Gut Colonization Research Articles

Effect of vaccine diluents on the colonisation of Salmonella Typhimurium vaccine in chickens

One of the commonly used methods to control on-farm Salmonella outbreaks in the poultry industry is vaccination. Vaccine diluents may affect vaccine efficacy but there are limited studies on how different diluents affect the colonization of live, attenuated vaccines. In this study, buffered peptone water, Marek's diluent and water were used as the diluents to reconstitute the commercially available Salmonella Typhimurium vaccine (Vaxsafe® ST). The diluent reconstituted vaccine was then given to day-old layer hens to test its effects on gut colonization. The vaccine reconstituted in Marek's diluent and buffered peptone water had a significantly higher colonization rate at 7 days post- vaccination in liver, spleen, oesophagus, crop, and proventriculus. At 14 days post-vaccination, there was a significantly higher vaccine load in the upper digestive tract of chickens that received vaccine reconstituted in Marek's diluent and buffered peptone water. The Marek's diluent and buffered peptone water reconstituted vaccine had a higher detection rate in the chicken's liver and spleen. Colonisation with water as a diluent was higher than the others especially in the lower parts of the intestine at 7 days post-vaccination. There was non-significant variation in the antibody titers at 7- and 14-days post-vaccination. In general, the results demonstrated that the use of nutrient-rich diluents in reconstituting live, attenuated Salmonella vaccine can enhance vaccine colonization. This study establishes a foundation for future work aimed at optimising strategies for vaccine reconstitution, crucial for eliciting a robust immune response in the host.

A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen Candida glabrata.

Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C. glabrata MDR isolates, particularly in the host, is poorly characterized, and studies of FLZR isolate fitness have produced contradictory findings. Two important host niches for C. glabrata are macrophages, in which it survives and proliferates, and the gut. Herein we used a collection of clinical and lab-derived C. glabrata isolates to show that FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates and that this fitness cost is reversed by acquiring ECR mutations. Interestingly, dual-RNAseq revealed that macrophages infected with drug-resistant isolates mount an inflammatory response whereas intracellular drug-resistant cells downregulate processes required for in-host adaptation. Furthermore, drug-resistant isolates were outcompeted by their susceptible counterparts during gut colonization and in infected kidneys, while showing comparable fitness in the spleen. Collectively, our study shows that macrophage-rich organs, such as the spleen, favor the retention of MDR isolates of C. glabrata.

Randomized Clinical Trials Demonstrate the Safety Assessment of Alkalihalobacillus clausii AO1125 for Use as a Probiotic in Humans

(1) Background: Alkalihalobacillus clausii AO1125 is a Gram-positive, motile, spore-forming bacterium with potential as a probiotic due to its broad-spectrum antimicrobial activity, inhibiting pathogens like Listeria monocytogenes, Staphylococcus aureus, and Clostridium difficile, as well as anti-rotavirus activity. Its resilience in gastrointestinal conditions suggests benefits for gut health. This study evaluates the safety and probiotic potential of A. clausii AO1125. (2) Methods: Genome annotation identified genes linked to probiotic traits such as stress resistance, gut colonization, immune modulation, and antimicrobial production. The genome was screened for antibiotic resistance genes using CARD, bacteriocin clusters using BAGEL4, and virulence factors via VFDB. Cytotoxicity was assessed on Vero cells and erythrocytes, and a Phase I, double-blind, placebo-controlled clinical trial was conducted with 99 healthy volunteers (50 AO1125, 49 placebo). (3) Results: Genomic analysis confirmed minimal antibiotic resistance genes and the absence of virulence factors, supporting safety. A. clausii AO1125 showed no pathogenicity, cytotoxicity, or hemolytic activity and was well-tolerated in clinical settings, with mild, transient abdominal gas as the most common adverse event. (4) Conclusions: The safety profile and genetic basis for probiotic and antimicrobial properties support A. clausii AO1125 as a promising probiotic candidate for gastrointestinal health, warranting further clinical research.

Mobile genetic elements: the hidden puppet masters underlying infant gut microbiome assembly?

The gut microbiota is important for healthy infant development. Part of the initial colonizing microbial strains originate from the maternal gut, and undergo a selective event, termed the “colonization bottleneck”. While vertical mother-to-infant inheritance and subsequent colonization of bacteria have previously been studied, the role of mobile genetic elements (MGEs) in the infant gut microbiota assembly is unclear. In this perspective article, we discuss how horizontally and vertically transmitted phages and conjugative elements potentially have important roles in infant gut microbiota assembly and colonization through parasitic and mutualistic interactions with their bacterial hosts. While some of these MGEs are likely to be detrimental to their host survival, in other contexts, they may help bacteria colonize new niches, antagonize other bacteria, or protect themselves from other parasitic MGEs in the infant gut. As a result, the horizontal transfer of MGEs likely occurs at high rates in the infant gut, contributing to gene transfer between bacteria and affecting which bacteria can pass the colonization bottleneck. We conclude by highlighting the potential in silico , in vitro , and in vivo methodological approaches that could be employed to study the transmission and colonization dynamics of MGEs and bacteria in the infant gut.

Molecular insights into the evolutionary trajectory of a Klebsiella aerogenes clinical isolate with a complex trade-off between resistance and virulence.

The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three Klebsiella aerogenes isolates recovered from blood samples or deep abscess cultures from the same patient: the wild-type strain (CT_WT), a piperacillin-tazobactam-resistant strain (CT_PENI), and an extended-spectrum-cephalosporin (ESC)-resistant strain (CT_R). Whole-genome sequencing revealed that CT_PENI had acquired a TEM-1 β-lactamase with a mutated promoter, accounting for overproduction. CT_PENI then acquired an E240G substitution in the TEM-1 β-lactamase (resulting in TEM-207) and lost the porin-encoding ompK36 gene to give CT_R. All three strains showed the same virulence in a mouse model of intraperitoneal infection. The results of recombination and transformation assays indicated that when present separately, the TEM-207 overproduction and the ompK36 gene deletion had only small effects on susceptibility to ESCs. However, the combination of the two changes led to a much lower susceptibility to ESCs. Moreover, the levels of fitness in vitro and in vivo in a murine model of gut colonization were significantly lower after TEM-1 β-lactamase overproduction and lower still after E240G substitution and OmpK36 loss. We hypothesize that the chosen courses of antibiotics led to the stepwise emergence of a clone with resistance to penicillins and ESCs and no loss of virulence. However, acquired resistance may have a fitness cost that limits evolutionary success. Our results might explain why the overproduction of extended-spectrum β-lactamases (which should confer a high level of piperacillin-tazobactam resistance) is not observed in clinical practice and why TEM-207 has rarely been detected in clinical isolates.

Bacterial small RNA makes a big impact for gut colonization

The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host & Microbe issue, El Mouali etal. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S.copri by regulating bacterial degradation of complex dietary carbohydrates.

Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.

While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural "super-donor" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.

Bacteriophages targeting Enterococcus faecalis enhance the therapeutic efficacy of levodopa in an MPTP-induced Parkinson’s disease mouse model with E. faecalis gut colonization

Despite the intensive research on gut microbiome-associated diseases over the past 20 years, pharmacological methods for effectively eliminating pathobionts remain unsatisfactory. This study investigated the therapeutic potential of bacteriophages against Enterococcus faecalis, in which bacterial tyrosine decarboxylase (TDC) converts orally administered levodopa (L-DOPA) to dopamine, in an MPTP mouse model of Parkinson’s disease (PD). E. faecalis bacteriophages PBEF62, PBEF66, and PBEF67 (4 × 1010 PFU total/200 µl/day), and E. faecalis cells (2 × 109 CFU/200 µl/day) were orally administered at 2-h intervals before every MPTP (i.p.) and/or L-DOPA (p.o.) treatments for 13 days. The relative abundances of E. faecalis cells and bacteriophages in the feces peaked at 4 and 12 h after administration and gradually decreased by 12 and 48 h, respectively. While the administration of E. faecalis cells eliminated the beneficial effect of L-DOPA on MPTP-induced behavioral deficits, as assessed by cylinder and rotarod tests, the co-administration of bacteriophages with bacterial cells restored this effect. The modulating effects of L-DOPA, E. faecalis, and bacteriophages on PD behavior were closely associated with choline acetyltransferase expression levels in the striatum but not with tyrosine hydroxylase in the substantia nigra of each group. Recurrence and extinction of PD behaviors following treatment with E. faecalis and/or bacteriophages were also coincident with the dopamine levels in the blood and brain tissues of PD mice. The effectiveness of L-DOPA was restored after the three types of E. faecalis bacteriophages selectively eliminated E. faecalis cells, along with the TDC gene copies and transcripts responsible for converting L-DOPA to dopamine in the gastrointestinal tract. In conclusion, a combination of bacteriophages PBEF62, PBEF66, and PBEF67 targeting E. faecalis demonstrates potential as a valuable supplement to L-DOPA therapy for PD.

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-day 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 for gut colonization in neonatal piglets. In piglets, bacterial and fungal alpha-diversities showed certain fluctuations during the suckling period, whereby weaning affected more 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 to investigate in the future in relation to (gut) health of piglets.

Metal availability shapes early life microbial ecology and community succession.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

Type VI secretion systems promote intraspecific competition and host interactions in a bee gut symbiont

The Type VI Secretion System (T6SS) is a sophisticated mechanism utilized by gram-negative bacteria to deliver toxic effector proteins into target cells, influencing microbial community dynamics and host interactions. In this study, we investigated the role of T6SSs in Snodgrassella alvi wkB2, a core bacterial symbiont of the honey bee gut microbiota. We generated single- and double-knockout mutants targeting essential genes (tssD and tssE) in both T6SS-1 and T6SS-2 and assessed their colonization and competition capabilities in vivo. Our results indicate that T6SSs are nonessential for colonization of the bee gut, although T6SS-2 mutant strains exhibited significantly lower colonization levels compared to the wild-type (WT) strain. Further, a defined community experiment showed that S. alvi wkB2 T6SSs do not significantly impact interspecific competition among core gut bacteria. However, cocolonization experiments with closely related S. alvi strains demonstrated that T6SS-1 plays a role in mediating intraspecific competition. Transcriptomic analysis of bee guts monocolonized by WT or T6SS mutants revealed differential expression of host immunity-related genes relative to microbiota-deprived bees, such as upregulation of the antimicrobial peptide apidaecin in the presence of WT S. alvi and the antimicrobial peptide defensin in the presence of T6SS-2 mutant S. alvi, suggesting that T6SSs contribute to shaping host immune responses. These findings provide insight into the ecological roles of T6SSs in the honey bee gut microbiota, emphasizing their importance in maintaining competitive dynamics and influencing host-bacterial interactions.

Amino acid competition shapes Acinetobacter baumannii gut carriage.

Antimicrobial resistance is an urgent threat to human health. Asymptomatic colonization is often critical for persistence of antimicrobial-resistant pathogens. Gut colonization by the antimicrobial-resistant priority pathogen Acinetobacter baumannii is associated with increased risk of clinical infection. Ecological factors shaping A. baumannii gut colonization remain unclear. Here we show that A. baumannii and other pathogenic Acinetobacter evolved to utilize the amino acid ornithine, a non-preferred carbon source. A. baumannii utilizes ornithine to compete with the resident microbiota and persist in the gut in mice. Supplemental dietary ornithine promotes long-term fecal shedding of A. baumannii. By contrast, supplementation of a preferred carbon source-monosodium glutamate (MSG)-abolishes the requirement for A. baumannii ornithine catabolism. Additionally, we report evidence for diet promoting A. baumannii gut carriage in humans. Together, these results highlight that evolution of ornithine catabolism allows A. baumannii to compete with the microbiota in the gut, a reservoir for pathogen spread.

Layer segmented filamentous bacteria colonize and impact gut health of broiler chickens.

In commercial poultry farms, chicks hatch away from their progenitors from which they acquire key host-specific microbiota, like segmented filamentous bacteria (SFB) involved in gut maturation in early life. This study investigated whether providing chicken SFB to newly hatched broilers would increase their gut maturation and resistance to bacteria relevant to broiler and human health. One-day-old Ross308 broilers were orally treated with either phosphate-buffered saline (CON) or layer-derived SFB (D-SFB). On days 5, 10, 17, and 24, feces were collected to detect and enumerate SFB and Enterobacteriaceae. On days 8, 15, 22, and 29, birds were euthanized, intestinal samples were collected to detect and enumerate SFB through quantitative PCR (qPCR) and microscopy and expression of genes associated with gut immune function through reverse transcription-qPCR. This study showed that, despite their host specificity, layer SFB can colonize their genetically distinct relative broilers. Ileal SFB colonization was accelerated by a week with the SFB treatment and covered the proximal, medial, and distal sections of the ileum. Colonization of the ileum by SFB in early life highly activated gene expression of intestinal barrier proteins and cytokines, e.g., IL-10 and IFNγ but not IL-17. SFB treatment reduced the level of Enterobacteriaceae in the gut and provided superior resistance to intestinal and extraintestinal pathogens as tested in vitro. Overall, early gut colonization of SFB is imperative for the maturation of the gut immune system and the establishment of a homeostatic gut environment. Improving our understanding of gut immune maturation in food-producing animals is crucial for both human and animal health.IMPORTANCEIn commercial farms, newly hatched chicks may lack host-specific microbiota that help mature their gut immune system for lifelong health benefits. Here, introducing an avian segmented filamentous bacteria (SFB) to commercially sourced chickens orally at hatch accelerated SFB colonization of the ileum. Remarkably, SFB from layers were able to colonize broilers and enhance gut immune maturation, and this immunomodulation impacted the ability to increase intestinal and extraintestinal resistance to bacteria relevant to poultry and human health. With the antibiotic restrictions in animal production, strategies that will help mitigate infections are urgently needed. In summary, we developed a live prophylactic for newly hatched chicks to improve animal health and food safety. Due to the host specificity of SFB, our data highlight the importance of investigating the molecular mechanism of SFB interaction in their own host.

Impact of Bifidobacterium longum Subspecies infantis on Pediatric Gut Health and Nutrition: Current Evidence and Future Directions.

Background: the intestinal microbiota, a complex community vital to human health, is shaped by microbial competition and host-driven selective pressures. Among these microbes, Bifidobacterium plays a crucial role in early gut colonization during neonatal stages, where Bifidobacterium longum subspecies infantis (B. infantis) predominates and is particularly prevalent in healthy breastfed infants. Objectives: as we embark on a new era in nutrition of the pediatric population, this study seeks to examine the existing understanding regarding B. infantis, encompassing both preclinical insights and clinical evidence. Methods: through a narrative disceptation of the current literature, we focus on its genetic capacity to break down various substances that support its survival and dominance in the intestine. Results: using "omics" technologies, researchers have identified beneficial mechanisms of B. infantis, including the production of short-chain fatty acids, serine protease inhibitors, and polysaccharides. While B. infantis declines with age and in various diseases, it remains a widely used probiotic with documented benefits for infant and child health in numerous studies. Conclusions: the current scientific evidence underscores the importance for ongoing research and clinical trials for a deeper understanding of B. infantis's role in promoting long-term health.

Outer membrane barrier impairment by envC deletion reduces gut colonization of Crohn's disease pathobiont Escherichia coli.

Adherent-invasive Escherichia coli (AIEC) has been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract. The presence of Enterobacteriaceae, including AIEC, is heightened in the intestines of CD patients. Therefore, inhibiting AIEC colonization in the gastrointestinal tract could be a promising therapeutic intervention for CD. This study aims to assess the potential of EnvC as a novel therapeutic target, examining how disrupting EnvC activity through the deletion of the envC gene decreases AIEC gut colonization levels. EnvC serves as a catalyst for peptidoglycan (also called murein) amidases, facilitating bacterial cell division. An AIEC mutant lacking the envC gene exhibited impaired cell division. Furthermore, envC deletion led to a diminished outer membrane barrier, as seen in our finding that the envC mutant became susceptible to vancomycin. Finally, we found that the envC mutant is impaired in competitive gut colonization in a dysbiotic mouse model. The colonization defects might be attributable to reduced resistance to colonic bile acids, as evidenced by our finding that increased colonic levels of bile acids inhibited the colonization of the gastrointestinal tract by AIEC strains. The present findings suggest that targeting bacterial cell division through the inhibition of EnvC activity could represent a promising intervention for CD.

Virulence-linked adhesin drives mutualist colonization of the bee gut via biofilm formation.

Bacterial biofilms are stable multicellular structures that can enable long term host association. Yet, the role of biofilms in supporting gut mutualism is still not fully understood. Here, we investigate Snodgrassella alvi, a beneficial bacterial symbiont of honey bees, and find that biofilm formation is required for its colonization of the bee gut. We constructed fifteen S. alvi mutants containing knockouts of genes known to promote colonization with putative roles in biofilm formation. Genes required for colonization included staA and staB, encoding trimeric autotransporter adhesins (TAAs) and mltA, encoding a lytic transglycosylase. Intriguingly, TAAs are considered virulence factors in pathogens but support mutualism by the symbiont S. alvi. In vitro, biofilm formation was reduced in ΔstaB cells and abolished in the other two mutants. Loss of staA also reduced auto-aggregation and cell-cell connections. Based on structural predictions, StaA/B are massive (>300 nm) TAAs with many repeats in their stalk regions. Further, we find that StaA/B are conserved across Snodgrassella species, suggesting that StaA/B-dependent colonization is characteristic of this symbiont lineage. Finally, staA deletion increases sensitivity to bactericidal antimicrobials, suggesting that the biofilm indirectly buffers against antibiotic stress. In all, the inability of two biofilm-deficient strains (ΔstaA and ΔmltA) to effectively mono-colonize bees indicates that S. alvi biofilm formation is required for colonization of the bee gut. We envision the bee gut system as a genetically tractable model for studying the physical basis of biofilm-mutualist-gut interactions.

From dysbiosis to disease: Tracing gut microbiota's role in neonatal sepsis

IntroductionNeonatal sepsis remains a critical health issue, contributing significantly to morbidity and mortality among preterm infants. Dysbiosis, an imbalance in gut microbiota, is increasingly recognized as a key factor influencing the susceptibility to sepsis. This study aims to elucidate these associations by tracing gut microbiota development in preterm neonates. Methodology: A prospective cohort study was conducted at a tertiary care hospital in Karnataka, India, involving 182 preterm neonates (gestational age <37 weeks, birth weight <1500 g) from January 2021 to September 2023. Two cohorts were defined: Cohort 1 (Healthy neonates) and Cohort 2 (Neonates with sepsis). Stool samples were collected on day 4 and day 14 for microbiological analysis. Conventional culture techniques were used to identify bacterial isolates. ResultsThe study included 182 neonates, equally divided between two cohorts. On Day 4, Cohort 1 had 45 % E. coli and 44 % Klebsiella pneumoniae, which decreased to 40.7 % and 40.7 % by Day 14, respectively. Conversely, Bifidobacterium spp. increased from 30.8 % to 52.7 %. Cohort 2 exhibited higher persistence of pathogenic bacteria, with Klebsiella pneumoniae increasing from 70.3 % to 74.7 % and E. coli from 38.5 % to 51.6 %. Mode of delivery significantly influenced gut flora, with NVD linked to higher beneficial bacteria prevalence (Enterococcus faecalis and Bifidobacterium spp.). ConclusionThe study highlights significant differences in gut microbial patterns between healthy and sepsis neonates, emphasizing the role of initial gut colonization in neonatal health outcomes. Factors such as delivery mode and prenatal antibiotic exposure significantly impact gut microbiota composition, influencing infection susceptibility.

The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization

The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with health and disease states. However, the intrinsic factors that determine its ability to colonize the gut effectively remain largely unknown. By extensive transcriptome mapping of S.copri and examining human-derived samples, we discover a small RNA, which we name Segatella RNA colonization factor (SrcF), and show that SrcF is essential for S.copri gut colonization in gnotobiotic mice. SrcF regulates genes involved in nutrient acquisition, and complex carbohydrates, particularly fructans, control its expression. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by the breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates mediates interspecies signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a critical regulator in gut colonization.

Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice.

Malnutrition is linked to 45% of global childhood mortality, however, the impact of maternal malnutrition on the child's health remains elusive. Previous studies suggested that maternal malnutrition does not affect breast milk composition. Yet, malnourished children often develop a so-called environmental enteropathy, assumed to be triggered by frequent pathogen uptake and unfavorable gut colonization. Here, we show in a murine model that maternal malnutrition induces a persistent inflammatory gut dysfunction in the offspring that establishes during nursing and does not recover after weaning onto standard diet. Early intestinal influx of neutrophils, impaired postnatal development of gut-regulatory functions, and expansion of Enterobacteriaceae were hallmarks of this enteropathy. This gut phenotype resembled those developing under deficient S100a8/a9-supply via breast milk, which is a known key factor for the postnatal development of gut homeostasis. We could confirm that S100a8/a9 is lacking in the breast milk of malnourished mothers and the offspring's intestine. Nutritional supply of S100a8 to neonates of malnourished mothers abrogated the aberrant development of gut mucosal immunity and microbiota colonization and protected them lifelong against severe enteric infections and non-infectious bowel diseases. S100a8 supplementation after birth might be a promising measure to counteract deleterious imprinting of gut immunity by maternal malnutrition.

Host-Pathogen Interactions during Shiga Toxin-Producing Escherichia coli Adherence and Colonization in the Bovine Gut: A Comprehensive Review.

Shiga toxin-producing Escherichia coli (STEC) is a significant public health threat due to its ability to cause severe gastrointestinal diseases in humans, ranging from diarrhea to life-threatening conditions such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). As the primary reservoir of STEC, cattle play a crucial role in its transmission through contaminated food and water, posing a considerable risk to human health. This comprehensive review explores host-pathogen interactions during STEC colonization of the bovine gut, focusing on the role of gut microbiota in modulating these interactions and influencing disease outcomes. We integrated findings from published transcriptomics, proteomics, and genomics studies to provide a thorough understanding of how STEC adheres to and colonizes the bovine gastrointestinal tract. The insights from this review offer potential avenues for the development of novel preventative and therapeutic strategies aimed at controlling STEC colonization in cattle, thereby reducing the risk of zoonotic transmission.