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Worldwide, fermented foods (FF) are recognized as healthy and safe. Despite the rapid increase of research papers, there is a lack of systematic evaluation of the health benefits and risks of FF. The COST Action CA20128 "Promoting innovation of fermented foods" (PIMENTO) aims to provide a comprehensive assessment on the available evidence by compiling a set of 16 reviews. Seven reviews will cover clinical and biological endpoints associated with major health indicators across several organ systems, including the cardiovascular, gastrointestinal, neurological, immune, and skeletal systems. Nine reviews will address broader biological questions associated with FF including bioactive compounds and vitamin production, nutrient bioavailability and bioaccessibility, the role of FF in healthy diets and personalized nutrition, food safety, regulatory practices, and finally, the health properties of novel and ethnic FF. For each outcome assessed in the reviews, an innovative approach will be adopted based on EFSA's published guidance for health claim submissions. In particular, each review will be composed of three parts: (1) a systematic review of available human studies; (2) a non-systematic review of the mechanism of action related to the clinical endpoints measured by the human studies identified in part 1; and (3) a non-systematic review of the characterization of the FF investigated in the human studies identified in part 1. The evidence and research gaps derived from the reviews will be summarized and published in the form of a strategic road map that will pave the way for future research on FF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Todorovic, Akpinar, Assunção, Bär, Bavaro, Berkel Kasikci, Domínguez-Soberanes, Capozzi, Cotter, Doo, Gündüz Ergün, Guzel, Harsa, Hastaoglu, Humblot, Hyseni, Hosoglu, Issa, Karakaş-Budak, Karakaya, Kesenkas, Keyvan, Künili, Kütt, Laranjo, Louis, Mantzouridou, Matalas, Mayo, Mojsova, Mukherjee, Nikolaou, Ortakci, Paveljšek, Perrone, Pertziger, Santa, Sar, Savary-Auzeloux, Schwab, Starowicz, Stojanović, Syrpas, Tamang, Yerlikaya, Yilmaz, Malagon-Rojas, Salminen, Frias, Chassard and Vergères.)

The early gut microbiota composition is fundamentally important for piglet health, affecting long-term microbiome development and immunity. In this study, the gut microbiota of postparturient dams was compared with that of their offspring in three Finnish pig farms at three growth phases. The differences in fecal microbiota of three study development groups (Good, Poorly, and PrematureDeath) were analyzed at birth (initial exposure phase), weaning (transitional phase), and before slaughter (stable phase). Dam Lactobacillaceae abundance was lower than in piglets at birth. Limosilactobacillus reuteri and Lactobacillus amylovorus were dominantly expressed in dams and their offspring. Altogether 17 piglets (68%) were identified with Lactobacillaceae at the initial exposure phase, divided unevenly among the development groups: 85% of Good, 37.5% of Poorly, and 75% of PrematureDeath pigs. The development group Good was identified with the highest microbial diversity, whereas the development group PrematureDeath had the lowest diversity. After weaning, the abundance and versatility of Lactobacillaceae in piglets diminished, shifting towards the microbiome of the dam. In conclusion, the fecal microbiota of pigs tends to develop towards a similar alpha and beta diversity despite development group and rearing environment., Competing Interests: Vetcare Ltd. (Grant number: 031019; https://www.vetcare.fi/), and A-Farmers Ltd. (Grant number: 281019; https://www.atriatuottajat.fi/) funded the research project of M.H., including this study. Further, at the time this study was conducted, S.B. was an employee of Vetcare Ltd. (Grant number: 031019; https://www.vetcare.fi/). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2024 König 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.)

Background: Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors., Methods: Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed., Results: Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential., Conclusions: A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified., (© 2024. The Author(s).)

Ultra-low-dose computed tomography (ULD-CT) may combine the high sensitivity of conventional computed tomography (CT) in detecting sarcoma pulmonary metastasis, with a radiation dose in the same magnitude as chest X-ray (CXR). Fifty patients with non-metastatic high-grade soft tissue sarcoma treated with curative intention were recruited. Their follow-up involved both CXR and ULD-CT to evaluate their different sensitivity. Suspected findings were confirmed by conventional CT if necessary. Patients with isolated pulmonary metastases were treated with surgery or stereotactic body radiation therapy (SBRT) with curative intent if possible. The median effective dose from a single ULD-CT study was 0.27 mSv (range 0.12 to 0.89 mSv). Nine patients were diagnosed with asymptomatic lung metastases during the follow-up. Only three of them were visible in CXR and all nine in ULD-CT. CXR had therefore only a 33% sensitivity compared to ULD-CT. Four patients were operated, and one had SBRT to all pulmonary lesions. Eight of them, however, died of the disease. Two patients developed symptomatic metastatic recurrence involving extrapulmonary sites+/-the lungs between two imaging rounds. ULD-CT has higher sensitivity for the detection of sarcoma pulmonary metastasis than CXR, with a radiation dose considerably lower than conventional CT.Clinical trial registration: NCT05813808. 04-14-2023., (© 2024. The Author(s).)

Manipulative behaviour that consists of touching or close contact with ears or tails of pen mates is common in pigs and can become damaging. Manipulative behaviour was analysed from video recordings of 45-day-old pigs, and 15 manipulator-control pairs (n = 30) were formed. Controls neither received nor performed manipulative behaviour. Rectal faecal samples of manipulators and controls were compared. 16S PCR was used to identify Lactobacillaceae species and 16S amplicon sequencing to determine faecal microbiota composition. Seven culturable Lactobacillaceae species were identified in control pigs and four in manipulator pigs. Manipulators (p = 0.02) and females (p = 0.005) expressed higher Lactobacillus amylovorus, and a significant interaction was seen (sex * status: p = 0.005) with this sex difference being more marked in controls. Females (p = 0.08) and manipulator pigs (p = 0.07) tended to express higher total Lactobacillaceae. A tendency for an interaction was seen in Limosilactobacillus reuteri (sex * status: p = 0.09). Results suggest a link between observed low diversity in Lactobacillaceae and the development of manipulative behaviour., (© 2024. The Author(s).)

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing., Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity., Evidence Review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where probiotic systematic reviews with meta-analyses might be improved. An expert panel of 21 scientists and physicians with experience on writing and reviewing probiotic reviews and meta-analyses was convened and used a modified Delphi method to develop recommendations for future probiotic reviews., Findings: A total of 206 systematic reviews with meta-analysis components on probiotics were screened and representative examples discussed to determine areas for improvement. The expert panel initially identified 36 items that were inconsistently reported or were considered important to consider in probiotic meta-analyses. Of these, a consensus was reached for 9 recommendations to improve the quality of future probiotic meta-analyses., Conclusions and Relevance: In this study, the expert panel reached a consensus on 9 recommendations that should promote improved reporting of probiotic systematic reviews with meta-analyses and, thereby, assist in clinical decisions regarding the use of probiotics.

Diverse terms have been used in the literature to refer to the health benefits obtained from the administration of non-viable microorganisms or their cell fragments and metabolites. In an effort to provide continuity to this emerging field, the International Scientific Association of Probiotics and Prebiotics (ISAPP) convened a panel of experts to consider this category of substances and adopted the term postbiotic, which they defined as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host." This definition does not stipulate any specific health benefit, finished product, target population or regulatory status. In this perspective article, we focused on postbiotics developed for pharmaceutical uses, including medicinal products and medical devices. We address how this field is regulated for products based on inanimate microorganisms, marketing considerations and existing examples of postbiotics products developed as cosmetics for the skin, for vaginal health, and as orally consumed products. We focus on the European Union for regulatory aspects, but also give examples from other geographical areas., Competing Interests: SL, GV, and SS serves in the board of directors of ISAPP and have been speakers in scientific meetings supported by the industry of postbiotics. CD is inventor of a patent dealing with the use of A. muciniphila and its components in the context of obesity and related disorders. NV was employed by TargEDys and LG was employed by Sandwalk Bioventures., (Copyright © 2023 Vinderola, Druart, Gosálbez, Salminen, Vinot and Lebeer.)

The most common non-melanoma skin cancer is basal cell carcinoma (BCC). Surgery is the gold standard treatment but also non-surgical alternatives are needed. The purpose of this work was to present the early clinical experiences of degraded 4 MeV electron beam as a treatment method for superficial BCC. Twelve patients underwent two weeks radiation therapy treatment with either 5 × 7 Gy or 2 × 12 Gy. There were no significant differences in treatment outcome with different fractionations or lesion locations. The degraded beam method is a safe and valid non-surgical solution for suitable patients with superficial lesions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Assi Valve has received research grant from Helsinki Cancer Center. Other authors have no conflict of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication.]., (© 2023 The Author(s).)

Fermented foods are often erroneously equated with probiotics. Although they might act as delivery vehicles for probiotics, or other 'biotic' substances, including prebiotics, synbiotics, and postbiotics, stringent criteria must be met for a fermented food to be considered a 'biotic'. Those criteria include documented health benefit, sufficient product characterization (for probiotics to the strain level) and testing. Similar to other functional ingredients, the health benefits must go beyond that of the product's nutritional components and food matrix. Therefore, the 'fermented food' and 'probiotic' terms may not be used interchangeably. This concept would apply to the other biotics as well. In this context, the capacity of fermented foods to deliver one, several, or all biotics defined so far will depend on the microbiological and chemical level of characterization, the reproducibility of the technological process used to produce the fermented foods, the evidence for health benefits conferred by the biotics, as well as the type and amount of testing carried out to show the probiotic, prebiotic, synbiotic, and postbiotic capacity of that fermented food., Competing Interests: GV and SS serves in the board of directors of ISAPP and have been speakers in scientific meetings supported by the fermented food industry. PC has been funded by PrecisionBiotics Group, Friesland Campine, Danone, and PepsiCo. He has also received funding to travel to or present at meetings by H&H, the National Dairy Council U.S., PepsiCo and Yakult. MF is the employee of Health and Scientific Affairs, Danone North America and board member of the International Probiotics Association. KS serves in the board of directors of ISAPP. MS serves as the executive science officer/executive director for the International Scientific Association for Probiotics and Prebiotics (ISAPP), has been a paid consultant for Bayer, Pepsico, Smith Gambrell & Russell LLP, Bill and Melinda Gates Foundation, has been a paid speaker for Associated British Foods, European Federation of the Associations of Dietitians, Fairlife, Omnibiotic/Allergosan, Probi, Sanofi, Xpeer, has served on scientific advisory boards for Danone North America, Cargill, Winclove, has served in an unpaid (except for travel reimbursement) for the Advancement of Food and Nutrition Sciences and United States Pharmacopeia. CC is currently employed by the National Dairy Council. HH has received grant funding from Bio-Cat, Danone Research, General Mills, and Tate & Lyle. She has received speaking honorarium from Beneo, DSM, National Dairy Council, PepsiCo, and Tate & Lyle. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vinderola, Cotter, Freitas, Gueimonde, Holscher, Ruas-Madiedo, Salminen, Swanson, Sanders and Cifelli.)

Purpose of Review: The aim is to provide updated information on the concept of postbiotics and recent data on the efficacy of postbiotics for the prevention and treatment of childhood diseases., Recent Findings: In line with a recently proposed consensus definition, a postbiotic is 'a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host'. Although inanimate, postbiotics may exert health benefits. There are only limited data on infant formulas containing postbiotics, but they are well tolerated, support adequate growth and demonstrate no potential identifiable risks, although clinical benefits remain limited. Currently, there is only limited support for postbiotic use for treating diarrhoea and preventing common paediatric infectious diseases in young children. Given the limited evidence, sometimes with a high risk of bias, caution is justified. No data in older children and adolescents are available., Summary: The consensus definition of postbiotics facilitates further research. As not all postbiotics are the same, the type of disease and specific postbiotic studied should be considered when choosing postbiotics for the prevention or treatment of childhood diseases. Additional studies are needed to assess disease conditions responsive to postbiotics. Mechanisms of action of postbiotics need to be evaluated and characterized., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities., Design: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts., Results: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy., Conclusion: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To study (16S rRNA-sequencing) the impact of gestational and corrected ages on the microbiota profile of human milk (HM) of mothers that delivered full-term and pre-term children, HM samples were obtained and classified according to the gestational age as group T (full-term births ≥37 weeks), and group P (pre-term births <37 weeks). Group P was longitudinally followed, and the samples were collected at the full-term corrected gestational age: when the chronological age plus the gestational age were ≥37 weeks (PT group). The HM microbiota composition differed depending on the gestational age (T vs. P). Group T had lower levels of Staphylococcus and higher levels of Rothia and Streptococcus , as compared to group P. The alpha Simpson diversity value was higher in group T than in P, whereas no differences were found between groups T and PT, suggesting a microbial evolution of the composition of group P towards group T over chronological age. Full-term delivery was associated with a greater diversity of microbes in HM. The microbial composition of pre-term HM, at the corrected age, did not show significant differences, as compared to the samples obtained from the full-term group, suggesting that it would be appropriate to consider the corrected age in terms of the composition and the diversity of the milk in future studies.

Faecalibacterium prausnitzii is a promising biomarker of a healthy human microbiota. However, previous studies reported the heterogeneity of this species and found the presence of several distinct groups at the species level among F. prausnitzii strains. Our recent study revealed that methods previously developed for quantification of F. prausnitzii were not specific to the species level because of the heterogeneity within the F. prausnitzii species and the application of 16S rRNA gene, which is an invalid genetic marker for the species. Therefore, previously available data failed to provide information on different groups, which limits our understanding of the importance of this organism for host health. Here, we propose an alternative gene marker for quantification of F. prausnitzii-related taxa. A total of nine group-specific primer pairs were designed by targeting rpoA gene sequences. The newly developed rpoA-based qPCR successfully quantified targeted groups. Application of the developed qPCR assay in six healthy adults revealed marked differences in abundance and prevalence among the different targeted groups in stool samples. The developed assay will facilitate detailed understanding of the impact of Faecalibacterium populations at the group level on human health and to understand the links between depletion of specific groups in Faecalibacterium and different human disorders., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

The term postbiotic was recently defined by an panel of scientists convened by the International Scientific Association of Probiotics and Prebiotics as "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. " This definition focused on the progenitor microbial cell or cell fragments, not just metabolites, proteins or carbohydrates they might produce. Although such microbe-produced constituents may be functional ingredients of the preparation, they are not required to be present in a postbiotic according to this definition. In this context, terms previously used such as paraprobiotics, ghostbiotics, heat-inactivated probiotics, non-viable probiotics, cell fragments or cell lysates, among others, align with the term postbiotics as conceived by this definition. The applications of postbiotics to infant nutrition and pediatric and adult gastroenterology, mainly, are under development. Some applications for skin health are also underway. As postbiotics are composed of inanimate microorganisms, they cannot colonize the host. However, they can in theory modify the composition or functions of the host microbiota, although evidence for this is scarce. Clinical results are promising, but, overall, there is limited evidence for postbiotics in healthy populations. For example, postbiotics have been studied in fermented infant formulas. The regulation of the term postbiotic is still in its infancy, as no government or international agency around the world has yet incorporated this term in their regulation., Competing Interests: The authors declared to be part of the board of directors of the International Scientific Association of Probiotics and Prebiotics (ISAPP). MS has been compensated for consulting, giving presentations or serving on advisory boards for: Associated British Foods, Bayer, Bill and Melinda Gates Foundation, Bloom, California Dairy Research Foundation, Cargill, Church and Dwight, Danone North America, Danone Research, Fairlife, GlaxoSmithKline, Kerry, Mead Johnson, Omnibiotic/Allergosan, Pepsico, Probi, Sanofi, Trouw Nutrition, Winclove Probiotics, and Yakult. HS has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for: Arla, Else, BioGaia, Biocodex, Danone, Dicofarm, Hipp, Nestlé/Nestlé; Nutrition Institute, and Mead Johnson. GV, HS, and SS gave lectures in scientific events supported by companies that produce infant formula with postbiotics., (Copyright © 2022 Vinderola, Sanders, Salminen and Szajewska.)

The nuclear export factor CRM1-mediated pathway is known to be important for the nuclear egress of progeny parvovirus capsids in the host cells with virus-mediated cell cycle arrest at G2/M. However, it is still unclear whether this is the only pathway by which capsids exit the nucleus. Our studies show that the nuclear egress of DNA-containing full canine parvovirus. capsids was reduced but not fully inhibited when CRM1-mediated nuclear export was prevented by leptomycin B. This suggests that canine parvovirus capsids might use additional routes for nuclear escape. This hypothesis was further supported by our findings that nuclear envelope (NE) permeability was increased at the late stages of infection. Inhibitors of cell cycle regulatory protein cyclin-dependent kinase 1 (Cdk1) and pro-apoptotic caspase 3 prevented the NE leakage. The change in NE permeability could be explained by the regulation of the G2/M checkpoint which is accompanied by early mitotic and apoptotic events. The model of G2/M checkpoint activation was supported by infection-induced nuclear accumulation of cyclin B1 and Cdk1. Both NE permeability and nuclear egress of capsids were reduced by the inhibition of Cdk1. Additional proof of checkpoint function regulation and promotion of apoptotic events was the nucleocytoplasmic redistribution of nuclear transport factors, importins, and Ran, in late infection. Consistent with our findings, post-translational histone acetylation that promotes the regulation of several genes related to cell cycle transition and arrest was detected. In conclusion, the model we propose implies that parvoviral capsid egress partially depends on infection-induced G2/M checkpoint regulation involving early mitotic and apoptotic events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mattola, Mäntylä, Aho, Salminen, Leclerc, Oittinen, Salokas, Järvensivu, Hakanen, Ihalainen, Viiri and Vihinen-Ranta.)

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract with worldwide increasing incidence. Recent studies indicate that certain species of intestinal bacteria are strongly associated with IBD. Helper T lymphocytes are not only the key players in mediating host defense against a wide variety of pathogens but also contribute to pathogenesis of many immune-related diseases. Here, using the T cell transfer model of colitis, we observed that the mice maintained in a specific-pathogen free (SPF) unit after receiving naïve CD4 +  T cells developed mild disease. The same mice developed different degrees of disease when they were maintained in a conventional animal facility (non-SPF), where some pathogens were detected during routine health monitoring. Consistently, increased circulating inflammatory cytokines as well as Th1 and Th17 cells were detected in mice housed in non-SPF units. 16S rRNA sequencing of feces samples enabled us to identify changes in the microbiota composition of mice kept in different facilities. Our data indicate that environmental factors influence gut microbiota composition of mice, leading to development of colitis in a T-cell-dependent manner. In conclusion, changes in environmental conditions and microbial status of experimental animals appear to contribute to progression of colitis.

Background: Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization., Methods: Fecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3-4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing., Results: Preterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode., Conclusions: The initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth., Impact: The initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode. Our study provides new evidence regarding the early gut colonization patterns in preterm infants. Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention., (© 2021. The Author(s).)

The scientific community has proposed terms such as non-viable probiotics, paraprobiotics, ghostbiotics, heat-inactivated probiotics or, most commonly, postbiotics, to refer to inanimate microorganisms and/or their components that confer health benefits. This article addresses the various characteristics of different definitions of 'postbiotics' that have emerged over past years. In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined a postbiotic as "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". This definition of postbiotic requires that the whole or components of inactivated microbes be present, with or without metabolic end products. The definition proposed by ISAPP is comprehensive enough to allow the development of postbiotics from different microorganisms, to be applied in different body sites, encouraging innovation in a promising area for any regulatory category and for companion or production animals, and plant or human health. From a technological perspective, probiotic products may contain inanimate microorganisms, which have the potential to impart a health benefit. However, their contribution to health in most cases has not been established, even if at least one probiotic has been shown to confer the same health benefit by live or inanimate cells.

Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While NS1 is linked to important nuclear processes required for viral replication, much less is known about the role of NS2. Specifically, the function of canine parvovirus (CPV) NS2 has remained undefined. Here we have used proximity-dependent biotin identification (BioID) to screen for nuclear proteins that associate with CPV NS2. Many of these associations were seen both in noninfected and infected cells, however, the major type of interacting proteins shifted from nuclear envelope proteins to chromatin-associated proteins in infected cells. BioID interactions revealed a potential role for NS2 in DNA remodeling and damage response. Studies of mutant viral genomes with truncated forms of the NS2 protein suggested a change in host chromatin accessibility. Moreover, further studies with NS2 mutants indicated that NS2 performs functions that affect the quantity and distribution of proteins linked to DNA damage response. Notably, mutation in the splice donor site of the NS2 led to a preferred formation of small viral replication center foci instead of the large coalescent centers seen in wild-type infection. Collectively, our results provide insights into potential roles of CPV NS2 in controlling chromatin remodeling and DNA damage response during parvoviral replication., Competing Interests: The authors have declared that no competing interests exist.

Food allergy (FA) affects the quality of life of millions of people worldwide and presents a significant psychological and financial burden for both national and international public health. In the past few decades, the prevalence of allergic disease has been on the rise worldwide. Identified risk factors for FA include family history, mode of delivery, variations in infant feeding practices, prior diagnosis of other atopic diseases such as eczema, and social economic status. Identifying reliable biomarkers that predict the risk of developing FA in early life would be valuable in both preventing morbidity and mortality and by making current interventions available at the earliest opportunity. There is also the potential to identify new therapeutic targets. This narrative review provides details on the genetic, epigenetic, dietary, and microbiome influences upon the development of FA and synthesizes the currently available data indicating potential biomarkers. Whereas there is a large body of research evidence available within each field of potential risk factors, there is a very limited number of studies that span multiple methodological fields, for example, including immunology, microbiome, genetic/epigenetic factors, and dietary assessment. We recommend that further collaborative research with detailed cohort phenotyping is required to identify biomarkers, and whether these vary between at-risk populations and the wider population. The low incidence of oral food challenge-confirmed FA in the general population, and the complexities of designing nutritional intervention studies will provide challenges for researchers to address in generating high-quality, reliable, and reproducible research findings., (Copyright © 2021 © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Domesticated horses live under different conditions compared with their extinct wild ancestors. While housed, medicated and kept on a restricted source of feed, the microbiota of domesticated horses is hypothesized to be altered. We assessed the fecal microbiome of 57 domestic and feral horses from different locations on three continents, observing geographical differences. A higher abundance of eukaryota (p < 0.05) and viruses (p < 0.05) and lower of archaea (p < 0.05) were found in feral animals when compared with domestic ones. The abundance of genes coding for microbe-produced enzymes involved in the metabolism of carbohydrates was significantly higher (p < 0.05) in feral animals regardless of the geographic origin. Differences in the fecal resistomes between both groups of animals were also noted. The domestic/captive horse microbiomes were enriched in genes conferring resistance to tetracycline, likely reflecting the use of this antibiotic in the management of these animals. Our data showed an impoverishment of the fecal microbiome in domestic horses with diet, antibiotic exposure and hygiene being likely drivers. The results offer a view of the intestinal microbiome of horses and the impact of domestication or captivity, which may uncover novel targets for modulating the microbiome of horses to enhance animal health and well-being., (© 2022. The Author(s).)

Faecalibacterium prausnitzii has been suggested as a biomarker of a healthy microbiota in human adults. Here, we report a taxonomic study of F. prausnitzii using genomic information and evaluation of the quantitative real-time PCR (qPCR) assay by focusing on specific primers to quantify its population. Average nucleotide identity values revealed that strains deposited as F. prausnitzii in a public database were separated into eight genomogroups with significant differences at the species level. A total of six of the 10 primer pairs used in the previous studies for qPCR of F. prausnitzii contained sequence mismatches to 16S rRNA gene sequences of the tested strains with markedly different levels by in silico analysis. In vitro primer evaluation by qPCR generally agreed with the in silico analysis, and markedly reduced amount of DNA was recorded by qPCR in combination with the primer pairs containing sequence mismatches. The present study demonstrated that a part of the accumulated knowledge on F. prausnitzii is maybe based on biased results., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Objective: The aim of the study was to investigate the impact of intrapartum antibiotic treatment (IAT) on the compositional development of gut microbiota in healthy term infants., Study Design: A case-control study of 24 infants exposed to and 24 matched infants not exposed to IAT was conducted. All subjects were born by vaginal delivery at term and breastfed. None of the infants received antibiotics during the immediate neonatal period. Fecal samples were obtained at the ages of 1 and 6 months. The composition of the intestinal microbiota was assessed by 16S rRNA gene sequencing., Results: IAT was associated with reduced microbial richness but not diversity at 1 month of age. Furthermore, the relative abundances of Clostridiaceae and Erysipelotrichaceae were significantly altered in infants exposed to IAT as compared to nonexposed infants at 1 month of age. The observed deviations in gut microbiota composition between infants exposed and not exposed to IAT diminished by the age of 6 months., Conclusions: IAT is associated with short-term perturbations in the gut microbiota development in healthy term, vaginally delivered, breastfed infants. The composition of the gut microbiota is mostly restored by the age of 6 months., (© 2021 S. Karger AG, Basel.)

Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion provides conclusions not only on capsid transport but also on the properties of the nuclear environment during infection. We utilized live-cell imaging and single-particle tracking to characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin was marginalized toward the nuclear envelope it presented a restrictive barrier to the capsids. However, later in infection this barrier became more permissive and the probability of capsids to enter the chromatin increased. Thus, although chromatin marginalization initially restricted capsid transport to the nuclear envelope, a structural reorganization of the chromatin counteracted that to promote capsid transport later. Analyses of capsid motion revealed that it was subdiffusive, and that the diffusion coefficients were lower in the chromatin than in regions lacking chromatin. In addition, the diffusion coefficient in both regions increased during infection. Throughout the infection, the capsids were never enriched at the nuclear envelope, which suggests that instead of nuclear export the transport through the chromatin is the rate-limiting step for the nuclear egress of capsids. This provides motivation for further studies by validating the importance of intranuclear transport to the life cycle of HSV-1., Competing Interests: The authors have declared that no competing interests exist.

Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

With a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping genes to maximise the usage of its genome. An example is the recently found ORF in the cap gene, encoding membrane-associated accessory protein (MAAP), located in the same genomic region as the VP1/2 unique domain, but in a different reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confirm that MAAP translation initiates from the first CTG codon found in the VP1 ORF2. We have further observed MAAP localised in the plasma membrane, in the membranous structures in close proximity to the nucleus and to the nuclear envelope by co-transfecting with plasmids encoding the wild-type AAV (wt-AAV) genome and adenovirus (Ad) helper genes. While keeping VP1/2 protein sequence identical, both inactivation and truncation of MAAP translation affected the emergence and intracellular distribution of the AAV capsid proteins. We have demonstrated that MAAP facilitates AAV replication and has a role in controlling Ad infection. Additionally, we were able to improve virus production and capsid integrity through a C-terminal truncation of MAAP while other modifications led to increased packaging of contaminating, non-viral DNA. Our results show that MAAP plays a significant role in AAV infection, with profound implications for the production of therapeutic AAV vectors., (© 2021. The Author(s).)

Acute respiratory infections are a common cause of morbidity in infants and young children. This high rate of respiratory infections in early life has a major impact on healthcare resources and antibiotic use, with the associated risk of increasing antibiotic resistance, changes in intestinal microbiota composition and activity and, consequently, on the future health of children. An international group of clinicians and researchers working in infant nutrition and cow's milk allergy (CMA) met to review the available evidence on the prevalence of infections in healthy infants and in those with allergies, particularly CMA; the factors that influence susceptibility to infection in early life; links between infant feeding, CMA and infection risk; and potential strategies to modulate the gut microbiota and infection outcomes. The increased susceptibility of infants with CMA to infections, and the reported potential benefits with prebiotics, probiotics and synbiotics with regard to improving infection outcomes and reducing antibiotic usage in infants with CMA, makes this a clinically important issue that merits further research.

In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term 'postbiotics' is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products., (© 2021. The Author(s).)

The interest on plant-based fermented food is in raise in Western countries. The aim of this study was to select interleukin (IL)-10 inducing strains for the development of potential probiotic plant-based fermented foods. Departing from a collection of 52 lactic acid bacteria (LAB) strains derived from plant material, in vitro co-culture with murine macrophages allowed us to narrow down the number of candidates to 21 strains able to induce IL-10 secretion. 14 of these strains were able to promote the production of tumour necrosis factor-α too. The capacity to induce IL-6 was used to further reduce the number of strains to 4, from which Lactiplantibacillus plantarum subsp. plantarum LpAv was selected to ferment oat and carrots. L. plantarum LpAv was able to ferment oat and carrots until reaching counts of ca. 10 8 and 10 9 cfu/ml. Fermented oat and carrots were orally administered to mice for 10 consecutive days and challenged with a single infective dose of Salmonella enterica serovar. Typhimurium. Counts of L. plantarum LpAv in fermented carrots were 9.23±0.05 cfu/ml and 9.27±0.01 cfu/ml, at day 1 and 10 of the feeding period. Fermented carrots were able to confer enhanced protection (80% of survival) against infection, when compared to control mice (less than 25% of survival). However, L. plantarum LpAv administered as pure culture was not able to confer protection against Salmonella infection. L. plantarum LpAv was selected among 52 plant-derived LAB and it was able to ferment oat and carrots, being only fermented carrots able to confer enhanced protection against Salmonella infection. A succession of in vitro to in vivo tests is proposed as a tool to narrow down the number of candidates when searching for potential novel probiotics from a collection of autochthonous strains.

Parvoviruses are small single-stranded (ss) DNA viruses, which replicate in the nucleoplasm and affect both the structure and function of the nucleus. The nuclear stage of the parvovirus life cycle starts at the nuclear entry of incoming capsids and culminates in the successful passage of progeny capsids out of the nucleus. In this review, we will present past, current, and future microscopy and biochemical techniques and demonstrate their potential in revealing the dynamics and molecular interactions in the intranuclear processes of parvovirus infection. In particular, a number of advanced techniques will be presented for the detection of infection-induced changes, such as DNA modification and damage, as well as protein-chromatin interactions.

Adhesion to intestinal mucus is the first step for microbiota colonization in early life. Polyamines are polycations with important physiological functions in both procaryotic and eucaryotic cells. However, their role in intestinal mucus adhesion is not known. The objective of the present study was to evaluate whether exogenous polyamines (putrescine, spermidine, spermine, and their combination) would alter the adhesive properties of Lacticaseibacillus rhamnosus GG (LGG), Bifidobacterium animalis subs. lactis Bb12, Cronobacter sakazakii , and Escherichia coli . Human intestinal mucus was isolated from healthy infants (0-6-month-old and 6-12-month-old) and healthy adults (25-52 years old). Spermidine significantly increased Bb12 adhesion ( p < 0.05) in the mucus of infants (0-6 months) but reduced the adhesion of LGG in adult mucus ( p < 0.05) with no significant effect in any of the infant groups. Spermine was more effective than polyamine combinations in reducing C. sakazakii ( p < 0.05) adhesion in early infant mucus (0-6 months). The adhesion ability of E. coli remained unaffected by exogenous polyamines at any age in the concentrations tested. Our data suggest that polyamines may modulate the bacterial adhesion to mucus depending on the bacterial strain and depending at what age the mucus has been generated.

[Table: see text] Following the adoption of Regulation (EU) 2015/2283 on novel foods, the European Commission requested EFSA develop scientific and technical guidance for the preparation and submission of applications for authorisation of novel foods. This guidance presents a common format for the organisation of the information to be presented by the applicant when preparing a well-structured application to demonstrate the safety of the novel food. It outlines the data needed for the safety assessments of novel foods. Requirements relate to the description of the novel food, production process, compositional data, specification, proposed uses and use levels, and anticipated intake of the novel food. Further sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, nutritional information, toxicological information and allergenicity should be considered by the applicant by default. If not covered in the application, this should be justified. The applicant should integrate the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they should be discussed in relation to the anticipated intakes of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use. This guidance was originally adopted in 2016.It has beenrevised to informapplicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.This revised guidance applies to all dossiers submitted as of 27 March 2021. The 2016 version of this guidance remains applicable to applications submitted before 27 March 2021., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

The development of the infant gut microbiota is initiated during pregnancy and continued through early life and childhood, guided by the immediate environment of the child. Our aim was to characterize the shared microbiota between dogs and children as well as to determine whether introduction to dogs of a dog-specific probiotic combination modifies the transfer process. We studied 31 children from allergic families with pet dog(s) and 18 control families without a dog. Altogether 37 dogs were randomized for a 4-week period in a double-blind design to receive canine-derived probiotic product containing a mixture of L. fermentum , L. plantarum , and L. rhamnosus , or placebo. Fecal samples from children and dogs were taken before and after the treatment. Distinctive gut microbiota composition was observed in children with dogs compared to those without a dog, characterized by higher abundance of Bacteroides and short-chain fatty acid producing bacteria such as Ruminococcus and Lachnospiraceae. Probiotic intervention in dogs had an impact on the composition of the gut microbiota in both dogs and children, characterized by a reduction in Bacteroides . We provide evidence for a direct effect of home environment and household pets on children microbiota and document that modification of dog microbiota by specific probiotics is reflected in children's microbiota.

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

We studied the fecal lactobacilli count and species diversity of growing pigs along with immune parameters associated with intestinal lactobacilli. Thirty pigs categorized as small (S, n = 12) or large (L, n = 18) at birth were followed from birth to slaughter in two commercial herds, H1 and H2. Herds differed in terms of their general management. We determined sow colostrum quality, colostrum intake, piglet serum immunoglobulins, and pig growth. We took individual fecal samples from pigs in the weaning and finishing units. We studied lactobacilli count and identified their diversity with 16S PCR. Total lactobacilli count increased in H1 and decreased in H2 between samplings. Lactobacilli species diversity was higher in H1 in both fecal sampling points, whereas diversity decreased over time in both herds. We identified altogether seven lactobacilli species with a maximum of five (one to five) species in one herd. However, a relatively large proportion of lactobacilli remained unidentified with the used sequencing technique. Small pigs had higher lactobacilli counts in both herds but the difference was significant only in H2 ( p = 0.01). Colostrum quality was numerically better in H1 than in H2, where colostrum intake tended to be associated with total lactobacilli count ( p = 0.05).

We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery., Competing Interests: The authors declare there are no competing interests., (©2020 Koffert et al.)

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria's saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health.

Breast milk can be a source of potential probiotic bacteria, but the technological capacity of isolates obtained from this source is not always guaranteed. We aimed at isolating lactobacilli from breast milk samples collected in Argentina, focusing on isolates with functional and technological potential as probiotics. Fourteen Lactobacillus and one Bifidobacterium isolates were obtained from 164 samples donated by 104 mothers. The isolates preliminarily identified by MALDI-TOF, and then the identity was confirmed by partial 16S rRNA gene sequencing. Hydrophobicity was determined (hexadecane and xylene partition). The strains were also co-cultured with murine RAW 264.7 macrophages for screening the capacity to induce the anti-inflammatory cytokine interleukin (IL)-10. Hydrophobicity ranged from 7.4 and 95.9%. The strains Lactobacillus gasseri (70a and 70c) and Lactobacillus plantarum (73a and 73b) were the strains with a higher capacity to induce IL-10 production by macrophages. The technological application was evaluated by freezing dried in 10% lactose or 10% polydextrose. The survival was assessed after accelerated (37 °C, 4 weeks) or long-term (5 and 25 °C, 12 months) storage. Except for Lactobacillus gallinarum 94d, strains lost less than 1 Log10 order cfu/g after long-term (12 months) storage at 5 °C in lactose and polydextrose as protectants. A low correlation between survival to accelerated and long-term storage tests was observed. L. gasseri (70a and 70c) and L. plantarum (73a and 73b) deserve further studies as potential probiotics due to their capacity to induce IL-10 from murine macrophages and their hydrophobicity. In special, L. plantarum 73a was able to confer enhanced protection against Salmonella infection by promoting the immunity of the small intestine.

Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainly Bacteroides and Bifidobacterium , which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of the Prevotella type, with decreasing levels of Bifidobacterium , thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning. The fecal Bifidobacterium in children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor.

Controversial glyphosate-based herbicides (GBHs) are the most frequently used herbicides globally. GBH residues in the wild, in animal and human food may expose non-target organisms to health risks, yet the developmental and cumulative effects of GBHs on physiology and reproduction remain poorly understood. We present the first long-term study on the effects of subtoxic GBH exposure (160 mg/kg) on multiple key physiological biomarkers (cellular oxidative status and neurotransmitters), gut microbiome, reproductive hormones, and reproduction in an avian model. We experimentally exposed in Japanese quail females and males (Coturnix japonica) to GBHs and respective controls from the age of 10 days-52 weeks. GBH exposure decreased hepatic activity of an intracellular antioxidant enzyme (catalase), independent of sex, but did not influence other intracellular oxidative stress biomarkers or neurotransmitter enzyme (acetylcholinesterase). GBH exposure altered overall gut microbiome composition, especially at a younger age and in females, and suppressed potentially beneficial microbes at an early age. Many of the microbial groups increased in frequency from 12 to 28 weeks under GBH exposure. GBH exposure decreased male testosterone levels both at sexual maturity and at 52 weeks of exposure, but did not clearly influence reproduction in either sex (maturation, testis size or egg production). Future studies are needed to characterize the effects on reproductive physiology in more detail. Our results suggest that cumulative GBH exposure may influence health and reproduction-related traits, which is important in predicting their effects on wild populations and global poultry industry., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Sustainable Development goals for 2020 included reducing all causes associated with infant and perinatal mortality in their priorities. The use of compounds with bioactive properties has been proposed as a therapeutic strategy due to their stimulating effect on the host's immune system. Additionally, biotherapeutic products such as postbiotics, tentatively defined as compounds produced during a fermentation process that support health and well-being, promote intestinal barrier integrity without posing considerable risks to children's health. Although this is a concept in development, there are increasing studies in the field of nutrition, chemistry, and health that aim to understand how postbiotics can help prevent different types of infections in priority populations such as minors under the age of five. The present review aims to describe the main mechanisms of action of postbiotics. In addition, it presents the available current evidence regarding the effects of postbiotics against pathogens commonly involved in pediatric infections. Postbiotics may constitute a safe alternative capable of modulating the cellular response and stimulating the host's humoral response.

Objective: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated., Materials and Methods: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05)., Results: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens., Conclusion: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP., Clinical Relevance: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548., Competing Interests: E.I DuPont de Nemours & Co. Danisco Sweeteners Oy provided financial support in the form of a salary for ACO and donated probiotics. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Apilactobacillus kunkeei FF30-6 isolated from healthy honey bees synthesizes the bacteriocin, which exhibits antimicrobial activity against Melissococcus plutonius . The bacteriocin, kunkecin A, was purified through three-step chromatography, and mass spectrometry revealed that its relative molecular mass was 4218.3. Edman degradation of purified kunkecin A showed only the N-terminal residue, isoleucine. Hence, alkaline alkylation made the subsequent amino acid residues accessible to Edman degradation, and 30 cycles were sequenced with 11 unidentified residues. Whole genome sequencing of A. kunkeei FF30-6, followed by Sanger sequencing, revealed that the genes encoding the proteins involved in lantibiotic biosynthesis were within the plasmid, pKUNFF30-6. Most of the identified proteins exhibited significant sequence similarities to the biosynthetic proteins of nisin A and its variants, such as subtilin. However, the kunkecin A gene cluster lacked the genes corresponding to nisI , nisR , and nisK of the nisin A biosynthetic gene cluster. A comparison of the gene products of kukA and nisA (kunkecin A and nisin A structural genes, respectively) suggested that they had similar post-translational modifications. Furthermore, the structure of kunkecin A was proposed based on a comparison of the observed and calculated relative molecular masses of kunkecin A. The structural analysis revealed that kunkecin A and nisin A had a similar mono-sulfide linkage pattern. Purified kunkecin A exhibited a narrow antibacterial spectrum, but high antibacterial activity against M. plutonius . Kunkecin A is the first bacteriocin to be characterized in fructophilic lactic acid bacteria and is the first nisin-type lantibiotic found in the family Lactobacillaceae ., (Copyright © 2020 Zendo, Ohashi, Maeno, Piao, Salminen, Sonomoto and Endo.)