobacterium and decreased shares of the genera Roseburia and Faecalibacterium were most characteristic for PD‐associated microbiota.Conclusions: Our study summarizes evidence that reduced levels of butyrate‐producing taxa in combination with possible degradation of the mucus layer by Akkermansia may promote intestinal inflammation and reduced permeability of the gut mucosal layer. This may allow potentially pathogenic metabolites to transit and enter the enteric nervous system.

Milk extracellular vesicles (mEVs) seem to be one of the main maternal messages delivery systems. Extracellular vesicles (EVs) are micro/nano-sized membrane-bound structures enclosing signaling molecules and thus acting as signal mediators between distant cells and/or tissues, exerting biological effects such as immune modulation and pro-regenerative activity. Milk is also a unique, scalable, and reliable source of EVs. Our aim was to characterize the RNA content of cow, donkey, and goat mEVs through transcriptomic analysis of mRNA and small RNA libraries. Over 10,000 transcripts and 2000 small RNAs were expressed in mEVs of each species. Among the most represented transcripts, 110 mRNAs were common between the species with cow acting as the most divergent. The most represented small RNA class was miRNA in all the species, with 10 shared miRNAs having high impact on the immune regulatory function. Functional analysis for the most abundant mRNAs shows epigenetic functions such as histone modification, telomere maintenance, and chromatin remodeling for cow; lipid catabolism, oxidative stress, and vitamin metabolism for donkey; and terms related to chemokine receptor interaction, leukocytes migration, and transcriptional regulation in response to stress for goat. For miRNA targets, shared terms emerged as the main functions for all the species: immunity modulation, protein synthesis, cellular cycle regulation, transmembrane exchanges, and ion channels. Moreover, donkey and goat showed additional terms related to epigenetic modification and DNA maintenance. Our results showed a potential mEVs immune regulatory purpose through their RNA cargo, although in vivo validation studies are necessary.

Introduction: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. Aim: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. Materials and Methods: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. Results: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1β (p = 0.529) and IL-6 (p = 0.828) in the two groups. Conclusions: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.

Over the past decades, Salmonella 4,[5],12:i:- has rapidly emerged and it is isolated with high frequency in the swine food chain. Although many studies have documented the epidemiological success of this serovar, few investigations have tried to explain this phenomenon from a genetic perspective. Here a comparative whole-genome analysis of 50 epidemiologically unrelated S. 4,[5],12:i:-, isolated in Italy from 2010-2016 was performed, characterizing them in terms of genetic elements potentially conferring resistance, tolerance and persistence characteristics. Phylogenetic analyses indicated interesting distinctions among the investigated isolates. The most striking genetic trait characterizing the analysed isolates is the widespread presence of heavy metals tolerance gene cassettes: most of the strains possess genes expected to confer resistance to copper and silver, whereas about half of the isolates also contain the mercury tolerance gene merA. A functional assay showed that these genes might be useful for preventing the toxic effects of metals, thus supporting the hypothesis that they can contribute to the success of S. 4,[5],12:i:- in farming environments. In addition, the analysis of the distribution of type II toxin-antitoxin families indicated that these elements are abundant in this serovar, suggesting that this is another factor that might favour its successful spread.

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn’s disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables “age”, “eat yogurt at least four days per week” and “eat dairy products at least 4 days per week” as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables “age”, “gender”, “eat meat at least four days per week” and “eat bread at least 4 days per week” were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour.