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The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia , Blautia , Coprococcus , Granulicatella , Holdemania , Oribacterium , Oscillospira , Parabacteroides , and Sutterella . There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia , Blautia , Holdemania , and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles., Competing Interests: The authors declare no conflicts of interest.

To link a clinical outcome with compositional predictors in microbiome analysis, the linear log-contrast model is a popular choice, and the inference procedure for assessing the significance of each covariate is also available. However, with the existence of multiple potentially interrelated outcomes and the information of the taxonomic hierarchy of bacteria, a multivariate analysis method that considers the group structure of compositional covariates and an accompanying group inference method are still lacking. Motivated by a study for identifying the microbes in the gut microbiome of preterm infants that impact their later neurobehavioral outcomes, we formulate a constrained integrative multi-view regression. The neurobehavioral scores form multivariate responses, the log-transformed sub-compositional microbiome data form multi-view feature matrices, and a set of linear constraints on their corresponding sub-coefficient matrices ensures the sub-compositional nature. We assume all the sub-coefficient matrices are possible of low-rank to enable joint selection and inference of sub-compositions/views. We propose a scaled composite nuclear norm penalization approach for model estimation and develop a hypothesis testing procedure through de-biasing to assess the significance of different views. Simulation studies confirm the effectiveness of the proposed procedure. We apply the method to the preterm infant study, and the identified microbes are mostly consistent with existing studies and biological understandings., (© 2021 John Wiley & Sons Ltd.)

Background: The gut microbiome is an important determinant of health and disease in preterm infants., Objectives: The objective of this article was to share our current protocol for other neonatal intensive care units to potentially expand their existing protocols, aiming to characterize the relationship between the intestinal microbiome and health outcomes in preterm infants., Methods: This prospective, longitudinal study planned to recruit 160 preterm infants born <32 weeks gestational age or weighing <1,500 g and admitted to one of two Level III/IV neonatal intensive care units. During the neonatal intensive care unit period, the primary measures included events of early life pain/stress, gut microbiome, host genetic variations, and neurobehavioral assessment. During follow-up visits, gut microbiome; pain sensitivity; and medical, growth, and developmental outcomes at 4, 8-12, and 18-24 months corrected age were measured., Discussion: As of February 14, 2020, 214 preterm infants have been recruited. We hypothesize that infants who experience greater levels of pain/stress will have altered gut microbiome, including potential adverse outcomes such as necrotizing enterocolitis and host genetic variations, feeding intolerance, and/or neurodevelopmental impairments. These will differ from the intestinal microbiome of preterm infants who do not develop these adverse outcomes. To test this hypothesis, we will determine how alterations in the intestinal microbiome affect the risk of developing necrotizing enterocolitis, feeding intolerance, and neurodevelopmental impairments in preterm infants. In addition, we will examine the interaction between the intestinal microbiome and host genetics in the regulation of intestinal health and neurodevelopmental outcomes., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Infant gut microbiota plays a vital role in immune response, mediates neurobehavioral development and health maintenance. Studies of twins' gut microbiota found that gut microbiota composition and diversity tend to be mature and stable with increasing postnatal age (PNA). Preterm infant gut microbiome shifts dramatically when they were staying in the neonatal intensive care unit (NICU). Compositions and shifting characteristics of gut microbiota among neonatal preterm twins and triplets during their early life are still unknown, which impedes a better understanding of the mechanism underpinning neurobehavioral development and precise intervention/health of preterm neonates. This longitudinal cohort study used a twins/triplets design to investigate the interaction of genetic (e.g., male vs. female) and environmental factors influencing the development of the gut microbiome in early life. We included 39 preterm infants, 12 were Female twins/triplets (Female T/T) including 3 twins pairs and 2 triplets, 12 were male twins (Male T) including 6 twins pairs, and 15 were mixed-sex twins/triplets (Mix T/T) including 6 twins pairs and 1 triplet (8 females and 7 males) during the first four weeks of NICU stay. Weekly gut microbiota patterns between females and males were compared by linear discriminant analysis (LDA) effect size (LEfSe). Metagenomics function of gut microbiota was predicted by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Weekly function (KEGG pathways) differences between females and males were detected by using Statistical Analysis of Metagenomic Profiles (STAMP). Results found that female pairs and male pairs were significantly different in gut microbiome diversity, compositions, and predicted metabolic profiles, importantly, females and males were also significantly dissimilar within their co-twin/triplet pairs of the mixed-sex group, infants of co-twins/triplets shared more similar features than un-related infants from different twins' pair. Future research developing personalized interventions for vulnerable high-risk infants should consider sex, and the interaction of sex and environmental factors., 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 Chen, Li, Hird, Chen, Xu, Maas and Cong.)

Objectives: To define gut microbial patterns in preterm infants with and without necrotizing enterocolitis (NEC) and to characterize clinical factors related to the composition of the preterm intestinal microbiome. Methods: Fecal samples were collected at one-week intervals from infants with gestational ages <30 weeks at a single level IV neonatal intensive care unit. Using 16S rRNA gene sequencing, the composition and diversity of microbiota were determined in samples collected from five NEC infants and five matched controls. Hierarchical linear regression was used to identify clinical factors related to microbial diversity and specific bacterial signatures. Results: Low levels of diversity were demonstrated in samples obtained from all preterm infants and antibiotic exposure further decreased diversity among both NEC cases and controls. Fecal microbial composition differed between NEC cases and controls, with a greater abundance of Proteobacteria and bacteria belonging to the class Gammaproteobacteria among NEC infants. Control infants demonstrated a greater abundance of bacteria belonging to the phylum Firmicutes . Conclusion: These findings indicate that an association exists between intestinal Proteobacteria and NEC, and strengthens the notion that an overly exuberant response to Gram-negative products, particularly lipopolysaccharide, in the preterm intestine is involved in NEC pathogenesis. Cumulative exposure to antibiotics corresponded to a reduction in microbial diversity in both NEC cases and controls.

Objective: To examine the effect of feeding type on microbial patterns among preterm infants and to identify feeding factors that promote the colonization of beneficial bacteria., Data Sources: PubMed, Cochrane Database of Systematic Reviews, Scopus, and the Cummulative Index of Nursing and Allied Health Literature were thoroughly searched for articles published between January 2000 and January 2017, using the keywords gut microbiome, gut microbiota, enteral microbiome, enteral microbiota, premature infant, preterm infant, extremely low birth weight infant, ELBW infant, very low birth weight infant, feeding, breast milk, breastfeeding, formula, prebiotic, probiotic, and long chain polyunsaturated fatty acid., Study Selection: Primary studies written in English and focused on the association between enteral feeding and gut microbiome patterns of preterm infants were included in the review., Data Extraction: We independently reviewed the selected articles and extracted information using predefined data extraction criteria including study design, study participants, type of feeding, type and frequency of biospecimen (e.g., feces, gastric aspirate) collection, microbiological analysis method, and major results., Data Synthesis: In 4 of the 18 studies included in the review, researchers described the effects of milk products (mothers' own milk, donor human milk, and formula). In 5 studies, the effects of prebiotics were assessed, and in 9 studies, the effects of probiotics on the gut microbiome were described. Mothers' own breast milk feeding influenced the compositional structure of preterm infants' gut microbial community and increased diversity of gut microbiota compared with donor human milk and formula feeding. The results of the use of prebiotics and probiotics varied among studies; however, the majority of the researchers reported positive bifidogenic effects on the development of beneficial bacteria., Conclusion: Mothers' own milk is considered the best form of nutrition for preterm infants and the gut microbial community. Variation in fatty acid composition across infant feeding types can affect microbial composition. The evidence for supplementation of prebiotics and probiotics to promote the gut microbial community structure is compelling; however, additional research is needed in this area., (Copyright © 2018 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)