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The potential health impact of exposure to anthropogenic chemicals has raised major concerns worldwide. Phthalates are mainly used in the plastic industry and have been associated with adverse effects in humans. Di-n-butyl phthalate (DBP) is one of the dominant phthalates with a ubiquitous presence in the environment. While many studies have examined the endocrine disrupting properties of DBP, with a focus on developmental and reproductive dysfunctions, studies of its effects on the adult reproductive system and gut microbiota are limited. This thesis aimed to determine persistent effects of DBP on the adult male reproductive system, provide a high-throughput screening tool for identifying reproductive toxicants, and characterize the effects of DBP on the gut microbiota. Paper I investigated if adult DBP exposure can induce persistent effects on the mature reproductive system. Adult male mice were orally exposed to 10 or 100 mg/kg/day for five weeks and testes were collected one week after the last dose. The results demonstrated a significant decrease in testosterone levels in the DBP-exposed groups. Mechanistically, the levels of steroidogenic enzymes, cell-specific markers and oxidative stress were increased. In paper II, elements of the in vivo testicular microenvironment, including functional testosterone production, were modeled using a three-dimensional (3D) heterogenous testicular cell co-culture derived from neonatal mice. Automated high-content imaging of cell-specific markers confirmed the presence of germ cells (DAZL+), Leydig cells (CYP11A1+), and Sertoli cells (SOX9+). DBP exposure decreased testosterone production, as well as levels of the steroidogenic enzyme CYP11A1, and the steroidogenic regulator StAR. Overall, this in vitro 3D model recapitulates the testicular pathways involved in DBP toxicity, making it a relevant tool for assessing reprotoxic effects of chemicals. Paper III investigated the impact of oral DBP exposure on the gut microbiot

Food allergy has become a major public health problem all over the world. Evidence showed that allergic reactions induced by food proteins often lead to disturbances in the gut microbiota (symbiotic bacteria). Gut microbiota plays an important role in maintaining the balance between intestinal immune tolerance and allergic reactions. Dietary intervention has gradually become an important method for the prevention and treatment of allergic diseases, and changing the composition of gut microbiota through oral intake of prebiotics and probiotics may serve as a new effective adjuvant treatment measure for allergic diseases. In this paper, the main mechanism of food allergy based on intestinal immunity was described firstly. Then, the clinical and experimental evidence showed that different prebiotics and probiotics affect food allergy by changing the structure and composition of gut microbiota was summarized. Moreover, the molecular mechanism in which the gut microbiota and their metabolites may directly or indirectly regulate the immune system or intestinal epithelial barrier function to affect food immune tolerance of host were also reviewed to help in the development of food allergy prevention and treatment strategies based on prebiotics and probiotics.

Plant derived dietary polysaccharides are important for gut health and have the potential to modulate the gut microbial community. Dietary rhamnogalacturonan-I obtained by enzymatic treatment of carrot pomace has shown prebiotic properties. In the present study, fermentability of carrot rhamnogalacturonan-I (cRG-I) by faecal microbiota of four donors was studied in an adapted M-SHIME® intestinal model. Despite its complex structure, cRG-I was degraded rapidly in the proximal colon compartment and fermentation became quicker and more complete during three weeks of repeated supplementation. Tracking the change in the molecular weight distribution pattern of cRG-I during the supplementation showed two main donor-dependent gut microbial fermentation strategies designated as either the general or preferential pathway. In the general fermentation pathway, different cRG-I structures were hydrolysed concomitantly, while in the preferential pathway discrete structures were sequentially fermented in a selective manner. Especially arabinan sidechains were utilized before the RG-I backbone, which correlated with an increase in Bifidobacterium longum absolute abundance over the three weeks period. MALDI-TOF MS confirmed that arabinan-, galactan- and arabinogalactan-sidechains were first to be released and degraded. Donor specific production of all SCFA increased over time with a general trend of higher levels of acetate and propionate than butyrate. Strikingly, although the host's baseline gut microbiota composition led to distinct cRG-I hydrolysis routes, the final RG-I consumption was almost complete for both routes, leading to similar metabolic profiles at the end of the three weeks treatment period.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitneys test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p < .05) and included impo

Pregnancy alters many physiological systems, including the maternal gut microbiota. Diet is a key regulator of this system and can alter the host immune system to promote inflammation. Multiple perinatal disorders have been associated with inflammation, maternal metabolic alterations, and gut microbial dysbiosis, including gestational diabetes mellitus, pre-eclampsia, preterm birth, and mood disorders. However, the effects of high-inflammatory diets on the gut microbiota during pregnancy have yet to be fully explored. We aimed to address this gap using a system-based approach to characterize associations among dietary inflammatory potential, a measure of diet quality, and the gut microbiome during pregnancy. Forty-seven pregnant persons were recruited prior to 16 weeks of gestation. Participants completed a food frequency questionnaire (FFQ) and provided fecal samples. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) from the FFQ data. Fecal samples were analyzed using 16S rRNA amplicon sequencing. Differential taxon abundances with respect to the DII score were identified, and the microbial metabolic potential was predicted using PICRUSt2. Inflammatory diets were associated with decreased vitamin and mineral intake and a dysbiotic gut microbiota structure and predicted metabolism. Gut microbial compositional differences revealed a decrease in short-chain fatty acid producers such as Faecalibacterium, and an increase in predicted vitamin B12 synthesis, methylglyoxal detoxification, galactose metabolism, and multidrug efflux systems in pregnant individuals with increased DII scores. Dietary inflammatory potential was associated with a reduction in the consumption of vitamins and minerals and predicted gut microbiota metabolic dysregulation.

Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N6-methyladenosine (m6A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m6A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m6A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m6A epitranscriptome in multiple tissues. Mechanistically, the expression of m6A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m6A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m6A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.

Early-life nutrition significantly impacts neonatal health and development, where nutrient deficiencies or excesses can lead to various health complications. This is particularly true for iron nutrition. Exclusively breast-fed infants are susceptible to iron deficiency, prompting the use of iron-fortified diets. However, excessive iron exposure poses risks, including disruption of the gut microbiome. We investigated the complex interactions between dietary iron levels, gut microbiota, and specific dietary interventions in neonatal and pathogenic Escherichia coli (E. coli)-challenged weaned pigs, offering insights applicable to both animal and human health and nutrition.Using a piglet model as a translational model for human infants, we explored the impact of high iron fortification and inulin or synbiotic supplementation on iron homeostasis and trace mineral bioavailability to better understand the biological functions of iron, the regulation of iron homeostasis, and the health consequences of iron imbalance in early infancy. Twenty-four piglets were randomly assigned to four treatments, receiving either iron-adequate milk (AI), high-iron milk (HI), HI milk with 5% inulin (HIP), or HIP milk with an oral gavage of Ligilactobacillus agilis YZ050 (HIS). The study revealed that HI fortification increased hemoglobin (Hb), hematocrit (Hct), and serum iron levels but also caused hepatic tissue iron deposition and concurrently reduced zinc (Zn) and copper (Cu) absorption. Inulin supplementation in HIP and HIS diets attenuated hepatic iron overload and decreased colonic and fecal iron levels, suggesting that inulin has the potential to modulate systemic iron utilization and mitigate some of the adverse effects of excessive iron fortification. Further analysis focused on the impact of iron fortification and inulin supplementation, with or without Ligilactobacillus agilis YZ050 (L. agilis YZ050), on the gut microbiome of piglets. Using 16S rRNA sequencing, the study found that

Colorectal cancer (CRC), the third most common cancer globally, has shown links to disturbed gut microbiota. While significant efforts have been made to establish a microbial signature indicative of CRC using shotgun metagenomic sequencing, the challenge lies in validating this signature with 16S ribosomal RNA (16S) gene sequencing. The primary obstacle is reconciling the differing outputs of these two methodologies, which often lead to divergent statistical models and conclusions. In this study, we introduce an algorithm designed to bridge this gap by mapping shotgun-derived taxa to their 16S counterparts. This mapping enables us to assess the predictive performance of a shotgun-based microbiome signature using 16S data. Our results demonstrate a reduction in performance when applying the 16S-mapped taxa in the shotgun prediction model, though it retains statistical significance. This suggests that while an exact match between shotgun and 16S data may not yet be feasible, our approach provides a viable method for comparative analysis and validation in the context of CRC-associated microbiome research, This research was funded by Instituto de Salud Carlos III, co-funded by FEDER funds–a way to build Europe–grants PI17-00092 and PI20-01439; Spanish Association Against Cancer (AECC) Scientific Foundation—grant GCTRA18022MORE; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) action Genrisk. E.R. has funding from Fundació Marató TV3—grant 875/C/2021. D.B-C. is supported by Instituto de Salud Carlos III Sara Borrell—grant CD21/00094. O.K-L is supported by the Formación de profesorado universitario (FPU) program from the Spanish Ministerio de Universidades—grant FPU2020-02907. T.G. group acknowledges support from the Spanish Ministry of Science and Innovation for grants PID2021-126067NB-I00, CPP2021-008552, PCI2022-135066-2, and PDC2022-133266-I00, cofounded by ERDF “A way of making Europe”; from the Catalan Research Agency (AGAUR) SGR01551; from the European Union’s Horizon 2020 research and innovation programme (ERC-2016-724173); from the Gordon and Betty Moore Foundation (Grant GBMF9742); from the “La Caixa” foundation (Grant LCF/PR/HR21/00737), and from the Instituto de Salud Carlos III (IMPACT Grant IMP/00019 and CIBERINFEC CB21/13/00061—ISCIII-SGEFI/ERDF). Sample collection of this work was supported by the Plataforma Biobancos (PT17/0015/0024) and ICOBIOBANC, sponsored by the Catalan Institute of Oncology., Peer Reviewed, "Article signat per 12 autors/es: Elies Ramon, Mireia Obón-Santacana, Olfat Khannous-Lleiffe, Ester Saus,Toni Gabaldón, Elisabet Guinó, David Bars-Cortina, Gemma Ibáñez-Sanz, Lorena Rodríguez-Alonso, Alfredo Mata, Ana García-Rodrígue and Victor Moreno ", Postprint (published version)

Growing evidence suggests a close relationship between gut microbiota and infectious diseases. However, the specific role of gut microbiota in host-pathogen interactions during aquaculture-related infections remains poorly understood. This study investigated the diversity and composition of gut microbiota communities in Aeromonas veronii-infected Lateolabrax maculatus using high-throughput sequencing. The results revealed significant changes in the structure and composition of L. maculatus gut microbiota after A. veronii infection. Over time, Bacteroidetes and Firmicutes decreased significantly, while Proteobacteria increased significantly after A. veronii infection. Most intestinal bacteria showed a decline in abundance over time, with probiotics (such as Lactobacillus) experiencing a significant decrease and pathogens (such as Aeromonas) showing a significant increase. Conversely, no differences were observed in the structure and composition of gut microbiota between healthy L. maculatus and those infected with A. veronii after treatment with Lactobacillus plantarum; no changes in relative abundances of other bacterial phyla or genera except for Aeromonas. Furthermore, intestinal flora's structural diversity and composition differed significantly from untreated L. maculatus infected with A. veronii. These findings suggest alterations in the structure and composition of gut microbiota following A. veronii infection. L. plantarum can maintain a dynamic balance within the intestinal flora, reducing the potential risk of pathogen infections.

Antibiotic use and its abeyant effect on gut microbiota dysbiosis are key issues for Iraqi children's immune function. The equilibrium of gut microbiota is vital for immune system modulation, the development of a strong defense adjoin infections, and the abstention of autoimmune diseases. Misuse or inappropriate use of antibiotics, which is usually acquired by factors such as infections repetition or cultural practices, can agitate this antithesis and aftereffect in dysbiosis. The aim of this investigation is to acquisition out how frequently antibiotics are acclimated in Iraqi children and whether this use is associated to abnormalities in their gut microbiome. We additionally aim to investigate how these disturbances may aftereffect these children's allowed function. Materials and Methods: 70 Iraqi child in age range (2-8) have been involved in cross sectional study to assess the effect of antibiotics on both gut dysbiosis and immune. Results: This study shows that the sample has a gender imbalance, with more women than men, and modest age variety. Of the total population, 55.72% live in cities, 88.57% report having no health issues, with asthma being the most common at 5.71%. The frequency of antibiotic usage has a major effect on gut bacteria; higher use is associated with fewer helpful species and more dangerous ones.

Antibiotic use and its abeyant effect on gut microbiota dysbiosis are key issues for Iraqi children's immune function. The equilibrium of gut microbiota is vital for immune system modulation, the development of a strong defense adjoin infections, and the abstention of autoimmune diseases. Misuse or inappropriate use of antibiotics, which is usually acquired by factors such as infections repetition or cultural practices, can agitate this antithesis and aftereffect in dysbiosis. The aim of this investigation is to acquisition out how frequently antibiotics are acclimated in Iraqi children and whether this use is associated to abnormalities in their gut microbiome. We additionally aim to investigate how these disturbances may aftereffect these children's allowed function. Materials and Methods: 70 Iraqi child in age range (2-8) have been involved in cross sectional study to assess the effect of antibiotics on both gut dysbiosis and immune. Results: This study shows that the sample has a gender imbalance, with more women than men, and modest age variety. Of the total population, 55.72% live in cities, 88.57% report having no health issues, with asthma being the most common at 5.71%. The frequency of antibiotic usage has a major effect on gut bacteria; higher use is associated with fewer helpful species and more dangerous ones.

Background: Functional constipation (FC) in children is a common gastrointestinal disorder with a worldwide-pooled prevalence of 9.5%. Complaints include infrequent bowel movements, painful defecation due to hard and/or large stools, faecal incontinence, and abdominal pain. Prebiotic oligosaccharides have been shown to relieve constipation symptoms in young adults and elderly. However, sufficient evidence is lacking linking additional prebiotic intake to improve symptoms in children with FC. We hypothesise that prebiotic oligosaccharides are able to relieve symptoms of constipation in young children as well. Methods: In the present randomised, double-blind, placebo-controlled, multi-centre study, we will study the effects of two prebiotic oligosaccharides in comparison to placebo on constipation symptoms in children of 1–5 years (12 to 72 months) of age diagnosed with FC according to the Rome IV criteria for functional gastrointestinal disorders. The primary outcome measure will be change in stool consistency. Secondary outcomes include stool frequency and stool consistency in a number of cases (%). Tertiary outcomes include among others painful defecation, use of rescue medication, and quality of life. In addition, the impact on gut microbiome outcomes such as faecal microbiota composition and metabolites will be investigated. Participants start with a run-in period, after which they will receive supplements delivered in tins with scoops for 8 weeks, containing one of the two prebiotic oligosaccharides or placebo, followed by a 4-week wash-out period. Discussion: This randomised double-blind, placebo-controlled multi-centre study will investigate the effectiveness of prebiotic oligosaccharides in children aged 1–5 years with FC. Trial registration: ClinicalTrials.gov NCT04282551. Registered on 24 February 2020.

This work implemented a non-invasive volatile organic compounds (VOCs) monitoring approach to study how food components are metabolised by the gut microbiota in-vitro. The fermentability of a model food matrix rich in dietary fibre (oat bran), and a pure prebiotic (inulin), added to a minimal gut medium was compared by looking at global changes in the volatilome. The substrates were incubated with a stabilised human faecal inoculum over a 24-h period, and VOCs were monitored without interfering with biological processes. The fermentation was performed in nitrogen-filled vials, with controlled temperature, and tracked by automated headspace-solid-phase microextraction coupled with gas chromatography–mass spectrometry. To understand the molecular patterns over time, we applied a multivariate longitudinal statistical framework: repeated measurements—ANOVA simultaneous component analysis. The methodology was able to discriminate the studied groups by looking at VOCs temporal profiles. The volatilome showed a time-dependency that was more distinct after 12 h. Short to medium-chain fatty acids showed increased peak intensities, mainly for oat bran and for inulin, but with different kinetics. At the same time, alcohols, aldehydes, and esters showed distinct trends with discriminatory power. The proposed approach can be applied to study the intertwined pathways of gut microbiota food components interaction in-vitro.

Aim: The cell matrix of plant foods has received little attention in prebiotic fiber research. We aimed to understand the impact of the plant cell matrix in dried chicory root on its breakdown in the human gut to explain its reported beneficial effects on gut and metabolic health. Methods: We applied in vitro digestion and fermentation models together with an ex vivo gut barrier integrity model. Plant cell matrix intactness in the upper gastrointestinal tract was investigated by scanning electron microscopy. Colonic breakdown of inulin, and chicory root cubes and powder was assessed by gut microbiota analysis using 16S rRNA gene amplicon sequencing and determining the kinetics of changes in pH, gas, and short-chain fatty acid (SCFA) production. Finally, effects on gut barrier integrity were explored by exposing colonic biopsies to fermentation supernatants in an Ussing chamber model. Results: The plant cell matrix of dried chicory root cubes remained intact throughout upper gastrointestinal transit. Dried chicory root fermentation resulted in higher final relative abundances of pectin-degrading Monoglobus and butyrate-producing Roseburia spp. compared to inulin and a seven-fold increase in Bifidobacterium spp. in donors where these species were present. Dried chicory root cubes yielded similar total SCFAs but higher final butyrate levels than chicory root powder or isolated inulin with less gas produced. No uniform but donor-specific effects of fermentation supernatants on the maintenance of gut barrier integrity were detected. Conclusion: The intact plant cell matrix of dried chicory root affected its colonic breakdown kinetics and microbiota, underpinning its beneficial effect in vivo.

The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus, it plays a vital role in the host's health. Our understanding of the effect of the gut microbiome on health and disease has grown substantially over the past decades, mostly because of recent advances in sequencing and other high-throughput technologies. Given its high metabolic potential, proximity to the intestinal mucosa, and interaction with the immune system, it is not surprising that the gut microbiome is an important partaker of human health. Evidence of the importance of the gut microbiome in human health and disease is the growing number of conditions now linked to changes in the resident gut microbiota, including recurrent Clostridium difficile infections, inflammatory bowel disease, irritable bowel syndrome, colorectal cancer, allergies, neurological diseases, and metabolic diseases. Research into this field of the association of the gut microbiome with health and disease continues to expand at a rapid pace as we come to accept the gut microbiome as our “second genome.” Targeting the gut microbiome to restore/modulate its composition with the use of antibiotics, probiotics, prebiotics, and even fecal microbiota transplantation is considered a promising future strategy for the development of new solutions in the treatment of various diseases associated with an imbalance in microbiota composition and functioning.

Plant derived dietary polysaccharides are important for gut health and have the potential to modulate the gut microbial community. Dietary rhamnogalacturonan-I obtained by enzymatic treatment of carrot pomace has shown prebiotic properties. In the present study, fermentability of carrot rhamnogalacturonan-I (cRG-I) by faecal microbiota of four donors was studied in an adapted M-SHIME® intestinal model. Despite its complex structure, cRG-I was degraded rapidly in the proximal colon compartment and fermentation became quicker and more complete during three weeks of repeated supplementation. Tracking the change in the molecular weight distribution pattern of cRG-I during the supplementation showed two main donor-dependent gut microbial fermentation strategies designated as either the general or preferential pathway. In the general fermentation pathway, different cRG-I structures were hydrolysed concomitantly, while in the preferential pathway discrete structures were sequentially fermented in a selective manner. Especially arabinan sidechains were utilized before the RG-I backbone, which correlated with an increase in Bifidobacterium longum absolute abundance over the three weeks period. MALDI-TOF MS confirmed that arabinan-, galactan- and arabinogalactan-sidechains were first to be released and degraded. Donor specific production of all SCFA increased over time with a general trend of higher levels of acetate and propionate than butyrate. Strikingly, although the host's baseline gut microbiota composition led to distinct cRG-I hydrolysis routes, the final RG-I consumption was almost complete for both routes, leading to similar metabolic profiles at the end of the three weeks treatment period.

Aims: Chronic kidney disease (CKD) represents a global health concern, disproportionately affecting the elderly with heightened cardiovascular risk. The emerging focus on the gut microbiota's role in CKD pathophysiology represents a pivotal area in nephrology; however, the evidence on this topic is limited. This observational prospective study, in the framework of the PREDIMED-Plus trial, investigates associations between gut microbiota composition and the 1-year trajectory of CKD in 343 participants aged 55–75 years with high cardiovascular risk. Materials and methods: Kidney function was assessed at baseline and at 1-year of follow-up through the estimated glomerular filtration rate based on cystatin C (eGFR-CysC) and CKD defined by eGFR-CysC <60 mL/min/1.73 m2. Participants were grouped based on their 1-year CKD trajectory: Group 1 maintained normal status or improved from CKD to normal, while Group 2 maintained CKD or worsened from normal to CKD. Fecal microbiota composition was assessed through 16S sequencing. Key findings: We observed differences in gut microbiota composition between CKD trajectory groups. Notably, the baseline relative abundance of Lachnoclostridium and Lachnospira, both butyrate-producing genera, was lower in participants maintaining or progressing to CKD. Longitudinally, a decrease in Lachnospira abundance was associated with CKD progression. The improved Chao1 index after 1-year follow-up suggests a link between enhanced microbial richness and stable/better kidney function. Significance: The findings underscore the potential of gut microbiota analysis in non-invasively monitoring CKD, especially in older populations, and hint at future interventions targeting gut microbiota to manage CKD progression. Further research is needed for causal relationships and generalizability.

Background: Disruptions in gut microbiota compositiosn (dysbiosis) in kidney diseases can lead to worsened kidney function. Dysbiosis may increase intestinal permeability and systemic inflammation, allowing bacterial toxins to enter the bloodstream and exacerbate CKD and its complications. This systematic review aims to evaluate the association of intestinal microbiota and kidney disease by analyzing available studies of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Gut microbiota alterations are closely linked to chronic kidney disease (CKD) and end-stage renal disease (ESRD), impacting inflammation and disease progression. Microbial shifts offer potential diagnostic and therapeutic insights, though further research is needed for clinical application.

Background: Disruptions in gut microbiota compositiosn (dysbiosis) in kidney diseases can lead to worsened kidney function. Dysbiosis may increase intestinal permeability and systemic inflammation, allowing bacterial toxins to enter the bloodstream and exacerbate CKD and its complications. This systematic review aims to evaluate the association of intestinal microbiota and kidney disease by analyzing available studies of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Gut microbiota alterations are closely linked to chronic kidney disease (CKD) and end-stage renal disease (ESRD), impacting inflammation and disease progression. Microbial shifts offer potential diagnostic and therapeutic insights, though further research is needed for clinical application.

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.

Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota-driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro-inflammatory and immunomodulatory responses depending on their chemical structures. Herein we report the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol-containing O-antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid-phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whereas pro-inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible "immune modulating" action has been proposed for the peculiar O-antigen portion.

Producción Científica, Circadian rhythms integrate a finely tuned network of biological processes recurring every 24 h, intricately coordinating the machinery of all cells. This self-regulating system plays a pivotal role in synchronizing physiological and behavioral responses, ensuring an adaptive metabolism within the environmental milieu, including dietary and physical activity habits. The systemic integration of circadian homeostasis involves a balance of biological rhythms, each synchronically linked to the central circadian clock. Central to this orchestration is the temporal dimension of nutrient and food intake, an aspect closely interwoven with the neuroendocrine circuit, gut physiology, and resident microbiota. Indeed, the timing of meals exerts a profound influence on cell cycle regulation through genomic and epigenetic processes, particularly those involving gene expression, DNA methylation and repair, and non-coding RNA activity. These (epi)genomic interactions involve a dynamic interface between circadian rhythms, nutrition, and the gut microbiota, shaping the metabolic and immune landscape of the host. This research endeavors to illustrate the intricate (epi)genetic interplay that modulates the synchronization of circadian rhythms, nutritional signaling, and the gut microbiota, unravelling the repercussions on metabolic health while suggesting the potential benefits of feed circadian realignment as a non-invasive therapeutic strategy for systemic metabolic modulation via gut microbiota. This exploration delves into the interconnections that underscore the significance of temporal eating patterns, offering insights regarding circadian rhythms, gut microbiota, and chrono-nutrition interactions with (epi)genomic phenomena, thereby influencing diverse aspects of metabolic, well-being, and quality of life outcomes., Instituto Carlos III, Contratos Sara Borrell - (grant CD22/00011), Comunidad Autónoma de Madrid, Consejería de Educación, CIBERobn, Instituto IMDEA Alimentación - (project METAINFLAMACION: Y2020/BIO-6600)

Background Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women aficted with CHD and delineate these against a non-CVD control group for each sex. Methods Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our fndings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software. Results Our results showed a sex-specifc variation (beta diversity) in the intestinal microbiota, while alpha-biodiver‑ sity remained consistent across both sexes. Linear discriminant analysis efect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identifed seven bacterial taxa—g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)—as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-aficted and non-CVD individuals, when analyzed separately by sex. Conclusion Our fndings suggest a sex-specifc dysbiosis in the intestinal microbiota linked to CHD, potentially con‑ tributing to the sex disparity observed in CVD incidence.

The potential health impact of exposure to anthropogenic chemicals has raised major concerns worldwide. Phthalates are mainly used in the plastic industry and have been associated with adverse effects in humans. Di-n-butyl phthalate (DBP) is one of the dominant phthalates with a ubiquitous presence in the environment. While many studies have examined the endocrine disrupting properties of DBP, with a focus on developmental and reproductive dysfunctions, studies of its effects on the adult reproductive system and gut microbiota are limited. This thesis aimed to determine persistent effects of DBP on the adult male reproductive system, provide a high-throughput screening tool for identifying reproductive toxicants, and characterize the effects of DBP on the gut microbiota. Paper I investigated if adult DBP exposure can induce persistent effects on the mature reproductive system. Adult male mice were orally exposed to 10 or 100 mg/kg/day for five weeks and testes were collected one week after the last dose. The results demonstrated a significant decrease in testosterone levels in the DBP-exposed groups. Mechanistically, the levels of steroidogenic enzymes, cell-specific markers and oxidative stress were increased. In paper II, elements of the in vivo testicular microenvironment, including functional testosterone production, were modeled using a three-dimensional (3D) heterogenous testicular cell co-culture derived from neonatal mice. Automated high-content imaging of cell-specific markers confirmed the presence of germ cells (DAZL+), Leydig cells (CYP11A1+), and Sertoli cells (SOX9+). DBP exposure decreased testosterone production, as well as levels of the steroidogenic enzyme CYP11A1, and the steroidogenic regulator StAR. Overall, this in vitro 3D model recapitulates the testicular pathways involved in DBP toxicity, making it a relevant tool for assessing reprotoxic effects of chemicals. Paper III investigated the impact of oral DBP exposure on the gut microbiot

The potential health impact of exposure to anthropogenic chemicals has raised major concerns worldwide. Phthalates are mainly used in the plastic industry and have been associated with adverse effects in humans. Di-n-butyl phthalate (DBP) is one of the dominant phthalates with a ubiquitous presence in the environment. While many studies have examined the endocrine disrupting properties of DBP, with a focus on developmental and reproductive dysfunctions, studies of its effects on the adult reproductive system and gut microbiota are limited. This thesis aimed to determine persistent effects of DBP on the adult male reproductive system, provide a high-throughput screening tool for identifying reproductive toxicants, and characterize the effects of DBP on the gut microbiota. Paper I investigated if adult DBP exposure can induce persistent effects on the mature reproductive system. Adult male mice were orally exposed to 10 or 100 mg/kg/day for five weeks and testes were collected one week after the last dose. The results demonstrated a significant decrease in testosterone levels in the DBP-exposed groups. Mechanistically, the levels of steroidogenic enzymes, cell-specific markers and oxidative stress were increased. In paper II, elements of the in vivo testicular microenvironment, including functional testosterone production, were modeled using a three-dimensional (3D) heterogenous testicular cell co-culture derived from neonatal mice. Automated high-content imaging of cell-specific markers confirmed the presence of germ cells (DAZL+), Leydig cells (CYP11A1+), and Sertoli cells (SOX9+). DBP exposure decreased testosterone production, as well as levels of the steroidogenic enzyme CYP11A1, and the steroidogenic regulator StAR. Overall, this in vitro 3D model recapitulates the testicular pathways involved in DBP toxicity, making it a relevant tool for assessing reprotoxic effects of chemicals. Paper III investigated the impact of oral DBP exposure on the gut microbiot

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis (GBA) in the context of AD progression and pathology have yielded inconsistent findings. This review aims to enhance our understanding of microbial diversity at the species level and the role of these species in AD pathology. Additionally, this review addresses the influence of confounding elements, including diet, probiotics, and prebiotics, on AD throughout different stages (preclinical, mild cognitive impairment (MCI), and AD) of its progression.

The supplementation of antimicrobial growth promoters (AGPs) has been banned in many countries because of the emergence of antimicrobial-resistant pathogens in poultry products and the environment. Probiotics have been broadly studied and demonstrated as a promising AGP substitute. Our study is centred on the effects of a multi-strain Bacillus-based probiotic product on broiler production performance and gut microbial profile in a dexamethasone-induced leaky gut challenge. Two hundred and fifty-six broiler chicks were hatched and randomly assigned into four groups (wheat-soybean meal basal diet (BD) = non-supplemented control (C), BD supplemented with dexamethasone in week 4 (CD), BD containing a probiotic from day one (P), and BD containing a probiotic from day one and supplemented with dexamethasone during challenge week 4 (PD)). The production performance and caecal, gizzard, jejunal lumen and jejunal mucosa swab microbiota were studied by 16S rRNA gene sequencing. The Bacillus probiotic product significantly improved production performance and altered caecal gut microbiota (p ≤ 0.05), but no significant impact on microbiota was observed in other gut sections.

Normally, the bacteria residing in our gut, the so-called gut microbiota, live in a balance and closely interact with the human body. However, this balance can be disturbed, for instance by the development and subsequent treatment of human cancer. This dissertation investigated the effects of chemotherapy and cancer cachexia (a syndrome which is characterized by severe muscle loss) on the gut microbiota. Furthermore, it evaluated whether prebiotics could be used to counteract these effects by stimulating gut bacteria with beneficial properties. While the gut microbiota currently receives little attention during anti-cancer treatment, the insights gained in the context of this thesis could contribute to establishing gut microbiota-modulating interventions in cancer patients in the future.

This research investigates the effects of phytogenic feed additives (PFAs) on the growth performance, gut microbial community, and microbial metabolic functions in weaned piglets via a combined 16S rRNA gene amplicon and shotgun metagenomics approach. A controlled trial was conducted using 200 pigs to highlight the significant influence of PFAs on gut microbiota dynamics. Notably, the treatment group revealed an increased gut microbiota diversity, as measured with the Shannon and Simpson indices. The increase in diversity is accompanied by an increase in beneficial bacterial taxa, such as Roseburia, Faecalibacterium, and Prevotella, and a decline in potential pathogens like Clostridium sensu stricto 1 and Campylobacter. Shotgun sequencing at the species level confirmed these findings. This modification in microbial profile was coupled with an altered profile of microbial metabolic pathways, suggesting a reconfiguration of microbial function under PFA influence. Significant shifts in overall microbial community structure by week 8 demonstrate PFA treatment’s temporal impact. Histomorphological examination unveiled improved gut structure in PFA-treated piglets. The results of this study indicate that the use of PFAs as dietary supplements can be an effective strategy, augmenting gut microbiota diversity, reshaping microbial function, enhancing gut structure, and optimising intestinal health of weaned piglets providing valuable implications for swine production. Key points • PFAs significantly diversify the gut microbiota in weaned piglets, aiding balance. • Changes in gut structure due to PFAs indicate improved resistance to weaning stress. • PFAs show potential to ease weaning stress, offering a substitute for antibiotics in piglet diets.

Background Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women aficted with CHD and delineate these against a non-CVD control group for each sex. Methods Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our fndings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software. Results Our results showed a sex-specifc variation (beta diversity) in the intestinal microbiota, while alpha-biodiver‑ sity remained consistent across both sexes. Linear discriminant analysis efect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identifed seven bacterial taxa—g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)—as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-aficted and non-CVD individuals, when analyzed separately by sex. Conclusion Our fndings suggest a sex-specifc dysbiosis in the intestinal microbiota linked to CHD, potentially con‑ tributing to the sex disparity observed in CVD incidence.

Particle size is one of the most important factors in determining the biological toxicity of microplastics (MPs). In this study, we attempted to examine the systemic toxicity of polystyrene MPs of different sizes (0.5 µm MP1 and 5 µm MP2) in C57BL/6 J mice. After the mice were given oral gavage of MPs for 8 consecutive weeks, histopathology and molecular biology assays, 16 S rRNA sequencing of the gut microbiota, and untargeted metabolomics were performed. The results showed that MPs were distributed in the organs in a size-dependent manner, with smaller particles demonstrating greater biodistribution. Further analysis indicated that exposure to MPs caused multi-organ damage through distinct toxicity pathways. Specifically, exposure to 0.5 µm MP1 led to excessive accumulation and induced more serious inflammation and mechanical damage in the spleen, kidney, heart, lung, and liver. However, 5 µm MP2 led to more severe intestinal barrier dysfunction, as well as gut dysbiosis and metabolic disorder in association with neuroinflammation. These results are helpful in expanding our knowledge of the toxicity of MPs of different sizes in mammalian models. © 2023 Elsevier B.V.

Randomly barcoded transposon mutant libraries are powerful tools for studying gene function and organization, assessing gene essentiality and pathways, discovering potential therapeutic targets, and understanding the physiology of gut bacteria and their interactions with the host. However, construction of high-quality libraries with uniform representation can be challenging. In this review, we survey various strategies for barcoded library construction, including transposition systems, methods of transposon delivery, optimal library size, and transconjugant selection schemes. We discuss the advantages and limitations of each approach, as well as factors to consider when selecting a strategy. In addition, we highlight experimental and computational advances in arraying condensed libraries from mutant pools. We focus on examples of successful library construction in gut bacteria and their application to gene function studies and drug discovery. Given the need for understanding gene function and organization in gut bacteria, we provide a comprehensive guide for researchers to construct randomly barcoded transposon mutant libraries.

There is evidence of the influence of the intestinal microbiota on the response to immunotherapy in cancer. In addition, we lack markers of response to treatment and toxicity, which obliges us to continue our search for them. In this work, we recruited patients with non-small-cell lung cancer receiving immunotherapy who contributed a fecal and blood sample. We analyzed the possible relationship between the response to immune checkpoint inhibitors and the occurrence of immune-related adverse events, the composition (16S rDNA amplification) and functionality (abundance of short-chain fatty acids) of the gut microbiota, and intestinal membrane permeability as a human factor. No correlations were detected between analytical markers and clinical evolution, with a marked individuality of the gut microbiota in terms of composition, but homogeneity in its functionality and permeability. Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host–microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients’ microbial

The synergies between selective breeding and feed additives remain under-explored in farmed fish, despite their sustainability. Reference (REF) and selected gilthead sea bream for growth (GS) were fed with the control (CTRL) diet during 14 days. CTRL diet was oil-coated with three functional additives (PHY: phytogenic based on garlic and medium chain fatty acid; OA: organic acid mixture with a 70% of butyric acid sodium salt; PROB: probiotic based on Bacillus subtilis, pumillus and licheniformes species). These experimental diets were then sequentially administered at high (PHY/OA = 7.5 g/kg, PROB = 2 × 1011 CFU/kg; 2 weeks) and low (PHY = 5 g/kg, OA = 3 g/kg, PROB = 4 × 1010 CFU/kg; 10 weeks) additive doses. The capacity of a given genotype and additive to modify the fish growth performance, gut health and the host interaction with its anterior intestine (AI) microbiota was evaluated as a whole population or individually (9 fish/diet/genetics). GS fish showed a better growth and feed conversion ratio, linked to a reduced individual variability of gut microbial composition. The PHY additive had a major impact upon the intestinal transcriptome of GS-PHY fish, with the up-regulation of markers of epithelial integrity, sphingolipid and cholesterol/bile salt metabolism. With the OA additive, impaired growth performance, reduced AI goblet cell area and enhanced AI granulocyte infiltration were concomitant with a down-regulation of neutrophil degranulation markers associated with a decrease of pathogenic genera (Staphylococcus/Streptococcus/Neisseria), and an over-representation of acetone/butanol/ethanol fermentation and vitamin K biosynthesis inferred pathways. Bacillus establishment and lack of AI inflammation were parallel in PROB fish of both genetic backgrounds. However, GS fish grew and utilized feed better with the additive, whereas a worsening appeared in REF fish. This amelioration was related with a higher abundance of the nitrate-reducer Kocuria, an up-regulat

The objective of this study was to test the effects of CGN consumption on the gut microbiota and the intestinal homeostasis of male and female young mice. Female and male ICR-CD1 mice (8 weeks old) received orally 540 mg/kg/day of CGN. Fecal material was analyzed to describe changes in the fecal microbiota, based on the analysis of bacterial 16S rRNA gene (V3-V4 region) amplicon sequences. Non-significant microbiota taxonomical changes associated to CGN intake were obtained in the mice stools, resulting the housing time in an increase of bacterial groups belonging to the Bacteroidota phylum. The PICRUSt2 functional predictions based on 16S rDNA amplicons showed an overall increase in functional clusters of orthologous genes (COG) involved in carbohydrate transport and metabolism. A significant increase in citotoxicity of fecal supernatants was observed in CGN-fed mice.

Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro-inflammatory and immunomodulatory responses depending on their chemical structures. Here we report about the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol-containing O-antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whether a pro-inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible “immune modulating” action has been proposed for the peculiar O-antigen portion.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that displays great variability in clinical phenotype. Many factors have been described to be correlated with its severity but no specific determinants of infection outcome have been identified yet, maybe due the complex pathogenic mechanisms. The microbiota could play a key role in the infection and in the progression and outcome of the disease. Hence, SARS-CoV-2 infection has been associated with nasopharyngeal and gut dysbiosis and higher abundance of opportunistic pathogens. Methods: To identify new prognostic markers for the disease, a multicenter prospective observational cohort study was carried out in COVID-19 patients that were divided in three cohorts according to their symptomatology: mild (n=24), moderate (n=51) and severe/critical (n=31). Faecal and nasopharyngeal samples were taken and the microbiota was analysed. Results: Microbiota composition could be associated with the severity of the symptoms and the linear discriminant analysis identified the genera Mycoplasma and Prevotella as severity biomarkers in nasopharyngeal samples, and Allistipes, Enterococcus and Escherichia in faecal samples. Moreover, M. salivarium was defined as a unique microorganism in COVID-19 patients' nasopharyngeal microbiota while P. bivia and P. timonensis were defined in faecal microbiota. A connection between faecal and nasopharyngeal microbiota in COVID-19 patients was also identified as a strong positive correlation between P. timonensis (faeces) towards P. dentalis and M. salivarium(nasopharyngeal) was found in critically ill patients. Conclusions: This ratio could be used as a novel prognostic biomarker for severe COVID-19 patients.

Increasing evidence of sexual dimorphism in the pathophysiology of metabolic complications caused by sex steroids is under investigation. The gut microbiota represents a complex microbial ecosystem involved in energy metabolism, immune response, nutrition acquisition, and the health of host organisms. Gender-specific differences in composition are present between females and males. The purpose of this study was to use cross-sex fecal microbiota transplantation (FMT) for the detection of sex-dependent metabolic, hormonal, and gut microbiota changes in female and male recipients. Healthy non-obese female and male Wistar rats were divided into donor, same-sex, and cross-sex recipient groups. After a 30-day period of FMT administration, biochemical markers (glucose and lipid metabolism) and sex hormones were measured, and the gut microbiota was analyzed. The cross-sex male recipients displayed a significantly lower testosterone concentration compared to the males that received same-sex FMT. Sex-dependent changes caused by cross-sex FMT were detected, while several bacterial taxa correlated with plasma testosterone levels. This study represents the first to study the effect of cross-sex changes in the gut microbiome concerning metabolic and hormonal changes/status in adult non-obese Wistar rats. Herein, we present cross-sex FMT as a potential tool to modify sex-specific pathologies.

Background: The metabolic disturbances of obesity can be mitigated by strategies modulating the gut microbiota. In this study, we sought to identify whether innate or adaptive immunity mediates the beneficial metabolic effects of the human intestinal bacterium Bacteroides uniformis CECT 7771 in obesity. Methods: We evaluated the effects of orally administered B. uniformis on energy homeostasis, intestinal immunity, hormone levels, and gut microbiota in wild-type and Rag1-deficient mice with diet-induced obesity. We also assessed whether B. uniformis needed to be viable to exert its beneficial effects in obesity and to directly induce immunoregulatory effects. Results: The administration of B. uniformis to obese mice improved glucose tolerance and insulin secretion, restored the caloric intake suppression after an oral glucose challenge, and reduced hyperglycemia. The pre- and post-prandial glucose-related benefits were associated with restoration of the anti-inflammatory tone mediated by type 2 macrophages and regulatory T cells (Tregs) in the lamina propria of the small intestine. Contrastingly, B. uniformis administration failed to improve glucose tolerance in obese Rag1-/- mice, but prevented the increased body weight gain and adiposity. Overall, the beneficial effects seemed to be independent of enteroendocrine effects and of major changes in gut microbiota composition. B. uniformis directly induced Tregs generation from naïve CD4+ T cells in vitro and was not required to be viable to improve glucose homeostasis but its viability was necessary to prevent body weight gain in diet-induced obese wild-type mice. Conclusions: Here we demonstrate that B. uniformis modulates the energy homeostasis in diet-induced obese mice through different mechanisms. The bacterium improves oral glucose tolerance by adaptive immunity-dependent mechanisms that do not require cell viability and prevents body weight gain by adaptive immunity-independent mechanisms which require cell via

Background: Animal and human studies indicate that exposure to air pollution and natural environments might modulate the gut microbiota, but epidemiological evidence is very scarce. Objectives: To assess the potential impact of pre- and postnatal exposure to air pollution and green spaces on infant gut microbiota assembly and trajectories during the first year of life. Methods: MAMI (“MAternal MIcrobes”) birth cohort (Valencia, Spain, N = 162) was used to study the impact of environmental exposure (acute and chronic) on infant gut microbiota during the first year of life (amplicon-based 16S rRNA sequencing). At 7 days and at 1, 6 and 12 months, residential pre- and postnatal exposure to air pollutants (NO2, black carbon -BC-, PM2.5 and O3) and green spaces indicators (NDVI and area of green spaces at 300, 500 and 1000 m buffers) were obtained. For the association between exposures and alpha diversity indicators linear regression models (cross-sectional analyses) and mixed models, including individual as a random effect (longitudinal analyses), were applied. For the differential taxon analysis, the ANCOM-BC package with a log count transformation and multiple-testing corrections were used. Results: Acute exposure in the first week of life and chronic postnatal exposure to NO2 were associated with a reduction in microbial alpha diversity, while the effects of green space exposure were not evident. Acute and chronic (prenatal or postnatal) exposure to NO2 resulted in increased abundance of Haemophilus, Akkermansia, Alistipes, Eggerthella, and Tyzerella populations, while increasing green space exposure associated with increased Negativicoccus, Senegalimassilia and Anaerococcus and decreased Tyzzerella and Lachnoclostridium populations. Discussion: We observed a decrease in the diversity of the gut microbiota and signs of alteration in its composition among infants exposed to higher levels of NO2. Increasing green space exposure was also associated with changes in gut m

Growing evidence indicates that gut and respiratory microbiota have a potential key effect on bronchiolitis, mainly caused by respiratory syncytial virus (RSV). This was a prospective study of 96 infants comparing infants with bronchiolitis (n = 57, both RSV and non-RSV associated) to a control group (n = 39). Gut (feces) and respiratory [nasopharyngeal aspirate (NPA)] microbial profiles were analyzed by 16S rRNA amplicon sequencing, and respiratory viruses were identified by PCR. Clinical data of the acute episode and follow-up during the first year after infection were recorded. Pairwise comparisons showed significant differences in the gut (R2 = 0.0639, P = 0.006) and NPA (R2 = 0.0803, P = 0.006) microbiota between cases and controls. A significantly lower gut microbial richness and an increase in the NPA microbial diversity (mainly due to an increase in Haemophilus, Streptococcus, and Neisseria) were observed in the infants with bronchiolitis, in those with the most severe symptoms, and in those who subsequently developed recurrent wheezing episodes after discharge. In NPA, the higher microbial richness differed significantly between the control group and the non-RSV bronchiolitis group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001). In the gut, the richness differed significantly between the control group and the non-RSV group (P = 0.01) and between the control group and the RSV bronchiolitis group (P = 0.001), with higher diversity in the RSV group. A distinct respiratory and intestinal microbial pattern was observed in infants with bronchiolitis compared with controls. The presence of RSV was a main factor for dysbiosis. Lower gut microbial richness and increased respiratory microbial diversity were associated with respiratory morbidity during follow-up.

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind t

The imbalance of the gut microbiota (GM) is known as dysbiosis and is associated with disorders such as obesity. The increasing prevalence of microorganisms harboring antibiotic resistance genes (ARG) in the GM has been reported as a potential risk for spreading multi-drug-resistant pathogens. The objective of this work was the evaluation, in a fecal culture model, of different probiotics for their ability to modulate GM composition and ARG levels on two population groups, extremely obese (OB) and normal-weight (NW) subjects. Clear differences in the basal microbiota composition were observed between NW and OB donors. The microbial profile assessed by metataxonomics revealed the broader impact of probiotics on the OB microbiota composition. Also, supplementation with probiotics promoted significant reductions in the absolute levels of tetM and tetO genes. Regarding the blaTEM gene, a minor but significant decrease in both donor groups was detected after probiotic addition. A negative association between the abundance of Bifidobacteriaceae and the tetM gene was observed. Our results show the ability of some of the tested strains to modulate GM. Moreover, the results suggest the potential application of probiotics for reducing the levels of ARG, which constitutes an interesting target for the future development of probiotics.

The aim of this study was to investigate the effects of enzymatic treatments (pectinase, pectin lyase, and cellulase) on the in vitro digestion and fermentation characteristics of whole mulberry fruit juice. The analysis focused on changes in carbohydrate properties within the black mulberry fruit matrix during simulated digestion and fermentation. Human fecal microbiota were collected and introduced to the fruit matrix to monitor the fate of both soluble and insoluble polysaccharides during fermentation. The results revealed that enzymatic treatments enhanced the solubilization of carbohydrates from mulberry fruits, with pectinase showing the most significant effect. Throughout the process of in vitro digestion, there was a gradual increase in the percentage of solubilized carbohydrates from the mulberry juice substrate. The digested suspensions underwent dialysis to remove degradation fragments, and a lower quantity of carbohydrate in the enzyme-treated groups compared to the control. Polysaccharide populations with varying molecular weights (Mw) were obtained from the soluble fractions of mulberry residues for subsequent fermentation. An increase in Mw of soluble polysaccharides was detected by HPSEC during fermentation in certain cases. The gut microbiota demonstrated the ability to convert specific insoluble fractions into soluble components, which were subsequently subjected to microbial utilization. Enzymatic treatments during mulberry juice preparation can potentially positively impact health by influencing gut microbiota and short-chain fatty acid (SCFA) modulations. Enzymes could serve as valuable tools for producing functional fruit and vegetable juices, with the need to specify processing conditions for specific raw materials remaining a subject of further investigation.

Observational studies have determined numerous correlations between sequence-based gut microbiota data and human mental traits. However, these associations are often inconsistent across studies. This inconsistency is one of the reasons that mechanistic validation studies of the observed correlations are lagging, making it difficult to establish causal associations. The absence of consistent study findings may partially be due to the lack of clear guidelines for identifying confounders of relations between complex microbial communities and mental conditions. Gut microbial complexity also impedes deciphering microbiota-host relations by using a single analytical approach. The aim of the current review is to help solve these problems by providing methodological recommendations for future human microbiota-gut-brain axis research on the selection of confounders, the use of integrative biostatistical methods, and the steps needed to translate correlative findings into causal conclusions.

This study explored differences in microbial lipid metabolites among sunflower seeds, soybeans, and walnuts. The matrices were subjected to in vitro digestion and colonic fermentation. Defatted digested materials and fiber/phenolics extracted therefrom were added to sunflower oil (SO) and also fermented. Targeted and untargeted lipidomics were employed to monitor and tentatively identify linoleic acid (LA) metabolites. Walnut fermentation produced the highest free fatty acids (FFAs), LA, and conjugated LAs (CLAs). Defatted digested walnuts added to SO boosted FFAs and CLAs production; the addition of fibre boosted CLAs, whereas the addition of phenolics only increased 9e,11z-CLA and 10e,12z-CLA. Several di-/tri-hydroxy-C18-FAs, reported as microbial LA metabolites for the first time, were annotated. Permutational multivariate analysis of variance indicated significant impacts of food matrix presence and type on lipidomics and C18-FAs. Our findings highlight how the food matrices affect CLA production from dietary lipids, emphasizing the role of food context in microbial lipid metabolism.

Aims/hypothesis: We aimed to investigate the association between the abundance of Dysosmobacter welbionis, a commensal gut bacterium, and metabolic health in human participants with obesity and diabetes, and the influence of metformin treatment and prebiotic intervention. Methods: Metabolic variables were assessed and faecal samples were collected from 106 participants in a randomised controlled intervention with a prebiotic stratified by metformin treatment (Food4Gut trial). The abundance of D. welbionis was measured by quantitative PCR and correlated with metabolic markers. The in vitro effect of metformin on D. welbionis growth was evaluated and an in vivo study was performed in mice to investigate the effects of metformin and D. welbionis J115T supplementation, either alone or in combination, on metabolic variables. Results: D. welbionis abundance was unaffected by prebiotic treatment but was significantly higher in metformin-treated participants. Responders to prebiotic treatment had higher baseline D. welbionis levels than non-responders. D. welbionis was negatively correlated with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and fasting blood glucose levels in humans with obesity and type 2 diabetes. In vitro, metformin had no direct effect on D. welbionis growth. In mice, D. welbionis J115T treatment reduced body weight gain and liver weight, and improved glucose tolerance to a better level than metformin, but did not have synergistic effects with metformin. Conclusions/interpretation: D. welbionis abundance is influenced by metformin treatment and associated with prebiotic response, liver health and glucose metabolism in humans with obesity and diabetes. This study suggests that D. welbionis may play a role in metabolic health and warrants further investigation. Clinical trial: NCT03852069 Graphical Abstract: [Figure not available: see fulltext.]., SCOPUS: ar.j, info:eu-repo/semantics/published

In this thesis, we delved deep into the connection between gut microbes, their metabolic byproducts, and two major health concerns: hypertension and Alzheimer’s disease. The first part delves into the associations between gut microbiota, metabolites and blood pressure. Our research revealed a complex relationship between gut bacteria, particularly those involved in producing short-chain fatty acids (SCFAs), and blood pressure regulation using data of the population-based HELIUS cohort. While some bacteria seemed to have a positive effect on lowering blood pressure, we were surprised to find that oral butyrate, a type of SCFA, actually increased blood pressure in our clinical trial. Our metabolomics analyses in the HELIUS cohort revealed intriguing insights into the associations between plasma metabolites and blood pressure regulation. Formylmethionine emerged as a novel metabolite strongly linked to higher blood pressure, potentially indicating a role in blood pressure regulation. Furthermore, sex-specific analyses uncovered distinct plasma metabolite patterns associated with blood pressure, highlighting potential differences in hypertension physiology between men and women. These findings offer valuable leads for further mechanistic studies on the role of metabolites in hypertension. In the second part of this thesis, we investigated the associations of nutritional status and gut microbiota composition with Alzheimer's disease biomarkers. We found that lower indicators of nutritional status were associated with more atrophy on MRI, specifically global cortical atrophy and medial temporal atrophy. The findings highlight the importance of maintaining good nutritional status in patients with Alzheimer’s disease. In our analyses on gut microbiota composition and Alzheimer's disease pathology, we found that the abudance of specific gut microbes are associated with Alzheimer's disease biomarkers. In conclusion, the studies of this second part of this thesis shed light on

Probiotics and postbiotics mechanisms of action and applications in early-onset colorectal cancer (EOCRC) prevention and treatment have significant importance but are a matter of debate and controversy. Therefore, in this review, we aimed to define the probiotics concept, advantages and limitations in comparison to postbiotics, and proposed mechanisms of anti-tumor action in EOCRC prevention and treatment of postbiotics. Biotics (probiotics, prebiotics, and postbiotics) could confer the health benefit by affecting the host gut microbiota directly and indirectly. The main mechanisms of action of probiotics in exerting anticancer features include immune system regulation, inhibition of cancer cell propagation, gut dysbiosis restoration, anticancer agents’ production, gut barrier function renovation, and cancer-promoting agents’ reduction. Postbiotics are suggested to have different mechanisms of action to restore eubiosis against EOCRC, including modulation of gut microbiota composition, gut microbial metabolites regulation, and intestinal barrier function improvement via different features such as immunomodulatory, anti-inflammatory, antioxidant, and anti-proliferative properties. A better understanding of postbiotics challenges and mechanism of action in therapeutic applications will allow us to sketch accurate trials in order to use postbiotics as bio-therapeutics in EOCRC., Probiotics and postbiotics mechanisms of action and applications in early-onset colorectal cancer (EOCRC) prevention and treatment have significant importance but are a matter of debate and controversy. Therefore, in this review, we aimed to define the probiotics concept, advantages and limitations in comparison to postbiotics, and proposed mechanisms of anti-tumor action in EOCRC prevention and treatment of postbiotics. Biotics (probiotics, prebiotics, and postbiotics) could confer the health benefit by affecting the host gut microbiota directly and indirectly. The main mechanisms of action of probiotics in exerting anticancer features include immune system regulation, inhibition of cancer cell propagation, gut dysbiosis restoration, anticancer agents’ production, gut barrier function renovation, and cancer-promoting agents’ reduction. Postbiotics are suggested to have different mechanisms of action to restore eubiosis against EOCRC, including modulation of gut microbiota composition, gut microbial metabolites regulation, and intestinal barrier function improvement via different features such as immunomodulatory, anti-inflammatory, antioxidant, and anti-proliferative properties. A better understanding of postbiotics challenges and mechanism of action in therapeutic applications will allow us to sketch accurate trials in order to use postbiotics as bio-therapeutics in EOCRC.