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Parkinson’s disease is associated with gastrointestinal (GI) dysfunction, including constipation symptoms and abnormal intestinal permeability and inflammation. A Mediterranean diet (MediDiet) may aid in disease management. This parallel, randomized, controlled trial in people with Parkinson’s (PwP) and constipation symptoms compared a MediDiet against standard of care on change in constipation symptoms, dietary intake, and fecal zonulin and calprotectin concentrations as markers of intestinal permeability and inflammation, respectively. Participants were randomized to either standard of care for constipation (control; n = 17, 65.1 ± 2.2 years) or a MediDiet plus standard of care (n = 19, 68.8 ± 1.4 years) for 8 weeks. Constipation scores decreased with both interventions (p < 0.01), but changes from baseline were not different between groups (MediDiet, −0.5 [−1.0, 0]; control, −0.8 [−1.0, 0.2]; median [25th, 75th]; p = 0.60). The MediDiet group had a higher intake of dietary fiber at week 4 than the control group (13.1 ± 0.7 g/1000 kcal vs. 9.8 ± 0.7 g/1000 kcal; p < 0.001). No differences in fecal zonulin were observed between groups (p = 0.33); however, fecal calprotectin tended to be lower in the MediDiet group at week 8 (45.8 ± 15.1 µg/g vs. 93.9 ± 26.8 µg/g; p = 0.05). The MediDiet and standard interventions reduced constipation symptoms; however, the MediDiet provided additional benefit of increased dietary fiber intake and less intestinal inflammation.

Abstract Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention.

Abstract Objective We present 16s rRNA gene sequencing (V1-V2 region) and sample data from a pilot observational cohort study to describe the gut microbiota dynamics of subjects with latent tuberculosis infection (LTBI) treated with daily 600 mg rifampicin for four months (4R) or a weekly dose of 900 mg combination of rifapentine and isoniazid for three months (3HP). Our objectives were to (1) document changes to the gut microbiota immediately following exposure to the rifamycins and (2) document recovery to baseline two months after treatment completion. Data description We enrolled six subjects with subjects with LTBI and prospectively followed them for 5–6 months. Each subject provided stool samples before, during, and two months after treatment. Six healthy controls were sampled in parallel with the patients with LTBIs. We report amplicon sequence variants (ASVs) and taxonomic assignments for 60 stool samples. Additionally, we provide access to the raw amplicon sequences, and subject responses to questionnaires about their diet, medication, and lifestyle changes over the study follow-up period. Furthermore, we provide the concentration of the parent and partially active rifamycin metabolite concentrations measured validated LC-MS-MS assays of phosphate buffer washes of the stool samples collected from the LTBI participants. This comprehensive dataset is a valuable resource for future systematic reviews and meta-analyses of the impact of LTBI therapy on the gut microbiota.

The gut brain axis (GBA), a bidirectional communication pathway has often been linked to health and disease, and gut microbiota (GM), a key component of this pathway shown to be altered in Parkinson’s disease (PD), are suggested to contribute to the pathogenesis of PD. There are few studies that report the impact of oral medication therapy on GM, however, there are even fewer studies that discuss the impact of other treatments such as device assisted therapies (DAT) including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel infusion (LCIG) and photobiomodulation (PBM) and how these might impact GM. Here, we review the literature and summarize findings of the potential contributions of GM to the heterogenous clinical response to pharmaceutical therapies among individuals with PD. We also discuss the potential interactions between the GM and DATs such as DBS and LCIG and present evidence for alterations in GM in response to DATs. Given the complexity and highly individual nature of the GM of patients with PD and the potential influence that other external factors such as diet, lifestyle, medications, stage of the disease and other comorbidities, further investigations into the response of GM to therapies are worthy of future study in prospective, controlled trials as well as medication naïve individuals. Such detailed studies will help us further comprehend the relationship between GM in PD patients, and will help investigate the potential of targeting GM associated changes as a treatment avenue for PD.

Polyphenol-rich cranberry extracts decrease intestinal inflammation, alter gut microbiota, and decrease intestinal permeability in obese mice, but the effect has not been investigated in adults who are obese. The purpose of this randomized double-blind, cross-over feeding study in obese (BMI = 37.4 ± 1.2 kg/m2) but otherwise healthy adults (n = 36) 35.4 ± 1.3 years was to determine the effects of consuming 480 mL of a high polyphenolic cranberry or control beverage daily for 2 weeks on gastrointestinal permeability, markers of inflammation and immune function, and gut microbiota. An acute aspirin challenge was administered prior to assessing intestinal permeability to determine resistance to barrier function compromise. The cranberry beverage did not affect markers of gastrointestinal permeability, inflammation, or immune function. However, fecal Faecalibacterium prausnitzii and Eggerthella lenta increased with consumption of the cranberry beverage. Data suggest that the intervention impacted bacterial communities. A longer intervention may be required to observe beneficial effects on inflammation and gastrointestinal barrier function.

Parkinson’s disease is a chronic neurodegenerative disease characterized by the accumulation of misfolded alpha-synuclein protein (Lewy bodies) in dopaminergic neurons of the substantia nigra and other related circuitry, which contribute to the development of both motor (bradykinesia, tremors, stiffness, abnormal gait) and non-motor symptoms (gastrointestinal issues, urinogenital complications, olfaction dysfunction, cognitive impairment). Despite tremendous progress in the field, the exact pathways and mechanisms responsible for the initiation and progression of this disease remain unclear. However, recent research suggests a potential relationship between the commensal gut bacteria and the brain capable of influencing neurodevelopment, brain function and health. This bidirectional communication is often referred to as the microbiome–gut–brain axis. Accumulating evidence suggests that the onset of non-motor symptoms, such as gastrointestinal manifestations, often precede the onset of motor symptoms and disease diagnosis, lending support to the potential role that the microbiome–gut–brain axis might play in the underlying pathological mechanisms of Parkinson’s disease. This review will provide an overview of and critically discuss the current knowledge of the relationship between the gut microbiota and Parkinson’s disease. We will discuss the role of α-synuclein in non-motor disease pathology, proposed pathways constituting the connection between the gut microbiome and the brain, existing evidence related to pre- and probiotic interventions. Finally, we will highlight the potential opportunity for the development of novel preventative measures and therapeutic options that could target the microbiome–gut–brain axis in the context of Parkinson’s disease.

Introduction: Non-motor symptoms of Parkinson's disease (PD) such as gastrointestinal (GI) dysfunction are common, yet little is known about how modifying dietary intake impacts PD symptoms. The aim of this study in individuals with PD was to determine whether a Mediterranean diet intervention is feasible and affects GI function, intestinal permeability and fecal microbial communities.Methods: A single-arm, 5-week Mediterranean diet intervention study was conducted in eight people with PD. Daily and weekly questionnaires were administered to determine changes in GI symptoms. Urine and stool samples were collected at baseline and after 5 weeks to assess intestinal permeability and fecal microbial communities. Additionally, live-in partners of the participants with PD were matched as controls (n = 8) for baseline urine and stool samples.Results: Participants with PD increased intake of Mediterranean diet based on adherence scores from baseline to week 5 (4.4 ± 0.6 vs. 11.9 ± 0.7; P < 0.01 with >10 representing good adherence), which was linked with weight loss (77.4 kg vs. 74.9 kg, P = 0.01). Constipation syndrome scores decreased after 5 weeks (2.3 ± 0.5 vs. 1.5 ± 0.3; P = 0.04). Bilophila, was higher at baseline in PD (0.6 ± 0.1% vs. 0.2 ± 0.1% P = 0.02) and slightly decreased after the diet intervention (0.5 ± 0.1%; P = 0.01). Interestingly, the proportion of Roseburia was significantly lower in PD compared to controls (0.6 ± 0.2% vs. 1.6 ± 0.3%; P = 0.02) and increased at week 5 (0.9 ± 0.2%; P < 0.01). No differences were observed for markers of intestinal permeability between the control and PD groups or post-intervention.Conclusions: Short-term Mediterranean diet adherence is feasible in participants with PD; correlated with weight loss, improved constipation, and modified gut microbiota.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03851861.

Abstract Background Dried fruits, such as raisins, contain phytochemicals and dietary fibers that contribute to maintaining health, potentially at least partially through modification in gut microbiota composition and activities. However, the effects of raisin consumption on gut microbiota have not previously been thoroughly investigated in humans. Therefore, the objective of this study was to determine how adding three servings of sun dried raisin/day to the diet of healthy volunteers affects gut microbiota composition. Methods A 14-day exploratory feeding study was conducted with thirteen healthy individuals between the ages of 18 and 59 years. Participants consumed three servings (28.3 g each) of sun dried raisins daily. Fecal samples were collected prior to raisin consumption (baseline) and after the addition of raisins to the diet (on days 7 and 14). To determine the effects of raisin intake, fecal microbiota composition before and after raisin consumption was characterized for each participant by 16S rRNA gene sequencing. Results Overall microbiota diversity was not significantly affected by adding raisins to the diet. However, upon addition of raisins to the diet specific OTUs matching Faecalibacterium prausnitzii, Bacteroidetes sp. and Ruminococcus sp. increased in prevalence while OTUs closest to Klebsiella sp., Prevotella sp. and Bifidobacterium spp. decreased. Conclusion Our findings suggest that adding raisins to the diet can affect the prevalence of specific bacterial taxa. Potential health benefits of the observed microbiota changes should be determined in future studies in populations for which specific health outcomes can be targeted. Trial registration http://www.clinicaltrials.gov; Identifier: NCT02713165.

The microbiome-gut-brain axis, or the various interactions between the gut microbiome and the brain, has been of recent interest in the context of precision medicine research for a variety of disease states. Persons living with human immunodeficiency virus (PLWH) experience higher degrees of neurocognitive decline than the general population, correlating with a disruption of the normal gut microbiome composition (i.e. dysbiosis). While the nature of this correlation remains to be determined, there is the potential that the microbiome-gut-brain axis contributes to the progression of this disease. Previous research has established that the pathology associated with HIV induces alterations in the composition of gut microbiome, including a shift from Bacteroides to Prevotella dominance, and compromises gut barrier integrity, which may promote microbial translocation and consequent systemic inflammation and exacerbation of neuroinflammation. Further, though the use of antiretroviral therapy has been found to partially counteract HIV-related dysbiosis, it may also induce its own dysbiosis patterns, presenting a unique challenge for this research.More recent research has suggested the gut microbiome as a target for therapeutic interventions to improve symptoms associated with a variety of disease states, including HIV. Early findings are promising and warrant further research regarding the gut microbiome as a potential modifiable factor to improve health outcomes for PLWH. This review will discuss the current knowledge concerning the neuropathogenesis of HIV in the brain, role of the gut microbiome in neuroinflammation, and the relationship between HIV-status and the gut microbiome, followed by a conclusion that synthesizes this information within the context of the microbiome-gut-brain axis among PLWH. This review will also highlight the limitations of existing studies and propose future directions of this research.

Background: We have previously reported that the addition of resistant maltodextrin (RMD), a fermentable functional fiber, to the diet increases fecal weight as well as the amount of fecal bifidobacteria. Here, we report on the targeted analysis of changes in potentially beneficial gut bacteria associated with the intervention. Objective: The primary objective of this study was to determine the effect of adding 0, 15 and 25 g RMD to the diets of healthy free-living adults on potentially beneficial gut bacteria. Methods: We expanded on our previously reported microbiota analysis in a double-blind, placebo-controlled feeding study (NCT02733263) by performing additional qPCR analyses targeting fecal lactic acid bacteria (LAB), Akkermansia muciniphila, Faecalibacterium prausnitzii and Fusicatenibacter saccharivorans in samples from 49 participants. Results: RMD resulted in an approximately two-fold increase in fecal Fusicatenibacter saccharivorans (p = 0.024 for 15 g/day RMD and p = 0.017 for 25 g/day RMD). For Akkermansia muciniphila and Faecalibacterium prausnitzii, we obtained borderline evidence that showed increased amounts in participants that had low baseline levels of these bacteria (p < 0.1 for 25 g/day RMD). We did not detect any effects of RMD on LAB. Conclusions: RMD supplementation in healthy individuals increases Fusicatenibacter saccharivorans. Albeit to a lesser extent, RMD at the higher intake level may also increase Akkermansia muciniphila and Faecalibacterium prausnitzii in individuals with low baseline levels of those two species. Potential benefits associated with these microbiota changes remain to be established in studies with quantifiable health-related endpoints.

ABSTRACT The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the “metavirome” of four populations of Aedes aegypti mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in A. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. IMPORTANCE Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks.

Elevated inflammatory cytokines and chronic pain are associated with shorter leukocyte telomere length (LTL), a measure of cellular aging. Micronutrients, such as 25-hydroxyvitamin D (vitamin D) and omega 3, have anti-inflammatory properties. Little is known regarding the relationships between vitamin D, omega 6:3 ratio, LTL, inflammation, and chronic pain. We investigate associations between vitamin D, omega 6:3 ratio, LTL, and C-reactive protein (CRP) in people living with/without chronic pain overall and stratified by chronic pain status. A cross-sectional analysis of 402 individuals (63% women, 79.5% with chronic pain) was completed. Demographic and health information was collected. Chronic pain was assessed as pain experienced for at least three months. LTL was measured in genomic DNA isolated from blood leukocytes, and micronutrients and CRP were measured in serum samples. Data were analyzed with general linear regression. Although an association between the continuous micronutrients and LTL was not observed, a positive association between omega 6:3 ratio and CRP was detected. In individuals with chronic pain, based on clinical categories, significant associations between vitamin D, omega 6:3 ratio, and CRP were observed. Findings highlight the complex relationships between anti-inflammatory micronutrients, inflammation, cellular aging, and chronic pain.

The aim was to assess whether citrus pomace increases stool frequency in healthy adults. In this randomised, blinded, controlled trial, healthy adults (62% females) received a beverage containing pomace (473 mL/day, providing 10 g fibre/day, n = 111) or control (n = 110) for 3 weeks. Stool frequency, Bristol Stool Form Scale (BSFS), and Gastrointestinal Symptom Rating Scale (GSRS) scores were self-assessed. 24-h diet recalls were completed once/week. Stool microbiota were analysed by 16S rRNA sequencing and qPCR. Mean total daily fibre intake was higher with pomace vs. control (P

We performed a study to (i) investigate efficacy of an Escherichia coli/Salmonella spp./Listeria monocytogenes-targeting bacteriophage cocktail (tentatively named F.O.P.) to reduce a human pathogenic E. coli strain O157:H7 in experimentally infected mice, and (ii) determine how bacteriophages impact the normal gut microbiota when compared with antibiotic therapy. A total of 85 mice were inoculated with E. coli O157:H7 strain Ec231 [nalidixic acid resistant (NalAcR)] via oral gavage, and were randomized into six groups separated into three categories: 1st category received PBS or No phage/No PBS (control), 2nd category received either F.O.P., F.O.P. at 1:10 dilution, or only the E. coli phage component of F.O.P. (EcoShield PXTM), and 3rd category received the antibiotic ampicillin. All therapies were administered twice daily for four consecutive days including before and after bacterial challenge; except ampicillin which was administered only before and after bacterial challenge on day 0. Fecal samples were collected at Days 0, 1, 2, 3, 5, and 10. Samples were homogenized and plated on LB plates supplemented with NalAc to determine viable Ec231 counts. Body weights were measured at every fecal sample collection point. qPCR was performed using specific E. coli O157:H7 primers to quantify the number of E. coli O157:H7 genome copies. Microbiota community profiles were analyzed using Denature Gradient Gel Electrophoresis (DGGE) and 16S rRNA sequencing. F.O.P. significantly (P < 0.05) reduced E. coli O157:H7 pathogen counts by 54%. Ampicillin therapy significantly (P < 0.05) reduced E. coli O157:H7 pathogen counts by 79%. Greater initial weight-loss occurred in mice treated with ampicillin (−5.44%) compared to other treatment groups. No notable changes in the gut microbiota profiles were observed for control and F.O.P. groups. In contrast, the antibiotic group displayed noticeable distortion of the gut microbiota composition, only partially returning to normal by Day 10. In conclusion, we found that F.O.P. administration was effective in reducing viable E. coli O157:H7 in infected mice with a similar efficacy to ampicillin therapy. However, the F.O.P. bacteriophage preparation had less impact on the gut microbiota compared to ampicillin.

Although the over-use of antibiotics during food animal production is a potential driver of antimicrobial resistant microorganisms (ARMs), a high prevalence of cefotaxime resistant bacteria (CRB) has been observed in grazing animals raised without antibiotic supplementation. In this cross-sectional study, the prevalence and concentration of CRB in beef cattle on grazing farms were investigated. Fecal samples from the recto-anal junction of cattle (n = 840) and environmental samples (n = 258) were collected from 17 farms in North and Central Florida in the United States, and a survey of farm characteristics, animal husbandry practices, and antibiotic usage was conducted. CRB were detected in fecal samples from 47.4% of all cattle, with the prevalence ranging from 21.1 to 87.5% on farms, and significantly higher (P < 0.001) in calves compared to adult cows (54.1 vs. 41.8%). Environmental samples had a higher prevalence than fecal samples (P < 0.001), with CRB detected in 88.6% of water, 98.7% of soil, and 95.7% of forage samples. Compared to the concentration (log CFU/g) of CRB in fecal samples (2.95, 95% CI: 2.89, 3.02), the concentration of CRB was higher (P < 0.001) in soil and forage samples (5.37, 95% CI: 5.16, 5.57) and lower (P < 0.001) in water samples (1.08, 95% CI: 0.82, 1.36). Soil microbiota from farms with high prevalence of CRB clustered closer together and the proportion of Phylum Proteobacteria was higher on farms with high prevalence of CRB resistance. Large farming operations were associated with a 58% higher likelihood of CRB detection in fecal samples. Regular cleaning of drinking troughs and the addition of ionophores to feed were associated with CRB reduction in fecal samples. Taken together, the widespread of CRB into both cattle seldom treated with cephalosporin antibiotics and the surrounding environment suggests the environment is a natural source of antimicrobial resistance in beef cattle.

ObjectiveTo determine the differences in preterm infants' stool microbiota considering the use of exclusive own mother's milk and formula in different proportions in the first 28 days of life.MethodsThe study included newborns with GA ≤ 32 weeks divided in 5 group according the feeding regimen: 7 exclusive own mother's milk, 8 exclusive preterm formula, 16 mixed feeding with >70% own mother's milk, 16 mixed feeding with >70% preterm formula, and 15 mixed 50% own mother's milk and preterm formula. Exclusion criteria: congenital infections, congenital malformations and newborns of drug addicted mothers. Stools were collected weekly during the first 28 days. Microbial DNA extraction, 16S rRNA amplification and sequencing were performed.ResultsAll groups were similar in perinatal and neonatal data. There were significant differences in microbial community among treatments. Approximately 37% of the variation in distance between microbial communities was explained by use of exclusive own mother´s milk only compared to other diets. The diet composed by exclusive own mother´s milk allowed for greater microbial richness (average of 85 OTUs) while diets based on preferably formula, exclusive formula, preferably maternal milk, and mixed of formula and maternal milk presented an average of 9, 29, 23, and 25 OTUs respectively. The mean proportion of the genus Escherichia and Clostridium was always greater in those containing formula than in the those with maternal milk only.ConclusionsFecal microbiota in the neonatal period of preterm infants fed with exclusive own mother's milk presented increased richness and differences in microbial composition from those fed with different proportions of formula.

Despite increased efforts, the diverse etiologies of Necrotizing Enterocolitis (NEC) have remained largely elusive. Clinical predictors of NEC remain ill-defined and currently lack sufficient specificity. The development of a thorough understanding of initial gut microbiota colonization pattern in preterm infants might help to improve early detection or prediction of NEC and its associated morbidities. Here we compared the fecal microbiota successions, microbial diversity, abundance and structure of newborns that developed NEC with preterm controls. A 16S rRNA based microbiota analysis was conducted in a total of 132 fecal samples that included the first stool (meconium) up until the 5th week of life or NEC diagnosis from 40 preterm babies (29 controls and 11 NEC cases). A single phylotype matching closest to the Enterobacteriaceae family correlated strongly with NEC. In DNA from the sample with the greatest abundance of this phylotype additional shotgun metagenomic sequencing revealed Citrobacter koseri and Klebsiella pneumoniae as the dominating taxa. These two taxa might represent suitable microbial biomarker targets for early diagnosis of NEC. In NEC cases, we further detected lower microbial diversity and an abnormal succession of the microbial community before NEC diagnosis. Finally, we also detected a disruption in anaerobic microorganisms in the co-occurrence network of meconium samples from NEC cases. Our data suggest that a strong dominance of Citrobacter koseri and/or Klebsiella pneumoniae, low diversity, low abundance of Lactobacillus, as well as an altered microbial-network structure during the first days of life, correlate with NEC risk in preterm infants. Confirmation of these findings in other hospitals might facilitate the development of a microbiota based screening approach for early detection of NEC.

The rapid development of sequencing technology has led to an explosive accumulation of genomic sequence data. Clustering is often the first step to perform in sequence analysis, and hierarchical clustering is one of the most commonly used approaches for this purpose. However, it is currently computationally expensive to perform hierarchical clustering of extremely large sequence datasets due to its quadratic time and space complexities. In this paper we developed a new algorithm called ESPRIT-Forest for parallel hierarchical clustering of sequences. The algorithm achieves subquadratic time and space complexity and maintains a high clustering accuracy comparable to the standard method. The basic idea is to organize sequences into a pseudo-metric based partitioning tree for sub-linear time searching of nearest neighbors, and then use a new multiple-pair merging criterion to construct clusters in parallel using multiple threads. The new algorithm was tested on the human microbiome project (HMP) dataset, currently one of the largest published microbial 16S rRNA sequence dataset. Our experiment demonstrated that with the power of parallel computing it is now compu- tationally feasible to perform hierarchical clustering analysis of tens of millions of sequences. The software is available at http://www.acsu.buffalo.edu/∼yijunsun/lab/ESPRIT-Forest.html.

BACKGROUND:Administering intravenous antibiotics during labor to women at risk for transmitting Group B Streptococcus (GBS) can prevent infections in newborns. However, the impact of intrapartum antibiotic prophylaxis on mothers' microbial community composition is largely unknown. We compared vaginal microbial composition in pregnant women experiencing preterm birth at ≤ 32 weeks gestation that received intrapartum antibiotic prophylaxis with that in controls. METHODS:Microbiota in vaginal swabs collected shortly before delivery from GBS positive women that received penicillin intravenously during labor or after premature rupture of membranes was compared to controls. Microbiota was analyzed by 16S rRNA sequencing using the PGM Ion Torrent to determine the effects of penicillin use during hospitalization and GBS status on its composition. RESULTS:Penicillin administration was associated with an altered vaginal microbial community composition characterized by increased microbial diversity. Lactobacillus sp. contributed only 13.1% of the total community in the women that received penicillin compared to 88.1% in the controls. Streptococcus sp. were present in higher abundance in GBS positive woman compared to controls, with 60% of the total vaginal microbiota in severe cases identified as Streptococcus sp. CONCLUSIONS:Vaginal communities of healthy pregnant women were dominated by Lactobacillus sp. and contained low diversity, while Group B Streptococcus positive women receiving intrapartum antibiotic prophylaxis had a modified vaginal microbiota composition with low abundance of Lactobacillus but higher microbial diversity.

Phenylketonuria (PKU) is an inborn error of metabolism associated with high blood levels of phenylalanine (Phe). A Phe-restricted diet supplemented with L-amino acids is the main treatment strategy for this disease; if started early, most neurological abnormalities can be prevented. The healthy human gut contains trillions of commensal bacteria, often referred to as the gut microbiota. The composition of the gut microbiota is known to be modulated by environmental factors, including diet. In this study, we compared the gut microbiota of 8 PKU patients on Phe-restricted dietary treatment with that of 10 healthy individuals. The microbiota were characterized by 16S rRNA sequencing using the Ion Torrent™ platform. The most dominant phyla detected in both groups were Bacteroidetes and Firmicutes. PKU patients showed reduced abundance of the Clostridiaceae, Erysipelotrichaceae, and Lachnospiraceae families, Clostridiales class, Coprococcus, Dorea, Lachnospira, Odoribacter, Ruminococcus and Veillonella genera, and enrichment of Prevotella, Akkermansia, and Peptostreptococcaceae. Microbial function prediction suggested significant differences in starch/glucose and amino acid metabolism between PKU patients and controls. Together, our results suggest the presence of distinct taxonomic groups within the gut microbiome of PKU patients, which may be modulated by their plasma Phe concentration. Whether our findings represent an effect of the disease itself, or a consequence of the modified diet is unclear.

Abstract Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.

Abstract The use of proteins as targeting agents often requires their chemical modification for their efficient attachment to a given surface. However, no control over the protein integrity and functionality has been demonstrated to date. Chemical over‐modification causes the loss of the native structure of the protein and thus limits its targeting efficiency. To preserve structural integrity, a minimal modification strategy of proteins is developed while maintaining their functionality. Apolipoprotein A1 (ApoA1) and liposomes are utilized as a nanocarrier platform. Monitoring NHS ester chemistry by time‐of‐flight mass spectrometry experiments, the proposed functionalization route allows the effective chemical coupling of the minimally modified ApoA1 to the surface of the liposomes via a click chemistry reaction. The stability of the modified ApoA1 is ensured by analyzing the secondary structure by circular dichroism spectroscopy and the corresponding melting point by nano differential scanning fluorimetry. Furthermore, ApoA1 attachment to the liposomes is confirmed by flow cytometry experiments. The procedure presented in this study has the potential to be easily transferred to other proteins while introducing only minimally necessary chemical modifications to be covalently attached to different drug delivery platforms. This can help to improve their targeting efficiency for future biomedical applications.

Abstract Nanocapsules enable multicomponent encapsulation of therapeutic cargoes with high encapsulation content and efficiency, which is vital for cancer immunotherapy. In the past, chemical crosslinking is used to synthesize nanocapsules, which can impede the regulatory approval process. Therefore, a new class of protein nanocapsules is developed by eliminating the need for chemical crosslinking by utilizing protein denaturation through a process that is referred to as “baking at the droplet interface”. Such protein nanocapsules with antigens incorporated in the shell and a combination of encapsulated drugs showed an enhancement in the immune response of cells.

Abstract After decades where human spaceflight missions have been reserved to low Earth orbit, recent years have seen mission proposals and even implemented plans, e.g. with the mission Artemis I, for returning to the lunar surface. SpaceX has published over various media (e.g., its official website, conference presentations, user manual) conceptual information for its reusable Starship to enable human exploration missions to the Martian surface by the end of the decade. The technological and human challenges associated with these plans are daunting. Such a mission at that distance would require excellent system reliability and in-situ-resource utilization on a grand scale, e.g. to produce propellant. The plans contain little details however and have not yet been reviewed concerning their feasibility. In this paper we show significant technological gaps in these plans. Based on estimates and extrapolated data, a mass model as needed to fulfill SpaceX’s plans could not be reproduced and the subsequent trajectory optimization showed that the current plans do not yield a return flight opportunity, due to a too large system mass. Furthermore, significant gaps exist in relevant technologies, e.g. power supply for the Martian surface. It is unlikely that these gaps can be closed until the end of the decade. We recommend several remedies, e.g. stronger international participation to distribute technology development and thus improve feasibility. Overall, with the limited information published by SpaceX about its system and mission scenario and extrapolation from us to fill information gaps, we were not able to find a feasible Mars mission scenario using Starship, even when assuming optimal conditions such as 100% recovery rate of crew consumables during flight.

Abstract The influence of a protein corona on the uptake of nanoparticles in cells has been demonstrated in various publications over the last years. Extracellular vesicles (EVs), can be seen as natural nanoparticles. However, EVs are produced under different cell culture conditions and little is known about the protein corona forming on EVs and its influence on their uptake by target cells. Here, we use a proteomic approach in order to analyze the protein composition of the EVs themselves and the protein composition of a human blood plasma protein corona around EVs. Moreover, we analyze the influence of the protein corona on EV uptake into human monocytes and compare it with the influence on the uptake of engineered liposomes. We show that the presence of a protein corona increases the uptake of EVs in human monocytes. While for liposomes this seems to be triggered by the presence of immunoglobulins in the protein corona, for EVs blocking the Fc receptors on monocytes did not show an influence of uptake. Therefore, other mechanisms of docking to the cell membrane and uptake are most like involved, demonstrating a clear difference between EVs and liposomes as technically produced nanocarriers.