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Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth., Competing Interests: Declaration of interests S.V.L. is a board member at, holds stock in, and consults for Siolta Therapeutics. She also consults for the Atria Academy of Science and Medicine and for Sanofi. J.C.C. is co-founder of PrecisionProfile and OncoRx Insights. N.Aghaeepour. is a member of the scientific advisory boards of January AI, Parallel Bio, Celine Therapeutics, and WellSim Biomedical Technologies and is a paid consultant for Mara BioSystems. J.G. and M.S. have filed a patent related to the phylotype generation process., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information., (© 2022. The Author(s).)

Background: In nature, microbial communities undergo changes in composition that threaten their resiliency. Here, we interrogated sourdough, a natural cereal-fermenting metacommunity, as a dynamic ecosystem in which players are subjected to continuous environmental and spatiotemporal stimuli., Results: The inspection of spontaneous sourdough metagenomes and transcriptomes revealed dominant, subdominant and satellite players that are engaged in different functional pathways. The highest microbial richness was associated with the highest number of gene copies per pathway. Based on meta-omics data collected from 8 spontaneous sourdoughs and their identified microbiota, we de novo reconstructed a synthetic microbial community SDG. We also reconstructed SMC-SD43 from scratch using the microbial composition of its spontaneous sourdough equivalent for comparison. The KEGG number of dominant players in the SDG was not affected by depletion of a single player, whereas the subdominant and satellite species fluctuated, revealing unique contributions. Compared to SMC-SD43, SDG exhibited broader transcriptome redundancy. The invariant volatilome profile of SDG after in situ long-term back slopping revealed its stability. In contrast, SMC-SD43 lost many taxon members. Dominant, subdominant and satellite players together ensured gene and transcript redundancy., Conclusions: Our study demonstrates how, by starting from spontaneous sourdoughs and reconstructing these communities synthetically, it was possible to unravel the metabolic contributions of individual players. For resilience and good performance, the sourdough metacommunity must include dominant, subdominant and satellite players, which together ensure gene and transcript redundancy. Overall, our study changes the paradigm and introduces theoretical foundations for directing food fermentations. Video Abstract., (© 2022. The Author(s).)

Background: Early life gut microbiota is involved in several biological processes, particularly metabolism, immunity, and cognitive neurodevelopment. Perturbation in the infant's gut microbiota increases the risk for diseases in early and later life, highlighting the importance of understanding the connections between perinatal factors with early life microbial composition. The present research paper is aimed at exploring the prenatal and postnatal factors influencing the infant gut microbiota composition at six months of age., Methods: Gut microbiota of infants enrolled in the longitudinal, prospective, observational study "A.MA.MI" ( Alimentazione MAmma e bambino nei primi MIlle giorni ) was analyzed. We collected and analyzed 61 fecal samples at baseline (meconium, T0); at six months of age (T2), we collected and analyzed 53 fecal samples. Samples were grouped based on maternal and gestational weight factors, type of delivery, type of feeding, time of weaning, and presence/absence of older siblings. Alpha and beta diversities were evaluated to describe microbiota composition. Multivariate analyses were performed to understand the impact of the aforementioned factors on the infant's microbiota composition at six months of age., Results: Different clustering hypotheses have been tested to evaluate the impact of known metadata factors on the infant microbiota. Neither maternal body mass index nor gestational weight gain was able to determine significant differences in infant microbiota composition six months of age. Concerning the type of feeding, we observed a low alpha diversity in exclusive breastfed infants; conversely, non-exclusively breastfed infants reported an overgrowth of Ruminococcaceae and Flavonifractor . Furthermore, we did not find any statistically significant difference resulting from an early introduction of solid foods (before 4 months of age). Lastly, our sample showed a higher abundance of clostridial patterns in firstborn babies when compared to infants with older siblings in the family., Conclusion: Our findings showed that, at this stage of life, there is not a single factor able to affect in a distinct way the infants' gut microbiota development. Rather, there seems to be a complex multifactorial interaction between maternal and neonatal factors determining a unique microbial niche in the gastrointestinal tract., 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 © 2021 Raspini, Vacca, Porri, De Giuseppe, Calabrese, Chieppa, Liso, Cerbo, Civardi, Garofoli, De Angelis and Cena.)

We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., p-cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD). Twenty-five probiotic strains, belonging to lactobacilli and Bifidobacterium, were tested for their ability to grow in co-culture with different vegetable (pomegranate, tomato, and grapes) sources of antioxidants and prebiotics (inulin, fructo-oligosaccharides, and β-glucans). Probiotics were selected based on the acidification rates and viable cell counts. Inulin and fructo-oligosaccharides reported the best prebiotic activity, while a pomegranate seed extract was initially chosen as antioxidant source. The investigation was also conducted in fecal batches from healthy and CKD subjects, on which metabolomic analyses (profiling volatile organic compounds and total free amino acids) were conducted. Two out of twenty-five probiotics were finally selected. After the stability tests, the selective innovative synbiotic formulation (named NatuREN G) comprised Bifidobacterium animalis BLC1, Lacticaseibacillus casei LC4P1, fructo-oligosaccharides, inulin, quercetin, resveratrol, and proanthocyanidins. Finally, NatuREN G was evaluated on fecal batches collected from CKD in which modified the viable cell densities of some cultivable bacterial patterns, increased the concentration of acetic acid and decane, while reduced the concentration of nonanoic acid, dimethyl trisulfide, and indoxyl sulfate. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is a non-communicable disease resulting from the combination of a genetic predisposition and environmental triggers, possibly including intestinal microbiota composition. However, the relationship between microbiota modulation and other CRC risk factors is still debated. With the intent to shed light on the axis between microbial imbalance and ACF (aberrant crypt foci) development in genetically predisposed individuals, we used the Winnie-APCMin/+ model combining genetics and inflammation. Our results indicate that the mother's microbial composition can be a transmittable risk factor favoring the cascade of events finally resulting in ACF development in the offspring. In light of these results, preventive strategies developed to avoid dysbiosis could help to reduce the risk of tumor lesion onset and progression. These preventive approaches may be particularly effective during pregnancy and lactation to reduce a child's risk of CRC development. Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics. Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother's genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks. Results: ACF development in 8-week-old Winnie-APCMin/+ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development. Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) are debilitating chronic inflammatory disorders that develop as a result of a defective immune response toward intestinal bacteria. Intestinal dysbiosis is associated with the onset of IBD and has been reported to persist even in patients in deep remission. We investigated the possibility of a dietary-induced switch to the gut microbiota composition using Winnie mice as a model of spontaneous ulcerative colitis and chow enriched with 1% Bronze tomato. We used the near isogenic tomato line strategy to investigate the effects of a diet enriched in polyphenols administered to mild but established chronic intestinal inflammation. The Bronze-enriched chow administered for two weeks was not able to produce any macroscopic effect on the IBD symptoms, although, at molecular level there was a significant induction of anti-inflammatory genes and intracellular staining of T cells revealed a mild decrease in IL17A and IFNγ production. Analysis of the microbial composition revealed that two weeks of Bronze enriched diet was sufficient to perturb the microbial composition of Winnie and control mice, suggesting that polyphenol-enriched diets may create unfavorable conditions for distinct bacterial species. In conclusion, dietary regimes enriched in polyphenols may efficiently support IBD remission affecting the intestinal dysbiosis. [ABSTRACT FROM AUTHOR]