Dynamics Of Gut Microbiota Research Articles

Circadian Rhythm Perturbation Aggravates Gut Microbiota Dysbiosis in Dextran Sulfate Sodium-Induced Colitis in Mice.

Circadian rhythm disruption is increasingly considered an environmental risk factor for the development and exacerbation of inflammatory bowel disease. We have reported in a previous study that nychthemeral dysregulation is associated with an increase in intestinal barrier permeability and inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. To investigate the effect of circadian rhythm disruption on the composition and diversity of the gut microbiota (GM), sixty male C57BL/6J mice were initially divided to two groups, with the shifted group (n = 30) exposed to circadian shifts for three months and the non-shifted group (n = 30) kept under a normal light-dark cycle. The mice of the shifted group were cyclically housed for five days under the normal 12:12 h light-dark cycle, followed by another five days under a reversed light-dark cycle. At the end of the three months, a colitis was induced by 2% DSS given in the drinking water of 30 mice. Animals were then divided into four groups (n = 15 per group): sham group non-shifted (Sham-NS), sham group shifted (Sham-S), DSS non-shifted (DSS-NS) and DSS shifted (DSS-S). Fecal samples were collected from rectal content to investigate changes in GM composition via DNA extraction, followed by high-throughput sequencing of the bacterial 16S rRNA gene. The mouse GM was dominated by three phyla: Firmicutes, Bacteroidetes and Actinobacteria. The Firmicutes/Bacteroidetes ratio decreased in mice with induced colitis. The richness and diversity of the GM were reduced in the colitis group, especially in the group with inverted circadian rhythm. Moreover, the GM composition was modified in the inverted circadian rhythm group, with an increase in Alloprevotella, Turicibacter, Bacteroides and Streptococcus genera. Circadian rhythm inversion exacerbates GM dysbiosis to a less rich and diversified extent in a DSS-induced colitis model. These findings show possible interplay between circadian rhythm disruption, GM dynamics and colitis pathogenesis.

Synergistic bioconversion of organic waste by black soldier fly (Hermetia illucens) larvae and thermophilic cellulose-degrading bacteria.

This study examines the optimum conversion of Wuzhishan pig manure by Black Soldier Fly Larvae (BSFL) at various phases of development, as well as the impact of gut microbiota on conversion efficiency. In terms of conversion efficiency, BSFL outperformed the growing pig stage (GP) group, with significantly higher survival rates (96.75%), fresh weight (0.23 g), and larval conversion rate (19.96%) compared to the other groups. Notably, the GP group showed significant dry matter reductions (43.27%) and improved feed conversion rates (2.17). Nutritional composition varied, with the GP group having a lower organic carbon content. High throughput 16S rRNA sequencing revealed unique profiles, with the GP group exhibiting an excess of Lactobacillus and Clostridium. Promising cellulose-degrading bacteria in pig manure and BSFL intestines, including Bacillus cereus and Bacillus subtilis, showed superior cellulose degradation capabilities. The synergy of these thermophilic bacteria with BSFL greatly increased conversion efficiency. The BSFL1-10 group demonstrated high growth and conversion efficiency under specific conditions, with remarkable larval moisture content (71.11%), residual moisture content (63.20%), and waste reduction rate (42.28%). This study sheds light on the optimal stages for BSFL conversion of pig manure, gut microbiota dynamics, promising thermophilic cellulose-degrading bacteria, and the significant enhancement of efficiency through synergistic interactions. These findings hold great potential for sustainable waste management and efficient biomass conversion, contributing to environmental preservation and resource recovery.

Gut microbiome in two high-altitude bird populations showed heterogeneity in sex and life stage.

Gut microbiotas have important impacts on host health, reproductive success, and survival. While extensive research in mammals has identified the exogenous (e.g. environment) and endogenous (e.g. phylogeny, sex, and age) factors that shape the gut microbiota composition and functionality, yet avian systems remain comparatively less understood. Shorebirds, characterized by a well-resolved phylogeny and diverse life-history traits, present an ideal model for dissecting the factors modulating gut microbiota dynamics. Here, we provide an insight into the composition of gut microbiota in two high-altitude (ca. 3200m above sea level) breeding populations of Kentish plover (Charadrius alexandrinus) and Tibetan sand plover (Charadrius altrifrons) in the Qinghai-Tibetan Plateau, China. By analysing faecal bacterial communities using 16S rRNA sequencing technology, we find a convergence in gut microbial communities between the two species, dominated by Firmicutes, Proteobacteria, and Bacteroidetes. This suggests that the shared breeding environment potentially acts as a significant determinant shaping their gut microbiota. We also show sex- and age-specific patterns of gut microbiota: female adults maintain a higher diversity than males, and juveniles are enriched in Rhizobiaceae and Exiguobacterium due to their vegetative food resource. Our study not only provides a comprehensive descriptive information for future investigations on the diversity, functionality, and determinants of avian microbiomes, but also underscores the importance of microbial communities in broader ecological contexts.

Dynamics alteration of the gut microbiota and faecal metabolomes in very low or extremely low birth weight infants: a Chinese single-center, prospective cohort study.

The aim of this study is to comprehensively investigate the temporal dynamics of faecal gut microbiota and metabonomics in early postnatal with a focus on very low or extremely low birth weight (VLBW/ELBW) infants. We collected faecal samples from 157 VLBW/ELBW infants at three time points: days 1, 14, and 28 in a prospective cohort study. The faecal microbial diversity, abundance, composition, and metabolomic analyses were determined using 16S rRNA sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS). Microbiome functional analyses were conducted utilizing PICRUSt2. The ecological association networks were employed to investigate the interactions between gut microbiota and identify the core genus within 28 days of birth, as well as to unveil correlations between taxa and metabolites. (1) The alpha diversity of gut microbiota significantly decreased from D1 to D28, accompanied by an interrupted trajectory lacking obligate anaerobes. At the phylum level, the 16S RNA sequencing results showed an increase in Proteobacteria and a decrease in Firmicutes and Bacteroidota from D1 to D28. At the genus level, there was a decrease in the relative abundance of Staphylococcus, Acinetobacter and Ureaplasma, with Klebsiella and Enterococcus emerging as the most abundant genera. (2) The analysis revealed a total of 561 metabolic markers that exhibited significant and distinct alterations between D1 and D14. (3) Ecological association networks revealed that the gut microbiota in D1 exhibited a significantly higher degree of microbial interactions compared to those in D14 and D28. Additionally, Enterococcus, Klebsiella, and Enterobacter were major contributors to the co-occurring network at these three time points. (4) Steroid hormone biosynthesis, including tetrahydrocortisone, androsterone glucuronide, androstenedione and etiocholanolone glucuronide, decreased within 28 days after birth. We have successfully demonstrated a significant dysbiosis in the gut microbiota and a subsequent decrease in its diversity within 4 weeks postpartum in VLBW/ELBW infants. Monitoring the gut microbiota of VLBW/ELBW infants and promptly rectifying dysbiosis in the early stages may represent a potential therapeutic strategy.

Human milk oligosaccharides and milk fat globule membrane reduce allergic reactions in mice through the modulation of gut microbiota and metabolic functions.

Human milk oligosaccharides (HMOs) and the milk fat globule membrane (MFGM) represent novel treatments for cow's milk allergy (CMA). They exhibit the beneficial attribute of diminishing nutrient damage when compared to conventional enzymatic digestion of milk proteins. However, the effects and mechanisms underlying the synergistic interaction between HMOs and the MFGM in allergy treatment remain unclear. Consequently, this study was undertaken to assess the protective properties of HMOs and the MFGM against CMA and to elucidate their potential mechanisms in a mouse model of β-lactoglobulin (BLG)-induced allergy. The findings demonstrated that HMOs and the MFGM could significantly reduce the allergy score and splenic index, and they diminished the levels of inflammatory mediators (total immunoglobulin E (IgE), specific IgE, histamine, and mMCP-1), while concurrently bolstering tight junctions (ZO-1, claudin-1, and occludin), and reducing intestinal permeability. Notably, HMOs and the MFGM exhibited optimal synergy. In addition, HMOs and the MFGM synergistically mitigated the immune response to Th2 overactivity in allergy by the promotion of Th1 and Treg cell responses, thereby suppressing the levels of inflammatory cytokines IL-4 and IL-5. Analysis of the gut microbiota and its metabolic activities revealed that HMOs and the MFGM increased the abundance of Lactobacillus and Butyricicoccus, leading to higher production of butyrate. Furthermore, these beneficial bacteria and the resultant butyrate also contributed to the suppression of allergy-associated bacterial populations such as Desulfovibrio and Rikenellaceae. In summary, HMOs and the MFGM acted in synergy to modulate inflammatory responses and ameliorate barrier damage, contributing to the mitigation of CMA, a process potentially linked to gut microbiota dynamics and the resultant butyrate metabolism. This effect may be related to the gut microbiota and its metabolic production of butyrate.

Comparative analysis of pectin and prebiotics on human microbiota modulation in early life stages and adults.

The gut microbiota is essential in human health, influencing various physiological processes ranging from digestion and metabolism to immune function and mental health. Dietary fiber pectins and prebiotics have emerged as key modulators of gut microbiota composition and function, offering potential therapeutic implications for promoting gut health and preventing intestinal inflammatory diseases. In this review, we explore the modulation of gut microbiota by dietary fiber pectins and prebiotics in infants and adults. We begin with an overview of the gut microbiota composition and function in different age groups, highlighting the factors in shaping microbial communities in both age groups, especially the effect of diet. We then delve into the impact of dietary fiber pectins and prebiotics on gut microbiota composition and function, examining their effects on digestive health, intestinal barrier integrity, immune function, metabolic health, and mental health across different life stages. We further compare how aging affects the gut function and immune system, and we discuss the main health outcomes associated with dietary fiber intake and prebiotics, including the impact on digestive health, improvement in immune function, improvement in cholesterol and glucose metabolism, weight management, mental health, and prevention of diseases. Finally, we highlight the challenges and future directions for research. By advancing the understanding of gut microbiota dynamics and translating scientific insights into clinical practice, it could harness the full potential of dietary fiber pectins and prebiotics to optimize gut health, improve overall well-being across the lifespan, and increase longevity.

Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China.

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.

Exploiting fucoxanthin mono-carrier nanoparticles to modulate digestion and metabolic regulation in an obesity model

Fucoxanthin (FX), a natural compound derived from marine algae, and FX-based nanoparticles (FZ) were investigated for their potential in regulating glucose and lipid metabolism. Gavage interventions with FX, FZ, and zein hydrolysate (ZH) were administered to obese mice, resulting in significant outcomes. These interventions led to variations in growth rates, reduced blood glucose levels, improved lipid profiles, and ameliorated liver pathology. Our mRNA expression analysis revealed modulation of key genes involved in glucose metabolism. Gut analysis, including short-chain fatty acid detection and 16S rRNA gene sequencing, provided insights into gut microbiota modulation. Notably, differences observed in vivo between FX and FZ were attributed to their distinct release rates during in vitro digestion in the stomach and intestine. This comprehensive study validates our methods, modeling, and metabolic parameter determination, reinforcing the significance of our results. In conclusion, our findings highlight the promising potential of FX-encapsulated interventions in modulating metabolic pathways. Furthermore, they emphasize the crucial role of gut microbiota dynamics in the strategic mitigation of disorders associated with obesity.

Genetic analysis of the causal relationship between gut microbiota and intervertebral disc degeneration: a two-sample Mendelian randomized study

PurposeSeveral recent studies have reported a possible association between gut microbiota and intervertebral disc degeneration; however, no studies have shown a causal relationship between gut microbiota and disc degeneration. This study was dedicated to investigate the causal relationship between the gut microbiota and intervertebral disc degeneration and the presence of potentially bacterial traits using two-sample Mendelian randomization.MethodsA two-sample Mendelian randomization study was performed using the summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium. Summary statistics of intervertebral disc degeneration were obtained from the FinnGen consortium R8 release data. Five basic methods and MR-PRESSO were used to examine causal associations. The results of the study were used to examine the causal association between gut microbiota and intervertebral disc degeneration. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables.ResultsBy using Mendelian randomization analysis, 10 bacterial traits potentially associated with intervertebral disc degeneration were identified: genus Eubacterium coprostanoligenes group, genus Lachnoclostridium, unknown genus id.2755, genus Marvinbryantia, genus Ruminococcaceae UCG003, family Rhodospirillaceae, unknown genus id.959, order Rhodospirillales, genus Lachnospiraceae NK4A136 grou, genus Eubacterium brachy group.ConclusionThis Mendelian Randomization study found a causal effect between 10 gut microbiota and intervertebral disc degeneration, and we summarize the possible mechanisms of action in the context of existing studies. However, additional research is essential to fully understand the contribution of genetic factors to the dynamics of gut microbiota and its impact on disc degeneration.

Disentangling the age-related manner in the associations between gut microbiome and women’s health: a multi-cohort microbiome study

ABSTRACT Women’s health encompasses life-course healthcare, and mounting evidence emphasizes the pivotal contribution of gut microbiota. Therefore, understanding the temporal dynamics of gut microbiota and how age influences disease-gut microbiota associations is essential for improving women’s health. By analyzing metagenomic data from 3625 healthy women, we revealed significant effects of age on gut microbiota and age-dependent patterns in microbial features, such as relative abundance, Shannon index, and microbial network properties. Additionally, declining trends in the predictive accuracy of gut microbiota for age groups were shown using iterative sub-sampling based random forest (ISSRF) model. Age-specific species markers were also identified, many of which were shared across age groups. To investigate the influence of age on disease-gut microbiota associations, metagenomic data from 681 women with various disease conditions and 491 matched healthy controls were collected. A substantial proportion of species markers for inflammatory bowel disease (IBD), type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ACVD), and impaired glucose tolerance (IGT) differed in relative abundance across age groups, and were also age-specific species markers. Besides, the microbiota-based probabilities of IBD and ACVD were positively correlated with age. Furthermore, the age specificity of disease-gut microbiota associations was explored using the ISSRF model. Associations between IBD and gut microbiota were age-specific, with reduced stability of disease species markers in childhood and adolescence, possibly due to decrease in the effect size between patients and controls. Our findings provided valuable insights into promoting healthy aging and developing personalized healthcare strategies for women.

Glycerol and reuterin-producing Limosilactobacillus reuteri enhance butyrate production and inhibit Enterobacteriaceae in broiler chicken cecal microbiota PolyFermS model

BackgroundAdministering probiotic strains of Limosilactobacillus reuteri to poultry has been shown to improve poultry performance and health. Some strains of L. reuteri taxa can produce reuterin, a broad-spectrum antimicrobial compound from glycerol conversion, with high inhibitory activity against enterobacteria. However, little is known about the metabolism of glycerol in the complex chicken cecal microbiota nor the effect of glycerol, either alone or combined with L. reuteri on the microbiota. In this study, we investigated the effect of L. reuteri PTA5_F13, a high-reuterin-producing chicken strain and glycerol, alone or combined, on broiler chicken cecal microbiota composition and activity using the continuous PolyFermS model recently developed to mimic chicken cecal fermentation.MethodsThree independent PolyFermS chicken cecal microbiota models were inoculated with immobilized cecal microbiota from different animals and operated continuously. The effects of two additional levels of glycerol (50 and 100 mM) with or without daily supplementation of chicken-derived L. reuteri PTA5_F13 (107 CFU/mL final concentration) were tested in parallel second-stage reactors continuously inoculated with the same microbiota. We analyzed the complex chicken gut microbiota structure and dynamics upon treatment using 16S rRNA metabarcoding and qPCR. Microbiota metabolites, short-chain and branched-chain fatty acids, and glycerol and reuterin products were analyzed by HPLC in effluent samples from stabilized reactors.ResultsSupplementation with 100 mM glycerol alone and combined with L. reuteri PTA5_F13 resulted in a reproducible increase in butyrate production in the three modelled microbiota (increases of 18 to 25%). Glycerol alone resulted also in a reduction of Enterobacteriaceae in two of the three microbiota, but no effect was detected for L. reuteri alone. When both treatments were combined, all microbiota quantitatively inhibited Enterobacteriaceae, including in the last model that had very high initial concentrations of Enterobacteriaceae. Furthermore, a significant 1,3-PDO accumulation was measured in the effluent of the combined treatment, confirming the conversion of glycerol via the reuterin pathway. Glycerol supplementation, independent of L. reuteri addition, did not affect the microbial community diversity.ConclusionsGlycerol induced a stable and reproducible butyrogenic activity for all tested microbiota and induced an inhibitory effect against Enterobacteriaceae that was strengthened when reuterin-producing L. reuteri was spiked daily. Our in vitro study suggests that co-application of L. reuteri PTA5_F13 and glycerol could be a useful approach to promote chicken gut health by enhancing metabolism and protection against Enterobacteriaceae.

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity.

Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP-R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP-R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP-R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP-R groups. The HC group and BP-R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP-R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects.

Feeding and water temperature modulate the potential activity of gut microbiota in greater amberjack juveniles (Seriola dumerili)

Gut microbial communities are highly dynamic and respond to factors such as diet and host metabolism. However, there is limited knowledge on changes in gut microbiota during the daily cycle. To investigate how interactions between feeding and water temperature affected the diurnal dynamics and activity of the microbiota, we analyzed the qualitative and quantitative composition in feces of the potentially active bacterial community along a day cycle in greater amberjack juveniles (Seriola dumerili). Bacterial density (based on qPCR of 16S rDNA) in feces was relatively stable along the day. In contrast bacterial activity (based on qPCR of 16S rRNA) increased during the period of active feeding, and was reduced to pre-feeding levels four hours after the last meal. The relative potential activity of the bacterial community in fish feces varied with postprandial time. At the phylum level there was a shift from a Spirochaetes-dominated community in the morning to increased potential activity of Proteobacteria after feeding. At lower taxonomic level, i.e. order, the bacterial community was dominated by Mycoplasmoidales, which relative potential activity was maintained throughout the day in all treatments. By contrast, for absolute potential bacterial activity at the order level there was a peak in potential activity of several bacterial orders at 6h after first feeding, with the most noticeable increase observed for Mycoplasmoidales. Results from the present work also indicated a close relation between the effect of water temperature and microbial dynamics. This is the first study assessing the quantitative and qualitative effects of water temperature and daily feeding rhythm on the gut microbiota dynamics in fish. Feeding was the main driver modulating bacterial activity, promoting a peak in bacterial activity 6h after first feeding. However, water temperature also modulated gut microbiota dynamics, with a marked effect on the time scale. In addition, results indicate that analysis of absolute bacterial potential activity provides a better resolution of metabolically active gut microbial community, since a change in the absolute activity of a single taxon can alter the relative activity of all taxa.

Gut, oral, and nasopharyngeal microbiota dynamics in the clinical course of hospitalized infants with respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once. Here, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing. Interestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals. Monitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.

Gut microbiota and transcriptome dynamics in every-other-day fasting are associated with neuroprotection in rats with spinal cord injury.

Every-other-day fasting (EODF) is a classical intermittent fasting (IF) mode with neuroprotective effects that promotes motor function recovery after spinal cord injury (SCI) in rats. However, its dynamic effects on the gut microbiota and spinal cord transcriptome remain unknown. In this study, 16S rRNA sequencing and RNA-seq analysis were used to investigate the effects of ad libitum (AL) and EODF dietary modes on the structural characteristics of rat gut microbiota in rats and the spinal cord transcriptome at various time points after SCI induction. Our results showed that both dietary modes affected the bacterial community composition in SCI rats, with EODF treatment inducing and suppressing dynamic changes in the abundances of potentially anti-inflammatory and pro-inflammatory bacteria. Furthermore, the differentially expressed genes (DEGs) enriched after EODF intervention in SCI rats were associated with various biological events, including immune inflammatory response, cell differentiation, protein modification, neural growth, and apoptosis. In particular, significant spatiotemporal differences were apparent in the DEGs associated with neuroprotection between the EODF and AL interventions. These DGEs were mainly focused on days 1, 3, and 7 after SCI. The relative abundance of certain genera was significantly correlated with DEGs associated with neuroprotective effects in the EODF-SCI group. Our results showed that EODF treatment may exert neuroprotective effects by modulating the transcriptome expression profile following SCI in rats. Furthermore, gut microbiota may be partially involved in mediating these effects.

A health-promoting role of exclusive breastfeeding on infants through restoring delivery mode-induced gut microbiota perturbations.

The establishment of human gut microbiota in early life is closely associated with both short- and long-term infant health. Delivery mode and feeding pattern are two important determinants of infant gut microbiota. In this longitudinal cohort study, we examined the interplay between the delivery mode and feeding pattern on the dynamics of infant gut microbiota from 6 weeks to 6 months post-delivery in 139 infants. We also assessed the relationship between infant respiratory infection susceptibility and gut microbial changes associated with delivery mode and feeding pattern. At 6 weeks postpartum, the composition and structure of gut microbiota of cesarean section-delivered (CSD) infants differed from those of vaginally delivered (VD) infants, with decreased Bacteroides and Escherichia-Shigella and increased Klebsiella, Veillonella, and Enterococcus. At 6 months postpartum, these delivery mode-induced microbial shifts were restored by exclusive breastfeeding, resulting in similar gut microbial profiles between VD and CSD infants who were exclusively breastfed (P = 0.57) and more variable gut microbial profiles between VD and CSD infants who were mixed fed (P < 0.001). We identified that the VD-associated genera were enriched in healthy infants, while the CSD-associated genera were enriched in infants who suffered from respiratory infections. Our findings indicate that exclusive breastfeeding may play a health-promoting role by reducing infant respiratory infection susceptibility through the restoration of gut microbiota perturbations caused by cesarean section.

Population Dynamics of Intestinal Enterococcus Modulate Galleria mellonella Metamorphosis.

Microbes found in the digestive tracts of insects are known to play an important role in their host's behavior. Although Lepidoptera is one of the most varied insect orders, the link between microbial symbiosis and host development is still poorly understood. In particular, little is known about the role of gut bacteria in metamorphosis. Here, we explored gut microbial biodiversity throughout the life cycle of Galleria mellonella, using amplicon pyrosequencing with the V1 to V3 regions, and found that Enterococcus spp. were abundant in larvae, while Enterobacter spp. were predominant in pupae. Interestingly, eradication of Enterococcus spp. from the digestive system accelerated the larval-to-pupal transition. Furthermore, host transcriptome analysis demonstrated that immune response genes were upregulated in pupae, whereas hormone genes were upregulated in larvae. In particular, regulation of antimicrobial peptide production in the host gut correlated with developmental stage. Certain antimicrobial peptides inhibited the growth of Enterococcus innesii, a dominant bacterial species in the gut of G. mellonella larvae. Our study highlights the importance of gut microbiota dynamics on metamorphosis as a consequence of the active secretion of antimicrobial peptides in the G. mellonella gut. IMPORTANCE First, we demonstrated that the presence of Enterococcus spp. is a driving force for insect metamorphosis. RNA sequencing and peptide production subsequently revealed that antimicrobial peptides targeted against microorganisms in the gut of Galleria mellonella (wax moth) did not kill Enterobacteria species, but did kill Enterococcus species, when the moth was at a certain stage of growth, and this promoted moth pupation.

Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer

Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.

#4941 A METABOLOMIC FINGERPRINT PERSPECTIVE OF GUT-DERIVED METABOLITES ON EARLY DIABETIC KIDNEY DISEASE IN TYPE 2 DIABETES MELLITUS PATIENTS

Abstract Background and Aims Type 2 diabetes mellitus (T2DM) is the first cause of end stage renal disease worldwide. Metabolite profiling is an emerging field of great significance, as T2DM prevalence is continuously rising. The subtle dynamics of gut microbiota derived metabolites may have important implications in diabetic kidney disease (DKD) development. Nitrogen metabolic pathway and retinoic acid signaling pathway seem to be involved in early pathogenic mechanisms of DKD. The aim of study was to discover new putative gut-derived biomarkers that interfere with early physio-pathological mechanisms in DKD, regarding the podocyte, tubule, and the renal endothelium. Method The serum and urine of 90 T2DM patients (P group) and 20 healthy subjects (C group), were assessed in a cross-sectional study, by ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques. P group was divided in 3 subgroups (normoalbuminuria-P1, microalbuminuria-P2, macroalbuminuria-P3). Statistical analysis was performed by untargeted multivariate (PLSDA, VIP scores, Random Forest, Biomarker analysis) and univariate (One Way ANOVA, Biomarker Analysis) methods. Results Multivariate analysis, by which the P group vs. C group were compared, displayed: (1) in serum samples: increased levels (P&amp;gt;C) of all-trans retinoic acid, cysteine-S sulfate, oleoylglicine, threonylglycine and decreased levels (P&amp;lt;C) of phenylalanine, tyrosine, kynurenic acid; (2) in urine samples, there were increased levels of: all-trans retinoic acid, indoxyl suflate, serotonin sulfate and glycylprolylarginine. Subsequently, by applying univariate analysis, the biomarkers derived from gut microbiota were selected: (1) in serum: all-trans retinoic acid (C&amp;lt;P1&amp;lt;P2&amp;lt;3), phenylalanine, tyrosine, and kynurenic acid with levels decreasing progressively from C to P1-P2-P3 (2) in urine: all trans retinoic acid, indoxyl sulfate, and serotonin sulfate, showing good differentiation between C and P1, and slight differences between P1∼P2∼P3 subgroups. The study suggests that ATRAs dynamic is disturbed in the normoalbuminuric stage of DKD. While its urinary levels correlated significantly with albuminuria, the changes observed in P1 subgroup, in serum and urine, may be correlated to the loss of renal tubular tight junction as a result of claudin downregulation. Phenylalanine and tyrosine, a part of nitrogen metabolic pathway, are indicators of the new-onset DKD. Their levels were upregulated in serum vs. urine, indicating their possible involvement in early DKD when comparing C vs. P1-P2-P3. Kynurenic acid and indoxyl-sulfate result from tryptophan metabolism. Low levels in serum of kynurenic acid may suggest its possible implication in incipient endothelial dysfunction in DKD. Indoxyl-sulfate (IS) urinary excretion is dependent on albuminuria. The study shows an elevated excretion of IS, in the normoalbuminuric group compared to controls and may suggest a tubular damage that precedes the glomerular modifications in DKD. Conclusion UHPLC-QTOF-ESI+-MS untargeted analysis reveals a particular metabolite fingerprint in early DKD. The study describes all-trans retinoic acid, phenylalanine, tyrosine, kynurenic acid, and indoxyl sulfate, as potential key biomarkers involved in early DKD pathogenesis, their levels being expressed in P1 subgroup compared with C group, and P2, P3 subgroups.

Temporal Variations in the Gut Microbiota of the Globally Endangered Sichuan Partridge (Arborophila rufipectus): Implications for Adaptation to Seasonal Dietary Change and Conservation.

Host-associated microbiotas are known to influence host health by aiding digestion, metabolism, nutrition, physiology, immune function, and pathogen resistance. Although an increasing number of studies have investigated the avian microbiome, there is a lack of research on the gut microbiotas of wild birds, especially endangered pheasants. Owing to the difficulty of characterizing the dynamics of dietary composition, especially in omnivores, how the gut microbiotas of birds respond to seasonal dietary changes remains poorly understood. The Sichuan partridge (Arborophila rufipectus) is an endangered pheasant species with a small population endemic to the mountains of southwest China. Here, 16S rRNA sequencing and Tax4Fun were used to characterize and compare community structure and functions of the gut microbiota in the Sichuan partridges across three critical periods of their annual life cycle (breeding, postbreeding wandering, and overwintering). We found that the microbial communities were dominated by Firmicutes, Proteobacteria, Actinobacteria, and Cyanobacteria throughout the year. Diversity of the gut microbiotas was highest during postbreeding wandering and lowest during the overwintering periods. Seasonal dietary changes and reassembly of the gut microbial community occurred consistently. Composition, diversity, and functions of the gut microbiota exhibited diet-associated variations, which might facilitate host adaptation to diverse diets in response to environmental shifts. Moreover, 28 potential pathogenic genera were detected, and their composition differed significantly between the three periods. Investigation of the wild bird gut microbiota dynamics has enhanced our understanding of diet-microbiota associations over the annual life cycle of birds, aiding in the integrative conservation of this endangered bird. IMPORTANCE Characterizing the gut microbiotas of wild birds across seasons will shed light on their annual life cycle. Due to sampling difficulties and the lack of detailed dietary information, studies on how the gut microbiota adapts to seasonal dietary changes of wild birds are scarce. Based on more detailed dietary composition, we found a seasonal reshaping pattern of the gut microbiota of Sichuan partridges corresponding to their seasonal dietary changes. The variation in diet and gut microbiota potentially facilitated the diversity of dietary niches of this endangered pheasant, revealing a seasonal diet-microbiota association across the three periods of the annual cycle. In addition, identifying a variety of potentially pathogenic bacterial genera aids in managing the health and improving survival of Sichuan partridges. Incorporation of microbiome research in the conservation of endangered species contributes to our comprehensive understanding the diet-host-microbiota relationship in wild birds and refinement of conservation practices.