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Gingivitis-the inflammation of the gums-is a reversible stage of periodontal disease. It is caused by dental plaque formation due to poor oral hygiene. However, gingivitis susceptibility involves a complex set of interactions between the oral microbiome, oral metabolome and the host. In this study, we investigated the dynamics of the oral microbiome and its interactions with the salivary metabolome during experimental gingivitis in a cohort of 41 systemically healthy participants. We use Parallel Factor Analysis (PARAFAC), which is a multi-way generalization of Principal Component Analysis (PCA) that can model the variability in the response due to subjects, variables and time. Using the modelled responses, we identified microbial subcommunities with similar dynamics that connect to the magnitude of the gingivitis response. By performing high level integration of the predicted metabolic functions of the microbiome and salivary metabolome, we identified pathways of interest that describe the changing proportions of Gram-positive and Gram-negative microbiota, variation in anaerobic bacteria, biofilm formation and virulence., (© 2024. The Author(s).)

Loop-Mediated Isothermal Amplification (LAMP) technology is emerging as a rapid pathogen testing method, potentially challenging the RT-PCR "gold standard". Despite recent advancements, LAMP's widespread adoption remains limited. This study provides a comprehensive market overview and assesses future growth prospects to aid stakeholders in strategic decision-making and policy formulation. Using a dataset of 1134 LAMP patent documents, we analyzed lifecycle and geographic distribution, applicant profiles, CPC code classifications, and patent claims. Additionally, we examined clinical developments from 21 curated clinical trials, focusing on trends, geographic engagement, sponsor types, and the conditions and pathogens investigated. Our analysis highlights LAMP's potential as a promising rapid pathogen testing alternative, especially in resource-limited areas. It also reveals a gap between clinical research, which targets bacterial and parasitic diseases like malaria, leishmaniasis, and tuberculosis, and basic research and commercial efforts that prioritize viral diseases such as SARS-CoV-2 and influenza. European stakeholders emphasize the societal impact of addressing unmet needs in resource-limited areas, while American and Asian organizations focus more on research, innovation, and commercialization.

Introduction: The aim of the study was to evaluate the modulating effects of five commonly used sweetener (glucose, inulin, isomaltulose, tagatose, trehalose) containing mouth rinses on the oral microbiome., Methods: A single-centre, double-blind, parallel randomized clinical trial was performed with healthy, 18-55-year-old volunteers (N = 65), who rinsed thrice-daily for two weeks with a 10% solution of one of the allocated sweeteners. Microbiota composition of supragingival dental plaque and the tongue dorsum coating was analysed by 16S RNA gene amplicon sequencing of the V4 hypervariable region (Illumina MiSeq). As secondary outcomes, dental plaque red fluorescence and salivary pH were measured., Results: Dental plaque microbiota changed significantly for two groups: inulin (F = 2.0239, p = 0.0006 PERMANOVA, Aitchison distance) and isomaltulose (F = 0.67, p = 0.0305). For the tongue microbiota, significant changes were observed for isomaltulose (F = 0.8382, p = 0.0452) and trehalose (F = 1.0119, p = 0.0098). In plaque, 13 species changed significantly for the inulin group, while for tongue coating, three species changed for the trehalose group (ALDEx2, p < 0.1). No significant changes were observed for the secondary outcomes., Conclusion: The effects on the oral microbiota were sweetener dependant with the most pronounced effect on plaque microbiota. Inulin exhibited the strongest microbial modulating potential of the sweeteners tested. Further full-scale clinical studies are required., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Nutrition and oral health are closely related, especially in older adults in whom poor nutrition may lead to oral microbial perturbations, exacerbating poor oral health. In a 6-month randomized controlled trial, we evaluated the effects on oral microbiota and on oral health of dietary advice aimed at increasing protein intake to ≥1.2 g/kg adjusted body weight/day (g/kg aBW/d) in community-dwelling older adults with low habitual protein intake (<1.0 g/kg aBW/d). Food intake was measured via 24 h dietary recalls, oral health was measured via questionnaires, and oral microbial composition was assessed via the 16S rRNA sequencing of tongue swabs. Mean baseline protein intake was 0.8 g/kg aBW/day in both groups. In the high protein group ( n = 47), participants increased their protein intake to mean 1.2 g/kg aBW/day at the 6-month follow-up. Protein intake in the control group ( n = 43) remained at 0.9 g/kg a BW/day. The intervention did not affect self-reported oral health. While it caused moderate shifts in oral microbiota alpha- and beta-diversity measures, abundances of individual bacterial taxa were not affected. In conclusion, our intervention did not affect self-reported oral health within a period of 6 months, nor did it substantially affect the tongue microbiota composition.

Introduction: This crossover randomized controlled trial (RCT) investigated differences in short-term entero-endocrine response to a mixed-meal tolerance test preceded by nutrient sensing between participants with pre-diabetes (pre-T2D) and type 2 diabetes (T2D). Additionally, differences in gut and oral microbiome composition between participants with a high and low entero-endocrine response were investigated., Research Design and Methods: Ten participants with pre-T2D and ten with T2D underwent three test days with pre-loads consisting of either swallowing water (control), or rinsing with a non-nutritive sweetener solution, or swallowing the sweetener solution before a mixed-meal tolerance test. Blood glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, glucose, insulin and peptide YY (PYY) were determined at t = -20, 0, 15, 30, 60, 120 and 240 minutes. The composition of the oral and gut microbiome at baseline were also determined., Results: The entero-endocrine response differed by pre-loads, e.g. a lower PYY response after swallowing the non-nutritive sweetener (-3585.2pg/mL [95% CI: -6440.6; -729.8]; p = 0.01). But it also differed by T2D status, e.g. a higher glucose, glucagon and PYY response was found in participants with T2D, compared to those with pre-T2D. Evidence for associations between the oral and gut microbiome composition and the entero-endocrine response was limited. Still, the level of entero-endocrine response was associated with several oral microbiome measures. Higher oral anterior α-diversity was associated with a lower PYY response (e.g. Inverse Simpson index -1357pg/mL [95% CI -2378; -336; 1.24]), and higher oral posterior α-diversitywith a higher GIP response (e.g. Inverse Simpson index 6773pg/mL [95% CI 132; 13414]) in models adjusted for sex, age and T2D status., Conclusions: Non-nutritive pre-loads influence the entero-endocrine response to a mixed-meal, and this effect varies based on (pre-)T2D status. The entero-endocrine response is likely not associated with the gut microbiome, and there is limited evidence for association with the α-diversity of the oral microbiome composition., Trial Registration: Trial register: Netherlands Trial Register NTR7212, accessible through International Clinical Trials Registry Platform: ICTRP Search Portal (who.int)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Muilwijk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Expert groups argue to raise the recommended daily allowance for protein in older adults from 0.8 to 1.2 g/kg/day to prevent undernutrition. However, protein is thought to increase satiety, possibly through effects on gut microbiota and central appetite regulation. If true, raising daily protein intake may work counterproductively. In a randomized controlled trial, we evaluated the effects of dietary advice aimed at increasing protein intake to 1.2 g/kg adjusted body weight/day (g/kg aBW/day) on appetite and gut microbiota in 90 community-dwelling older adults with habitual protein intake <1.0 g/kg aBW/day (Nintervention = 47, Ncontrol = 43). Food intake was determined by 24-h dietary recalls and gut microbiota by 16S rRNA sequencing. Functional magnetic resonance imaging (fMRI) scans were performed in a subgroup of 48 participants to evaluate central nervous system responses to food-related stimuli. Both groups had mean baseline protein intake of 0.8 ± 0.2 g/kg aBW/day. At 6 months’ follow-up this increased to 1.2 ± 0.2 g/kg aBW/day for the intervention group and 0.9 ± 0.2 g/kg aBW/day for the control group. Microbiota composition was not affected, nor were appetite or brain activity in response to food-related stimuli. Increasing protein intake in older adults to 1.2 g/kg aBW/day does not negatively impact the gut microbiota or suppress appetite.

Background: Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients., Objectives: We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD., Methods: We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life., Results: The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes., Conclusions: Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Older adults are particularly prone to the development of poor appetite and undernutrition. Possibly, this is partly due to the aged gut microbiota. We aimed to evaluate the gut microbiota in relation to both poor appetite and undernutrition in community-dwelling older adults. Furthermore, we studied the causal effects of the microbiota on body weight and body composition by transferring faecal microbiota from cohort participants into germ-free mice., Methods: First, we conducted a cross-sectional cohort study of 358 well-phenotyped Dutch community-dwelling older adults from the Longitudinal Aging Study Amsterdam. Data collection included body measurements, a faecal and blood sample, as well as extensive questionnaires on appetite, dietary intake, and nutritional status. Appetite was assessed by the Council of Nutrition Appetite Questionnaire (CNAQ) and undernutrition was defined by either a low body mass index (BMI) (BMI < 20 kg/m 2 if <70 years or BMI < 22 kg/m 2 if ≥70 years) or >5% body weight loss averaged over the last 2 years. Gut microbiota composition was determined with 16S rRNA sequencing. Next, we transferred faecal microbiota from 12 cohort participants with and without low BMI or recent weight loss into a total of 41 germ-free mice to study the potential causal effects of the gut microbiota on host BMI and body composition., Results: The mean age (range) of our cohort was 73 (65-93); 58.4% was male. Seventy-seven participants were undernourished and 21 participants had poor appetite (CNAQ < 28). A lower abundance of the genus Blautia was associated with undernutrition (log2 fold change = -0.57, Benjamini-Hochberg-adjusted P = 0.008), whereas higher abundances of taxa from Lachnospiraceae, Ruminococcaceae UCG-002, Parabacteroides merdae, and Dorea formicigenerans were associated with poor appetite. Furthermore, participants with poor appetite or undernutrition had reduced levels of faecal acetate (P = 0.006 and 0.026, respectively). Finally, there was a trend for the mice that received faecal microbiota from older adults with low BMI to weigh 1.26 g less after 3 weeks (P = 0.086) and have 6.13% more lean mass (in % body weight, P = 0.067) than the mice that received faecal microbiota from older adults without low BMI or recent weight loss., Conclusions: This study demonstrates several associations of the gut microbiota with both poor appetite and undernutrition in older adults. Moreover, it is the first to explore a causal relation between the aged gut microbiota and body weight and body composition in the host. Possibly, microbiota-manipulating strategies will benefit older adults prone to undernutrition., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

During the SARS-CoV2 pandemic, it has become clear that centralized testing suffers from multiple bottlenecks. Logistics, number of machines, and people available to run the diagnostic tests are limited. A solution to those bottlenecks would be a fully decentralized system, where people can test themselves at home and only report back the outcome of the test in a centralized database. Here a noninstrumental device capable of achieving isothermal conditions useful for detecting the SARS-CoV2 RNA using loop mediated amplification (LAMP) tests is presented. This device, compared to others reported in literature or present on the market, is cheap, easy to produce and use, and has little impact on the environment. Using a simple aluminum coffee capsule, a phase change material, and a 3D printed holder, this device, when placed in boiling water, is able to maintain a temperature of 65 °C for 25 min, required for running the LAMP reaction. In principle, this device can be applied to any LAMP reaction, and hence employed for many different applications, and can be deployed in large quantities in short amount of time., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Global Challenges published by Wiley‐VCH GmbH.)

Poor taste and smell function are widely thought to contribute to the development of poor appetite and undernutrition in older adults. It has been hypothesized that the oral microbiota play a role as well, but evidence is scarce. In a cross-sectional cohort of 356 older adults, we performed taste and smell tests, collected anthropometric measurements and tongue swabs for analysis of microbial composition (16S rRNA sequencing) and Candida albicans abundance (qPCR). Older age, edentation, poor smell and poor appetite were associated with lower alpha diversity and explained a significant amount of beta diversity. Moreover, a lower Streptococcus salivarius abundance was associated with poor smell identification score, whereas high C. albicans abundance seemed to be associated with poor smell discrimination score. In our population, neither the tongue microbiota, nor C. albicans were associated with poor taste or directly with undernutrition. Our findings do suggest a host-microbe interaction with regard to smell perception and appetite., (© 2021. The Author(s).)

Characteristic properties of type III CRISPR-Cas systems include recognition of target RNA and the subsequent induction of a multifaceted immune response. This involves sequence-specific cleavage of the target RNA and production of cyclic oligoadenylate (cOA) molecules. Here we report that an exposed seed region at the 3' end of the crRNA is essential for target RNA binding and cleavage, whereas cOA production requires base pairing at the 5' end of the crRNA. Moreover, we uncover that the variation in the size and composition of type III complexes within a single host results in variable seed regions. This may prevent escape by invading genetic elements, while controlling cOA production tightly to prevent unnecessary damage to the host. Lastly, we use these findings to develop a new diagnostic tool, SCOPE, for the specific detection of SARS-CoV-2 from human nasal swab samples, revealing sensitivities in the atto-molar range., (© 2021. The Author(s).)

Background: Age-related declines in taste and smell function are widely assumed to contribute to the decrease in appetite and the development of undernutrition in older adults., Objectives: Here we aim to assess the associations of both taste and smell function with several nutrition-related outcomes in a single study, with poor appetite and undernutrition as primary outcomes., Methods: This is a cross-sectional cohort study of 359 community-dwelling Dutch older adults, aged 65-93 y. Taste function was measured for all 5 basic tastes. Smell function was assessed with 3 tests: for odor identification, discrimination, and threshold. Self-reported taste and smell, appetite, energy (kcal/d) and macronutrient (% energy) intake, and covariates were assessed with extensive questionnaires. Dietary quality was calculated using the Dutch Healthy Diet index 2015, Alternative Healthy Eating Index 2010, and Mediterranean Diet Score. Body measurements included body weight (current and 2 y prior), height, and body impedance analysis. Data were analyzed via multiple logistic and linear regression., Results: Of our sample, 9.2% had poor taste and 17.0% poor smell, 6.1% had poor appetite, and 21.4% were undernourished. Self-reported poor taste (OR: 8.44; 95% CI: 1.56, 45.56; P = 0.013) was associated with poor appetite, but no other taste or smell score was associated with either poor appetite or undernutrition. Some associations were found of individual taste and smell scores with macronutrient intake and dietary quality. Self-reported poor taste and smell were both consistently associated with poorer dietary quality., Conclusions: In community-dwelling older adults, specific taste and smell impairments may have diverse consequences for appetite, food intake, or dietary quality. However, this does not necessarily result in undernutrition. The consistent associations of self-reported poor taste and smell with poor dietary quality do underline the usefulness of this information when screening for nutritional risk., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: Large longitudinal cohort studies in infants are needed to understand oral microbiome maturation in relation to general health. The logistics of such studies are complex and costs involved high. Methods like home sampling by caretakers might be a solution to these issues. This study aimed to evaluate feasibility of home sampling by caretakers and to assess which oral niche provides the most reliable sample., Methods: In this cross-sectional study 30 mothers and their infants aged 2-15 months participated. Swabs of the tongue, buccal mucosa, saliva, and dental plaque of the mother and the infant were collected by the mother after watching an instruction video. Thereafter, the trained researcher repeated the sample collection. Variations on the sampling protocol were listed. Bacterial DNA was quantified and microbial composition was assessed using 16S rDNA amplicon sequencing., Results: None of the sampled niches appeared to be unfeasible based on interviews and observed variations on protocol. No significant differences in bacterial DNA concentration between operators (mother and researcher) were found. In infant's saliva, Shannon diversity of samples collected by the researcher was significantly higher than those collected by mothers (p = 0.0009) and the bacterial composition was influenced by variations on sampling protocol (p = 0.01)., Conclusions: Home sampling by caretakers is a feasible method for oral sample collection in infants and mothers. Oral samples collected by mothers resemble samples collected by a trained researcher, with the tongue sample being the most similar and saliva the least., Clinical Significance: Home sampling can simplify longitudinal oral microbiota collection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Oral health and dentistry are essential components of systems medicine, which has received lesser attention in comparison to other medical fields, such as cancer biology. In this context, oral polymorphonuclear neutrophils (oPMNs) play an important role in the maintenance of oral health. To the best of our knowledge, this is the first study to report original observations on the transcriptional responses of oPMNs during experimentally induced gingivitis, by temporarily refraining from regular oral care. Oral rinses were prospectively collected at four different time points for oPMNs isolation from healthy volunteers: day 1 (start of the experimental gingivitis challenge), day 9 (during challenge), day 14 (end of the challenge), and day 21 (postchallenge). Transcriptome of oPMNs was determined by RNA sequencing. Differentially expressed genes (DEGs) were selected at p  < 0.01 level, and evaluated for pathway regulation using Ingenuity Pathway Analysis suite. We found four major clusters of DEGs, consisting of 256 initial response DEGs (day 9 only), 221 late response DEGs (day 14 only), 53 persistent responsive DEGs (consistent at day 9 and 14), and 524 DEGs showing responses only in the postchallenge phase (day 21 only). Pathway analysis of the initial and late response DEGs showed involvement in many immune regulatory pathways and PMN function, whereas DEGs at day 21 were associated with epithelial adherence signaling and other miscellaneous related signaling pathways. The results from this pilot study showed that oPMNs mediate oral inflammatory processes, suggesting their immunomodulatory role in oral equilibrium.

Background: To prevent involuntary weight loss in older people, the knowledge about factors affecting body weight (BW) is essential. Therefore, we aimed to investigate the longitudinal associations of multiple oral health aspects with BW in community-dwelling older adults., Methods: This analysis is based on prospective data with a 10-year follow-up of 657 Dutch community-dwelling older adults (age 66.4 ± 5.8 years, 54% female) from the Longitudinal Aging Study Amsterdam. Participants' characteristics, BW, and 12 oral health variables (teeth, dentures, nine oral problems, self-rated oral health) were assessed in 2005/07 and 2015/16. The association between oral health and BW was analyzed by mixed models and adjusted for demographic, socio-economic, smoking, health, and functional aspects considering data of both assessments., Results: Mean BW was 79.1 ± 13.3 kg at baseline (B) and 77.6 ± 13.8 kg at follow-up (FU). At baseline, 29.6% of the participants reported being edentulous (FU:34.4%) and 55.8% to wear dentures (FU:62.3%). Dental pain while chewing was the oral problem with the lowest (B:5.2%, FU:6.6%) and xerostomia with the highest prevalence at both examinations (B:24.3%, FU:30.0%). Most participants rated their oral status as healthy (B:65.2%, FU:66.9%). Neither edentulism and denture use nor oral problems showed a longitudinal association with BW. In contrast, self-rated oral health was associated with BW (b = 0.724, SE = 0.296, p = 0.015) after adjusting for multiple confounders., Conclusions: In community-dwelling older adults self-rated oral health may indicate changes in body weight in the long term. Therefore, this simple measure could serve to identify a risk for weight loss and to initiate oral interventions in clinical practice.

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

Rationale: The respiratory microbiota is increasingly being appreciated as an important mediator in the susceptibility to childhood respiratory tract infections (RTIs). Pathogens are presumed to originate from the nasopharyngeal ecosystem. Objectives: To investigate the association between early life respiratory microbiota and development of childhood RTIs. Methods: In a prospective birth cohort (Microbiome Utrecht Infant Study: MUIS), we characterized the oral microbiota longitudinally from birth until 6 months of age of 112 infants (nine regular samples/subject) and compared them with nasopharyngeal microbiota using 16S-rRNA-based sequencing. We also characterized oral and nasopharynx samples during RTI episodes in the first half year of life. Measurements and Main Results: Oral microbiota were driven mostly by feeding type, followed by age, mode of delivery, and season of sampling. In contrast to our previously published associations between nasopharyngeal microbiota development and susceptibility to RTIs, oral microbiota development was not directly associated with susceptibility to RTI development. However, we did observe an influx of oral taxa, such as Neisseria lactamica , Streptococcus , Prevotella nanceiensis , Fusobacterium , and Janthinobacterium lividum , in the nasopharyngeal microbiota before and during RTIs, which was accompanied by reduced presence and abundance of Corynebacterium , Dolosigranulum , and Moraxella spp. Moreover, this phenomenon was accompanied by reduced niche differentiation indicating loss of ecological topography preceding confirmed RTIs. This loss of ecological topography was further augmented by start of daycare, and linked to consecutive development of symptomatic infections. Conclusions: Together, our results link the loss of topography to subsequent development of RTI episodes. This may lead to new insights for prevention of RTIs and antibiotic use in childhood.

Background: Antibiotic therapy is commonly used in animal agriculture. Antibiotics excreted by the animals can contaminate farming environments, resulting in long term exposure of animals to sub-inhibitory levels of antibiotics. Little is known on the effect of this exposure on antibiotic resistance. In this study, we aimed to investigate the long term effects of sub-inhibitory levels of antibiotics on the gut microbiota composition and resistome of veal calves in vivo. Forty-two veal calves were randomly assigned to three groups. The first group (OTC-high) received therapeutic oral dosages of 1 g oxytetracycline (OTC), twice per day, during 5 days. The second group (OTC-low) received an oral dose of OTC of 100-200 μg per day during 7 weeks, mimicking animal exposure to environmental contamination. The third group (CTR) did not receive OTC, serving as unexposed control. Antibiotic residue levels were determined over time. The temporal effects on the gut microbiota and antibiotic resistance gene abundance was analysed by metagenomic sequencing., Results: In the therapeutic group, OTC levels exceeded MIC values. The low group remained at sub-inhibitory levels. The control group did not reach any significant OTC levels. 16S rRNA gene-based analysis revealed significant changes in the calf gut microbiota. Time-related changes accounted for most of the variation in the sequence data. Therapeutic application of OTC had transient effect, significantly impacting gut microbiota composition between day 0 and day 2. By metagenomic sequence analysis we identified six antibiotic resistance genes representing three gene classes (tetM, floR and mel) that differed in relative abundance between any of the intervention groups and the control. qPCR was used to validate observations made by metagenomic sequencing, revealing a peak of tetM abundance at day 28-35 in the OTC-high group. No increase in resistance genes abundance was seen in the OTC-low group., Conclusions: Under the conditions tested, sub-therapeutic administration of OTC did not result in increased tetM resistance levels as observed in the therapeutic group.

Objectives: The olfactory decline that often accompanies aging is thought to contribute to undernutrition in older adults. It is believed to negatively affect eating pleasure, appetite, food intake and subsequently nutritional status. We have evaluated the associations of olfactory function with BMI, appetite and prospective weight change in a cohort of Dutch community-dwelling older adults., Design: Cross-sectional cohort study., Participants: Dutch community-dwelling older adults from the ongoing Longitudinal Aging Study Amsterdam (LASA). Measurements and setting: In 2012-2013, the 40-item University of Pennsylvania Smell Identification Test (UPSIT) was administered to 824 LASA participants to evaluate their olfactory function. Body weight, height, appetite, comorbidity, cognitive status and socio-demographic factors were also assessed. Follow-up weight was measured after three years., Results: 673 participants (aged 55-65 years) were included in the regression analyses. Median UPSIT-score was 33. When adjusted for potential confounders, lower UPSIT-score (indicative of poorer olfactory function) was not associated with poor appetite (OR = 1.062, p = 0.137) or prospective weight change (B = -0.027, p = 0.548). It was, however, associated with lower BMI in smokers (B = 0.178, p = 0.032), but not in non-smokers (B = -0.015, p = 0.732)., Conclusion: Lower olfactory function scores were associated with lower BMI in community-dwelling older adults who smoke, but not with appetite or prospective weight change. Therefore, smoking older adults with olfactory impairments may pose as a vulnerable group with respect to developing undernutrition., Competing Interests: No competing interests declared

Background: The oral cavity harbors a complex microbial ecosystem, intimately related to oral health and disease. The use of polyol-sweetened gum is believed to benefit oral health through stimulation of salivary flow and impacting oral pathogenic bacteria. Maltitol is often used as sweetener in food products. This study aimed to establish the in vivo effects of frequent consumption of maltitol-sweetened chewing gum on the dental plaque microbiota in healthy volunteers and to establish the cellular and molecular effects by in vitro cultivation and transcriptional analysis. Results: An intervention study was performed in 153 volunteers, randomly assigned to three groups (www.trialregister.nl; NTR4165). One group was requested to use maltitol gum five times daily, one group used gum-base, and the third group did not use chewing gum. At day 0 and day 28, 24 h-accumulated supragingival plaque was collected at the lingual sites of the lower jaw and the buccal sites of the upper jaw and analyzed by 16S ribosomal rRNA gene sequencing. At day 42, 2 weeks after completion of the study, lower-jaw samples were collected and analyzed. The upper buccal plaque microbiota composition had lower bacterial levels and higher relative abundances of (facultative) aerobic species compared to the lower lingual sites. There was no difference in bacterial community structure between any of the three study groups (PERMANOVA). Significant lower abundance of several bacterial phylotypes was found in maltitol gum group compared to the gum-base group, including Actinomyces massiliensis HOT 852 and Lautropia mirabilis HOT 022. Cultivation studies confirmed growth inhibition of A. massiliensis and A. johnsonii by maltitol at levels of 1% and higher. Transcriptome analysis of A. massiliensis revealed that exposure to maltitol resulted in changes in the expression of genes linked to osmoregulation, biofilm formation, and central carbon metabolism. Conclusion: The results showed that chewing itself only marginally impacted the plaque microbiota composition. Use of maltitol-sweetened gum lowered abundance of several bacterial species. Importantly, the species impacted play a key role in the early formation of dental biofilms. Further studies are required to establish if frequent use of maltitol gum impacts early dental-plaque biofilm development.

Rationale: Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time., Objectives: To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life., Methods: In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing., Measurements and Main Results: Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use., Conclusions: Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.

Gingivitis is one of the most common oral infections in humans. While sugar alcohols such as erythritol are suggested to have caries-preventive properties, it may also have beneficial effects in prevention of gingivitis by preventing maturation of oral biofilms. The aim of this study was to assess the effect of erythritol on the microbial ecology and the gingivitis phenotype of oral microcosms. Biofilms were inoculated with stimulated saliva from 20 healthy donors and grown in a gingivitis model in the continuous presence of 0 (control group), 5, and 10% erythritol. After 9 days of growth, biofilm formation, protease activity (gingivitis phenotype), and microbial profile analyses were performed. Biofilm growth was significantly reduced in the presence of erythritol, and this effect was dose dependent. Protease activity and the Shannon diversity index of the microbial profiles of the biofilms were significantly lower when erythritol was present. Microbial profile analysis revealed that presence of erythritol induced a compositional shift from periodontitis- and gingivitis-related taxa toward early colonizers. The results of this study suggest that erythritol suppresses maturation of the biofilms toward unhealthy composition. The gingivitis phenotype was suppressed and biofilm formation was reduced in the presence of erythritol. Therefore, it is concluded that erythritol may contribute to a healthy oral ecosystem in vitro .

Objective: Midlife obesity affects cognition and increases risk of developing dementia. Recent data suggest that intake of the short chain fatty acid butyrate could improve memory function, and may protect against diet-induced obesity by reducing body weight and adiposity., Subjects: We examined the impact of a high-fat diet (HFD) followed by intervention with 5% (w/w) dietary butyrate, on metabolism, microbiota, brain function and structure in the low-density-lipoprotein receptor knockout (LDLr-/-) mouse model in mid and late life., Results: In mid-adult mice, 15 weeks of HFD-induced adiposity, liver fibrosis and neuroinflammation, increased systolic blood pressure and decreased cerebral blood flow, functional connectivity assessed with neuroimaging. The subsequent 2 months butyrate intervention restored these detrimental effects to chow-fed control levels. Both HFD and butyrate intervention decreased variance in fecal microbiota composition. In late-adult mice, HFD showed similar detrimental effects and decreased cerebral white and gray matter integrity, whereas butyrate intervention attenuated only metabolic parameters., Conclusion: HFD induces detrimental effects in mid- and late-adult mice, which can be attenuated by butyrate intervention. These findings are consistent with reported associations between midlife obesity and cognitive impairment and dementia in humans. We suggest that butyrate may have potential in prevention and treatment of midlife obesity.

Introduction: Malnutrition refers to both over- and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance. Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms: 'gastrointestinal microbiota', 'volatile fatty acids', 'malnutrition', 'undernutrition', 'obesity', 'insulin resistance', 'prebiotics', 'probiotics', 'antibiotics' and 'fecal microbiota transplantation'. Expert commentary: Microbiota make important contributions to the regulation of energy balance, whereas microbial disturbances might predispose to malnutrition. If we manage to manipulate the microbiota to our benefit, it could lead to preventive or therapeutic strategies targeting malnutrition.

In the past, epidemiological studies focused on cavitated stages of caries. The arrival of the International Caries Detection and Assessment System (ICDAS) in 2004 allowed for clinical measurements of the initial stages of enamel caries. However, since the introduction, most studies applying the ICDAS still have studied the diseased population. The objective of this cross-sectional observational study was to describe early enamel caries in a large healthy young adult population and determine the relationship with diet and oral hygiene measures. The study population consisted of 268 healthy participants without frank cavitation. The examinations were done visually and radiographically using ICDAS on all tooth surfaces. In total, 8.6% of the surfaces (occlusal > approximal > smooth) had caries, of which 92.0% were confined to enamel (28.5% ICDAS score 1, 54.0% score 2, 8.6% score 3). Thirteen percent of the occlusal and 63% of the approximal caries were found with radiography. Thus, radiography is quintessential for the diagnosis of approximal enamel lesions. We found a positive correlation between enamel caries (ICDAS 1 to 3) and the consumption of mono- and disaccharides and carbohydrates ( r = 0.226 and r = 0.188, respectively, both P < 0.01), as well as a negative correlation with alcohol consumption ( r = -0.202, P < 0.01). There was also a positive correlation between enamel caries and the energy intake from mono- and disaccharides (sugar kJ, r = 0.206, P < 0.01), which was independent of body mass index. Only 11 participants consumed less than 10% of total energy as sugar kJ, which is the recommended percentage of kJ from free sugar by the World Health Organization. No clear correlation was found with oral hygiene. In conclusion, in this healthy young adult population, caries was found in 97.8% of the subjects, mostly initial enamel caries (ICDAS 1 to 2) in the occlusal surface of molars, and was related with dietary factors.

Birth by Caesarian section is associated with short- and long-term respiratory morbidity. We hypothesized that mode of delivery affects the development of the respiratory microbiota, thereby altering its capacity to provide colonization resistance and consecutive pathobiont overgrowth and infections. Therefore, we longitudinally studied the impact of mode of delivery on the nasopharyngeal microbiota development from birth until six months of age in a healthy, unselected birth cohort of 102 children (n=761 samples). Here, we show that the respiratory microbiota develops within one day from a variable mixed bacterial community towards a Streptococcus viridans-predominated profile, regardless of mode of delivery. Within the first week, rapid niche differentiation had occurred; initially with in most infants Staphylococcus aureus predominance, followed by differentiation towards Corynebacterium pseudodiphteriticum/propinquum, Dolosigranulum pigrum, Moraxella catarrhalis/nonliquefaciens, Streptococcus pneumoniae, and/or Haemophilus influenzae dominated communities. Infants born by Caesarian section showed a delay in overall development of respiratory microbiota profiles with specifically reduced colonization with health-associated commensals like Corynebacterium and Dolosigranulum, thereby possibly influencing respiratory health later in life., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)