Gut Microbial Colonization Research Articles

P1317 Oral microbiota is linked to the propensity for mucosal healing: A prospective oral-gut-stool microbiome analysis in IBD

Abstract Background The oral cavity is the second most complex human microbial niche and is the conduit through which initial gut microbial colonisation occurs during early life. While the gut microbiome is implicated in the pathogenesis of inflammatory bowel disease (IBD), the role of the oral microbiome remains underexplored. We aimed to characterise the oral-gut microbiome in IBD and its association with disease activity and complete mucosal healing (CMH), a key prognostic marker for long-term remission. Methods All patients with Crohn’s disease (CD) and Ulcerative Colitis (UC) were prospectively recruited via www.musicstudy.uk. We conducted a 3-stage experimental approach. (1) We profiled the oral microbiota in IBD vs healthy controls (HC) (CD = 34, UC = 24 and HC = 25). (2) We carried out trans-anatomical oral-ileal-stool microbial source tracking1 within the same patients at a single time-point (CD = 23; inflamed vs. non-inflamed mucosal samples), alongside longitudinal oral-stool sampling (CD = 32, UC = 17). (3) Our machine learning (ML) modelling integrated stool microbiota taxonomic profiles (CD = 53, UC = 11; sampled at 0, 3, and 6 months) with ~80 clinical variables to classify CMH using random forest, AdaBoost, XGBoost, logistic regression, and neural networks. Results 16S rRNA sequencing revealed significant divergence between IBD and HC oral microbiota (PCoA, Bray-Curtis; PERMANOVA, p=0.003). Active disease also differed from remission (PCoA, Bray-Curtis; PERMANOVA, p=0.01). Higher oral Veillonella abundances were associated with IBD; bacteria commonly enriched in the IBD gut. We determined within patient oral microbiota abundances in gut samples and found no difference between inflamed ileal mucosa compared to non-inflamed (p=0.52). Patients who did not achieve CMH exhibited significantly higher oral microbiota abundances in stool compared to those with CMH (β = 0.046, p=0.022, linear mixed-effects model). Oral microbiota abundances in stool correlated with clinical markers of disease activity, calprotectin (r = 0.23, p=0.009) and albumin (r = –0.28, p=0.002; Benjamini-Hochberg adjusted). ML models integrating stool microbiota taxonomic profiles and clinical variables outperformed clinical markers alone in predicting CMH (AUC: 0.79 vs. 0.55), indicating that the inclusion of stool microbiota features could be valuable in predicting CMH in the clinical setting. Conclusion Our data show distinct oral microbiota taxonomic profiles in IBD and active disease, with higher oral microbiota abundances in stool associated with lack of CMH. These findings highlight the oral microbiome as a potential upstream regulator of microbial-immune crosstalk from the site of IBD-inflammation.

Supplementation of Parachlorella sp. in feed promote the gut microbiome colonization and fecal IgA response of broiler in both early and late period

This study evaluated the effects of Parachlorella sp. KSN1 (PA) supplementation on the gut microbiota and intestinal immunity of broilers of different ages. A total of 180 Ross 308 broiler chicks were weighed and divided into early (1 to 10 days post hatch) and late (11 to 28 days post hatch) periods, with six replicates of 10 chicks per cage assigned to two dietary groups. The experimental diets included a corn-soybean meal-based control diet and a treatment diet supplemented with 0.5% PA, replacing corn or corn starch, and fed ad libitum for the assigned experimental period. On days 10 and 28, two broilers from each of the six replicate cages, with 7 broilers per cage in each group, were selected and euthanized, and cecal feces and intestinal tissue samples were collected. PA supplementation did not significantly affect broilers growth performance during both the early and the late periods. However, PA supplementation altered the cecal microbiome, with Clostridiaceae and Clostridium exhibiting prominent and consistent changes. In terms of intestinal immunity, PA supplementation significantly increased the number of CD3+ and CD4+ T cells when administered only during the early period. Cecal IgA levels were significantly increased by PA supplementation during both the early and late periods. A significant positive correlation was observed between IgA, Clostridiaceae and Clostridium during the early and late periods. Gene expression analysis identified 40 upregulated genes, including polymeric immunoglobulin receptor (pIgR), and 142 downregulated genes, including marginal zone B and B1 cell specific protein and immunoglobulin lambda-like polypeptide 1 that were associated with the IgA response in PA-treated broilers during the early period. This study demonstrated that PA supplementation promotes gut microbial colonization and intestinal immunity development during the early age of broilers. These findings suggest that the early growth period of broilers is the optimal time for dietary immunomodulation to promote gut health in broilers.

SOME POTENTIAL PREREQUISITES FOR THE FORMATION OF THE GUT MICROBIOTA IN PREMATURE BABIES: PART III

Abnormal microbial colonization of the gut from birth in newborns aff ects growth, development, and health, leading to short- and long-term adverse eff ects. The microbiota of preterm infants diff ers from that of term infants. This is because preterm infants and their mothers have more complicated prenatal and postnatal health conditions and anatomically- functional immaturity of organs and systems depending on gestational age. Maternal conditions, antibiotics, type of feeding, and use of probiotics can signifi cantly aff ect the gut microbiota of preterm infants in the early neonatal period; however, these eff ects decrease with age. Although some factors and processes are diffi cult to intervene or avoid, understanding the potential factors and determinants will help to develop timely strategies to promote a healthy gut microbiota in preterm infants. This review discusses potential determinants of gut microbial colonization in preterm infants, the underlying mechanisms, and recommendations for addressing adverse eff ects.

Microbiota-dependent in vivo biotransformation, accumulation, and excretion of arsenic from arsenobetaine-rich diet

Arsenobetaine (AB), a major organic arsenic (As) species in seafood, is regarded as safe by current regulatory assessments due to low toxicity and rapid unmodified urinary excretion. This notion has been challenged by reports of AB metabolism by intestinal bacteria in vitro and more recent evidence of in vivo AB metabolism in mice. However, these studies did not establish the causal role of intestinal bacteria in AB transformation in vivo. To address this, we employed gnotobiology and compared the biotransformation of As from naturally AB-rich rodent diet in mice that were either germ-free or colonized with gut microbiota of varying microbial diversity. Our results confirm the in vivo metabolism of AB in the intestine under chronic dietary exposure. The transformation of ingested As was dependent on the presence/absence and complexity of the gut microbiota. Notably, specific toxic As species were absent under germ-free condition. Furthermore, gut microbial colonization was linked to increased As accumulation in the intestinal lumen as well as systemically, along with delayed clearance from the body. These findings emphasize the mammalian gut microbiota as a critical factor in evaluating the safety of AB-accumulating seafoods.

317 Microbial interventions to improve gut health in neonatal ruminants

Abstract Colonization and establishment of a balanced and healthy gut microbiome during the neonatal period can directly and indirectly influence animals by affecting the development and metabolism, nutrition absorption, barrier and immune functions, and endocrine and neuron transmitter secretions. Therefore, neonatal period represents a crucial window of time in animal’s life that induces long-term developmental and immune memory. Therefore, alterations in the early gut microbial composition and colonization trajectories lead to long-term negative effects on animals’ production and health. While the rapidly developing gut microbial community is affected by various external factors due to its instability, it provides a great opportunity for microbial intervention to alter microbial colonization trajectories and their subsequent impact on gut health. Recent advance research has been successful in restoring altered gut microbial communities by using microbial interventions such as vaginal seeding, fecal microbial transplantation, probiotics, and prebiotics. However, there is a lack of understanding on the long-term effects of these interventions on gut health in neonatal ruminants. Direct fed microbes (live naturally existing microbes that can improve health and production performance) with psychobiotic function (a type of probiotic that affect cognitive and behavioral functions of the host via the gut-brain axis) can be one of the novel microbiome solutions to target and alter the microbiome dysbiosis. The use of direct fed microbes, postbiotics and psychobiotics and their potential implications in improving calf health and productivity leads to a novel solution to the manipulation of the gut microbiome in calves.

Gut microbiota in infants with food protein enterocolitis.

We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES). Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis. Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants. We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices.

Effects of ciprofloxacin and levofloxacin on initial colonization of intestinal microbiota in Bufo gargarizans at embryonic stages

Ciprofloxacin (CIP) and levofloxacin (LEV) are broad-spectrum antibiotics with potent antibacterial activity. Although many studies have shown that antibiotics can lead to gut microbiota disruption, the effects of CIP and LEV on gut microbial colonization at the embryonic stage remain poorly characterized. Here, we evaluated the response of Bufo gargarizans embryos in terms of gut microbiota colonization, growth and developmental stages to CIP and LEV exposure. Embryos treated with 100 μg/L CIP and LEV exhibited significantly reduced diversity and richness of the gut microbiota, as well as altered community structure. Both CIP and LEV treatments resulted in an increase in the pathogenic bacteria Bosea and Aeromonas, and they appeared to be more resistant to CIP than LEV. Additionally, CIP exposure caused reduced total length and delayed the development in B. gargarizans embryos, while LEV increased the total length and promoted embryonic development. The present study revealed the adverse effects of CIP and LEV exposure on host gut microbiota, growth and development during the embryonic stage, and contributed new perspectives to the evaluation of early aquatic ecological risk under CIP and LEV exposure.

Early-life factors shaping the gut microbiota of Common buzzard nestlings

BackgroundExploring the dynamics of gut microbiome colonisation during early-life stages is important for understanding the potential impact of microbes on host development and fitness. Evidence from model organisms suggests a crucial early-life phase when shifts in gut microbiota can lead to immune dysregulation and reduced host condition. However, our understanding of gut microbiota colonisation in long-lived vertebrates, especially during early development, remains limited. We therefore used a wild population of common buzzard nestlings (Buteo buteo) to investigate connections between the early-life gut microbiota colonisation, environmental and host factors.ResultsWe targeted both bacterial and eukaryotic microbiota using the 16S and 28S rRNA genes. We sampled the individuals during early developmental stages in a longitudinal design. Our data revealed that age significantly affected microbial diversity and composition. Nest environment was a notable predictor of microbiota composition, with particularly eukaryotic communities differing between habitats occupied by the hosts. Nestling condition and infection with the blood parasite Leucocytozoon predicted microbial community composition.ConclusionOur findings emphasise the importance of studying microbiome dynamics to capture changes occurring during ontogeny. They highlight the role of microbial communities in reflecting host health and the importance of the nest environment for the developing nestling microbiome. Overall, this study contributes to understanding the complex interplay between microbial communities, host factors, and environmental variables, and sheds light on the ecological processes governing gut microbial colonisation during early-life stages.

Early Life Exposures and the Development of the Infant Gut Microbiome: A Review

The influence of the intestinal microbiota on metabolic, nutritional, and immunological processes is widely reported. With increasing literature associating altered microbial compositions with adverse health outcomes, it is important to understand how early life exposures may impact the development of gut microbial colonization and subsequent risk of altered metabolic and immune regulation. The purpose of this review is to describe factors in the maternal prenatal and perinatal period that may impact the intestinal microbiome over the first 2 years of life. A comprehensive search of MEDLINE, EMBASE, and the Cochrane Library using Medical Subject Headings (MeSH) and keywords for studies reporting on determinants of gut microbiota in infants (0 to 24 months) born at full term was conducted. Articles using culture techniques were included but not those that exclusively used molecular techniques that lacked sensitivity. Each citation title and abstract was independently assessed for inclusion for full text review. Findings related to the maternal prenatal period, mode of birthing, infant diet and antibiotics were included. Bifidobacteria and Bacteroides abundance were consistently greater in the first weeks of life in children born vaginally, and increased Bacteroides presence persisted throughout the first year. Bifidobacteria abundance was greater in breastfed children. Introduction of solid food was associated with greater presence of bacteria of the Firmicutes phylum. Although these studies advance our knowledge of how exposures in prenatal, intrapartum, and early life may impact colonization, larger studies with longitudinal follow-up are needed to improve our understanding of how perturbations may contribute to early origins of disease. This article has been peer reviewed.

SOME POTENTIAL REQUIREMENTS FOR THE FORMATION OF THE GUT MICROBIOTA IN PRETERM INFANTS: PART 1

Abnormal microbial colonization of the gut from birth in newborns aff ects growth, development, and health, leading to short- and long-term adverse eff ects. The microbiota of preterm infants diff ers from that of term ones. This is because preterm infants and their mothers have more complicated prenatal and postnatal health conditions and anatomically- functional immaturity of organs and systems depending on gestational age. Maternal conditions, antibiotics, type of feeding, and use of probiotics can signifi cantly aff ect the gut microbiota of preterm infants in the early neonatal period; however, these eff ects decrease with age. Although some factors and processes are diffi cult to intervene or avoid, understanding the potential factors and determinants will help to develop timely strategies to promote a healthy gut microbiota in preterm infants. This review discusses potential determinants of gut microbial colonization in preterm infants,the underlying mechanisms, and recommendations for addressing adverse eff ects.

Human milk microbiome: associations with maternal diet and infant growth.

Ingestion of human milk (HM) is identified as a significant factor associated with early infant gut microbial colonization, which has been associated with infant health and development. Maternal diet has been associated with the HM microbiome (HMM). However, a few studies have explored the associations among maternal diet, HMM, and infant growth during the first 6 months of lactation. For this cross-sectional study, Mam-Mayan mother-infant dyads (n = 64) were recruited from 8 rural communities in the Western Highlands of Guatemala at two stages of lactation: early (6-46 days postpartum, n = 29) or late (109-184 days postpartum, n = 35). Recruited mothers had vaginally delivered singleton births, had no subclinical mastitis or antibiotic treatments, and breastfed their infants. Data collected at both stages of lactation included two 24-h recalls, milk samples, and infant growth status indicators: head-circumference-for-age-z-score (HCAZ), length-for-age-z-score (LAZ), and weight-for-age-z-score (WAZ). Infants were divided into subgroups: normal weight (WAZ ≥ -1SD) and mildly underweight (WAZ < -1SD), non-stunted (LAZ ≥ -1.5SD) and mildly stunted (LAZ < -1.5SD), and normal head-circumference (HCAZ ≥ -1SD) and smaller head-circumference (HCAZ < -1SD). HMM was identified using 16S rRNA gene sequencing; amplicon analysis was performed with the high-resolution ANCHOR pipeline, and DESeq2 identified the differentially abundant (DA) HMM at the species-level between infant growth groups (FDR < 0.05) in both early and late lactation. Using both cluster and univariate analyses, we identified (a) positive correlations between infant growth clusters and maternal dietary clusters, (b) both positive and negative associations among maternal macronutrient and micronutrient intakes with the HMM at the species level and (c) distinct correlations between HMM DA taxa with maternal nutrient intakes and infant z-scores that differed between breast-fed infants experiencing growth faltering and normal growth in early and late lactation. Collectively, these findings provide important evidence of the potential influence of maternal diet on the early-life growth of breastfed infants via modulation of the HMM.

Lactation-related dynamics of bacterial and fungal microbiomes in feces of sows and gut colonization in suckling and newly weaned piglets.

Changes in the gut microbial composition of the sow during lactation may influence the gut microbial colonization in their offspring, for which less information was available in the literature. This study aimed to assess: 1) the changes that occur in the bacterial and fungal communities in sow feces during the 28-d lactation period as well as in gastric and cecal digesta of piglets until one week after weaning, and 2) bacterial and fungal taxa in cecal digesta of the piglets postweaning that associate with fecal consistency. Aside from sow milk, piglets had access to creep feed from day of life (DoL) 3. Fecal samples from sows for microbial analysis were collected (n = 20) on days postpartum (DPP) 1, 6, 13, 20, and 27, as well as from weaned piglets for fecal scoring on DoL 30 and 34. Gastric and cecal digesta of piglets was collected on DoL3, 7, 14, 21, 28, 31, and 35 (n = 5/sex/DoL). Progressing lactation affected bacterial and fungal communities in sow feces, including 10.3- and 3.0-fold increases in the relative abundances of Lactobacillus from DPP1 to 6 and Kazachstania from DPP1 to 13, respectively (P < 0.001). Although time- and gut-site-related differences existed, bacterial and fungal taxa found in sow feces were also present in gastric and cecal digesta of piglets, which supports their role in gut colonization in neonatal piglets. In piglets, bacterial and fungal alpha-diversities showed certain fluctuations during the suckling period, whereby weaning affected the fungal than bacterial diversity at both gut sites (P < 0.05). At both gut sites, Lactobacillus largely increased from DoL3 to 7 and remained a dominating taxon until DoL35 (P < 0.05). Postweaning, plant-glycan fermenters (e.g., Prevotella-9) seemed to replace milk-glycan fermenting Fusobacterium and Bacteroides (P < 0.05). In gastric and cecal digesta, Kazachstania, Tausonia, Candida, and Blumeria were dominating fungi from DoL3 to 35, with Kazachstania becoming even more dominant postweaning (P < 0.001). Fecal consistency was softer on DoL34 than 30 (P < 0.05). Correlation analysis identified that softer feces were linked to the relative abundances of plant-glycan and proteolytic bacterial taxa including pathobionts (e.g., Clostridium sensu stricto) in the cecum on DoL34. However, the potential association between cecal mold and plant-pathogenic fungi Talaromyces, Mrakia, and Blumeria and softer feces are worth investigating in the future in relation to (gut) health of piglets.

Microbial signature of intestine in children with allergic rhinitis.

Previous studies have found that unique patterns of gut microbial colonization in infancy associated with the development of allergic diseases. However, there is no research on the gut microbiota characteristics of AR children in Chinese Mainland. To investigate the changes of gut microbial of AR children in Chinese Mainland and evaluate the correlation between gut microbial and clinical indexes. In this clinical study, fecal samples from 24 AR children and 25 healthy control children (HCs) were comparative via next generation sequencing of the V3-V4 regions of the 16S rRNA gene. Analyzed the relationship between clinical features and gut microbial using Spearman correlation. Compared to HCs, AR children showed significant decreases in Shannon index and significant increases in Simpson index at both the family and genera levels (all p < 0.05). In terms of bacterial composition, at the phylum level, AR children had higher abundance of Bacteroidetes than that in the HCs group (p < 0.05) and were significantly positively correlated with TNSS (p < 0.05). At the family level, AR children had higher abundance of Prevotellaceae and Enterobacteriaceae higher than that in the HCs group (all p < 0.05) and had a significantly positive correlation with TNSS, eosinophils (EOS) and total immunoglobulin E (tIgE) (all p < 0.05). At the genus level, reduced abundance of Agathobacter, Parasutterella, Roseburia and Subdoligranulum were also observed in the AR cohorts compared to HCs (all p < 0.05) and significantly negatively associated with TNSS, EOS, tIgE, QOL, and FeNO (all p < 0.05). AR children in Chinese Mainland were characterized by reduced microbial diversity and distinguished microbial characteristics in comparison with HCs. The observations of this study offer proof that distinctive gut microbiota profiles were present in AR children and necessitate further investigation in the form of mechanistic studies.

Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms.

Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).

Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs.

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3'SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.

Capsulized Fecal Microbiota Transplantation Induces Remission in Patients with Ulcerative Colitis by Gut Microbial Colonization and Metabolite Regulation.

Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.

Metabolic independence drives gut microbial colonization and resilience in health and disease

BackgroundChanges in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.ResultsHere we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.ConclusionsThese observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of “dysbiosis” that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

Abstract 6016: A comprehensive analysis of gut microbiome mediated epigenetic regulation of intestinal stem cells

Abstract Background: Gut microbial colonization, represents a critical time period for establishing the overall health of an individual. The intestine is a highly dynamic tissue with high turnover of intestinal epithelial cells throughout the life span of an individual making intestinal stem cells (ISCs) critical for normal gut homeostasis. Currently, there exists a lack of knowledge in how the gut microbiota regulates DNA methylation to influence the behavior of these ISCs. Aberrant DNA methylation is now documented to be critical in the disease pathogenesis of intestinal disorders such as colorectal cancer, thus understanding how the gut microbiome influences DNA methylation and ISCs is fundamental for improving human health. Methods: We utilized the Lgr5-GFP mouse model in which endogenous GFP expression is driven by the bonafide intestinal stem cell marker Lgr5. These mice were maintained under two different housing conditions, conventional and germ free. We collected mice under the two conditions and performed dissociation of the colon and small intestine epithelial cells using EDTA dissociation. We then analyzed cell populations using flow cytometry, and collected two cell populations: the differentiated cell population (EpiCam +, GFP -) and intestinal stem cell population (EpiCam +, GFP +). To perform a genome wide comprehensive DNA methylation analysis we performed Whole Genome Bisulfite Sequencing (WGBS) which included both stem cell and differentiated cell populations of females and males at the two age groups points (postnatal day 21 (p21) and p100). Results: There was no significant difference in CpG methylation at the global level between the two housing conditions. Next, we analyzed age matched samples from germ free and conventional mice to determine if there are differentially methylated regions (DMRs) associated with the presence of intestinal microbiota. We have identified DMRs that are maintained in germ free stem cells from p21 to p100 compared to conventional mice, as well as DMRs in the differentiated cell population at both ages. Interestingly in our analysis several genes displayed robust hypomethylation of control mice versus germ free mice at the p100 time point in both the stem cell and differentiated cell populations. One such gene, Ifitm3, has been heavily associated with chronic inflammation in the colonic epithelium and a poor risk factor for colonic cancer (Li D et. Al, Clin Cancer Res. 2011). We validated Ifitm3 methylation and expression changes between cohorts using pyrosequencing and RT-PCR respectively. Conclusions: This comprehensive analysis has yielded top candidate genes for studying functional consequences of DNA methylation changes that have been previously linked to severe patient diseases including cancer. Citation Format: Robert Craig Peery, Jiejun Shi, Leah Farmer, Li Yang, Emily Lawrence, Yumei Li, Wei Li, Lanlan Shen. A comprehensive analysis of gut microbiome mediated epigenetic regulation of intestinal stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6016.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Maternal rumen and milk microbiota shape the establishment of early-life rumen microbiota in grazing yak calves

Early-life gut microbial colonization and development exert a profound impact on the health and metabolism of the host throughout the life span. The transmission of microbes from the mother to the offspring affects the succession and establishment of the early-life rumen microbiome in newborns, but the contributions of different maternal sites to the rumen microbial establishment remain unclear. In the present study, samples from different dam sites (namely, oral, rumen fluid, milk, and teat skin) and rumen fluid of yak calves were collected at 6 time points between d 7 and 180 postpartum to determine the contributions of the different maternal sites to the establishment of the bacterial and archaeal communities in the rumen during early life. Our analysis demonstrated that the dam's microbial communities clustered according to the sites, and the calves' rumen microbiota resembled that of the dam consistently regardless of fluctuations at d 7 and 14. The dam's rumen microbiota was the major source of the calves' rumen bacteria (7.9%) and archaea (49.7%) compared with the other sites, whereas the potential sources of the calf rumen microbiota from other sites varied according to the age. The contribution of dam's rumen bacteria increased with age from 0.36% at d 7 to 14.8% at d 180, whereas the contribution of the milk microbiota showed the opposite trend, with its contribution reduced from 2.7% at d 7 to 0.2% at d 180. Maternal oral archaea were the main sources of the calves' rumen archaea at d 14 (50.4%), but maternal rumen archaea became the main source gradually and reached 66.2% at d 180. These findings demonstrated the potential microbial transfer from the dam to the offspring that could influence the rumen microbiota colonization and establishment in yak calves raised under grazing regimens, providing the basis for future microbiota manipulation strategies during their early life.