Altered Microbiota Composition Research Articles

Pediatric kidney transplant recipients are at an increased risk for dysbiosis

IntroductionThis study aimed to compare the gut microbiota composition in pediatric kidney transplant (KTx) recipient with that of healthy children.MethodsThis cross-sectional observational study included 30 pediatric KTx recipients aged between 7 and 21 years and 25 healthy children. The gut microbiota was assessed using 16S rRNA gene sequencing, with alpha and beta diversity, as well as all statistical analyses, conducted using the Phyloseq library in the R programming language. Taxonomic profiles were evaluated with QIIME2, and differences in gut microbiota profiles were compared using linear discriminant analysis effect size (LEFSe) with an LDA threshold of >2 and p < 0.05.ResultsNo significant differences were found in alpha and beta diversity between the KTx recipients and healthy controls. However, KTx recipients exhibited significant alterations in microbiota composition, including higher relative abundances of Verrucomicrobiota at the phylum level, and Akkermansia and Neisseria at the genus level (p < 0.05 for all). Conversely, there was a decrease in bacterial genera belonging to the phylum Firmicutes. In addition, KTx recipients with a history of frequent urinary tract infections, diarrhea and reduced GFR showed significant increases in bacterial abundance (p < 0.05 for all).DiscussionPediatric KTx recipients demonstrated significant alterarions in gut microbiota composition, indicating dysbiosis. Further studies are needed to elucidate the cause-and-effect relationships of these changes and their impact on clinical consequencies and long-term prognosis.

Daily feeding frequency impacts muscle characteristics and fat deposition in finishing pigs associated with alterations in microbiota composition and bile acid profile

IntroductionFeeding frequency has been shown to affect growth and body composition of the host associated with gut microbiota. It remains unknown whether adjusting feeding frequency could effectively regulate both skeletal muscle development and whole-body lipid metabolism and thus affect carcass composition and feed conversion efficiency. Therefore, this study aimed to explore the effects of feeding frequency on muscle growth, fat deposition, cecal microbiota composition, and bile acid composition in finishing pigs.MethodsSixteen Sichuan-Tibetan black pigs, with an initial weight of 121.50 ± 1.60 kg, were divided into two groups and fed either two meals (M2) or four meals (M4) per day. The trial lasted 30 days. The muscle fiber characteristics, lipid metabolism in adipose tissue, and cecal microbiota and bile acid composition were determined.ResultsThe present study revealed that pigs fed four meals exhibited a lower feed-to-gain ratio, abdominal fat weight, and average backfat thickness (p < 0.05), as well as a higher loin eye area (p = 0.09) and myofiber diameter in the longissimus muscle than their counterparts. The mRNA expression of slow-twitch fiber and myogenesis-associated genes in the longissimus muscle was upregulated, while lipid metabolism-related genes in the backfat were downregulated in the M4 group compared to the M2 group (p < 0.05). The M4 pigs exhibited higher abundances of Firmicutes, Actinobacteriota, Bacillus, Clostridium_sensu_1, and Romboutsia, and lower abundances of Spirochaetota, Verrucomicrobiota, Treponema, and Muribaculaceae in the cecal content than the M2 pigs (p < 0.05). A higher feeding frequency increased the levels of primary bile acids and decreased the concentrations of taurine-conjugated bile acids in the cecal content of pigs (p < 0.05).ConclusionOur research suggested that the M4 feeding pattern, compared to the M2 pattern, promoted muscle growth and reduced fat deposition by enhancing fast- to slow-twitch fiber conversion and myogenesis in the muscle and repressing lipid metabolism in adipose tissue, associated with altered microbiota composition and bile acid profiles.

Mucus-penetrating microbiota drive chronic low-grade intestinal inflammation and metabolic dysregulation

ABSTRACT Metabolic syndrome is, in humans, associated with alterations in the composition and localization of the intestinal microbiota, including encroachment of bacteria within the colon’s inner mucus layer. Possible promoters of these events include dietary emulsifiers, such as carboxymethylcellulose (CMC) and polysorbate-80 (P80), which, in mice, result in altered microbiota composition, encroachment, low-grade inflammation and metabolic syndrome. While assessments of gut microbiota composition have largely focused on fecal/luminal samples, we hypothesize an outsized role for changes in mucus microbiota in driving low-grade inflammation and its consequences. In support of this notion, we herein report that both CMC and P80 led to stark changes in the mucus microbiome, markedly distinct from those observed in feces. Moreover, transfer of mucus microbiota from CMC- and P80-fed mice to germfree mice resulted in microbiota encroachment, low-grade inflammation, and various features of metabolic syndrome. Thus, we conclude that mucus-associated bacteria are pivotal determinants of intestinal inflammatory tone and host metabolism.

The Impact of Hangeshashinto on Symptoms and Gut Microbiota in Diarrhea-type Irritable Bowel Syndrome: A Retrospective Analysis

Effective treatments for diarrhea-type irritable bowel syndrome (IBS-D) are limited. Hangeshashinto (HST), an anti-inflammatory Kampo medicine, may offer benefits but its efficacy for IBS-D requires further investigation. This study evaluated IBS-D symptom improvement and gut microbiota changes following HST administration. This was a multicenter retrospective study with a prospective analysis of microbiota conducted at five affiliated institutions. Patients diagnosed with IBS-D based on the ROME IV criteria between April 2019 and December 2023, who received HST 7.5 g/day for 2-3 weeks were included. The outcome measures were improvement rates in overall symptoms, stool frequency, stool consistency, and abdominal pain. Intestinal microbiota was analyzed using 16S rRNA gene sequencing from fecal samples of 20 patients before and after HST treatment. One hundred patients (42 males/58 females, mean age: 69.5±11.8 years) were analyzed. The overall improvement rate of HST was 82.0%. Those of males and females were 81.0% and 82.8% (p=0.816). By age, those of patients aged ≥75 and aged <75 years were 82.9% and 81.5% (p=0.869). The improvement rates of stool frequency, stool consistency, and abdominal pain were 59.0%, 51.0%, and 62.0%, respectively. The stool frequency per week before and after HST was 21.7±18.2 vs. 14.0±12.6 (p<0.001). Significant differences in gut microbiota β diversity were observed, although α diversity was not significantly changed. Bacteroides (p=0.003) and Ruminococcus (p=0.010) decreased significantly, while Megasphaera (p=0.030) and Subdoligranulum (p=0.002) increased. HST may improve IBS-D symptoms by altering microbiota composition.

Identifying fecal microbiota signatures of colorectal cancer in a Vietnamese cohort.

Colorectal cancer (CRC) is among the top three causes of global cancer mortality. In Vietnam, CRC is the third leading cause of death in women and the fourth cause of cancer mortality in men. A large number of metagenomic studies have reported the relationship between altered composition and function of the gut microbiota with CRC, but this relationship in low- and middle-income countries including Vietnam (with an estimated population of 100.3 million people in 2023, ranking 16th largest country by population in the world) is not well-explored. We collected clinical data and fecal samples from 43 CRC patients and 44 healthy control subjects. The total community DNA of microorganisms was extracted from the fecal samples and analyzed for microbiota composition using Illumina MiSeq amplicon sequencing targeting the V3-V4 region of the 16S rRNA gene. We identified a significant difference in the overall fecal microbiota composition between CRC patients and healthy controls, and we detected several CRC-associated microbial signatures in fecal samples of Vietnamese patients with CRC, which overlapped with signatures from other countries and meta-analyses. Although patients with (n = 8) and without (n = 35) type 2 diabetes (T2D) exhibited distinct gut microbiota composition compared to healthy controls, increased relative abundances of putatively pathogenic species including Parvimonas micra, Peptostreptococcus stomatis, and Prevotella intermedia were consistent biomarkers for CRC. In contrast, several health-associated species were significantly depleted in CRC patients such as Lactobacillus johnsonii and Bifidobacterium longum in CRC/non-T2D patients, Ruminococcus species, Bacteroides uniformis, and Phascolarctobacterium faecium in CRC/T2D patients, and Butyricicoccus pullicaecorum in both CRC groups combined. Our findings confirm alterations in gut microbiota composition in CRC in a pilot Vietnamese cohort and highlight several gut microbial taxa that may have inhibitory or driver roles in CRC. This and future studies will enable the development of cancer diagnostics and treatment strategies for CRC in Vietnam, with a focus on targeting the microbiota.

The Human Nasal Microbiome: A Perspective Study During the SARS-CoV-2 Pandemic in Malta.

The human respiratory tract is colonized by a complex microbial community that helps maintain respiratory health and plays a crucial role in defending the host from infections. Respiratory viruses have been demonstrated to alter microbiota composition, resulting in opportunistic species expansion, and increasing the disease severity and host susceptibility to bacterial co-infections. This study aims to examine the compositional differences in the nasal microbiota between SARS-CoV-2-infected and non-infected patients. We conducted Oxford Nanopore full-length 16S rRNA sequencing on nasal swabs from 94 COVID-19 negative and 85 COVID-19 positive patients collected during the SARS-CoV-2 pandemic in Malta. Our analysis identified significant alpha and beta diversity differences in the nasal microbiota composition among our study groups. We observed a trend toward decreased microbial richness and evenness in the COVID-Positive cohort with and increased abundance of common nasal opportunistic species including Citrobacter koseri, Dolosigranulum pigrum, Haemophilus influenzae, Klebsiella pneumoniae, and Moraxella catarrhalis. The findings from this study are in line with previously published papers identifying key alterations in the nasal microbiota composition associated with SARS-CoV-2 infection. Understanding these microbiome-driven mechanisms could present novel prognostic markers or offer new approaches for disease prevention and treatment.

Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.

Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis

The liver makes bile, an aqueous solution critical for fat absorption, which is secreted into the duodenum. Despite extensive studies on bile salts, other components of bile are less well characterized. Here we used global metabolomic analysis on bile from specific-pathogen-free, germ-free, Citrobacter rodentium-infected or Listeria monocytogenes-infected mice and identified a metabolome of 812 metabolites that were altered by both microbiota and enteric infection. Hepatic transcriptomics identified enteric-infection-triggered pathways that probably underlie bile remodelling. Enteric infection increased levels of four dicarboxylates in bile, including itaconate. Analysis of Acod1−/− mice indicated that increased itaconate also increased tuft cell abundance, altered microbiota composition and function as detected by metagenomic analysis, and modulated host defence, leading to reduced Vibrio cholerae colonization. Our data suggest that enteric-infection-associated signals are relayed between the intestine and liver and induce transcriptional programmes that shape the bile metabolome, modifying the immunomodulatory and host defence functions of bile.

Effect of Dietary Concentrate-to-Forage Ratios During the Cold Season on Slaughter Performance, Meat Quality, Rumen Fermentation and Gut Microbiota of Tibetan Sheep.

This study aimed to investigate the effects of different dietary concentrate-to-forage ratios on slaughter performance, meat quality, rumen fermentation, rumen microbiota and fecal microbiota in Tibetan sheep. A total of sixty male Tibetan sheep were equally allocated into three dietary groups based on concentrate-to-forage ratios, i.e., 30:70 (C30), 50:50 (C50), and 70:30 (C70). Compared with the C30 group, sheep fed the C70 diet resulted in a higher (p < 0.05) slaughter live weight (SLW), hot carcass weight (HCW), dressing percentage (DP), eye muscle area, average daily gain (ADG), and ruminal total volatile fatty acids concentration and propionate molar proportion and lower (p < 0.05) shear force and cooking loss of meat, and ruminal acetate molar proportion and acetate:propionate ratio. Sheep in the C50 group exhibited a higher (p < 0.05) SLW, HCW, ADG, and ruminal propionate molar proportion and lower (p < 0.05) shear force and cooking loss of meat, and ruminal acetate molar proportion and acetate: propionate ratio compared with the C30 group. In rumen fluid, the relative abundance of Butyrivibrio was lower (p = 0.031) in the C30 group, and that of Ruminococcus was higher (p = 0.003) in the C70 group compared with the C50 group. In feces, genus Monoglobus and UCG_002 were the most abundant in the C30 group (p < 0.05), and the relative abundance of Prevotella was significantly higher in the C70 group than in other groups (p = 0.013). Correlation analysis revealed possible links between slaughter performance and meat quality and altered microbiota composition in the rumen and feces of Tibetan sheep. Overall, feeding a C70 diet resulted in superior carcass characteristics and meat quality in Tibetan sheep, thus laying a theoretical basis for the application of short-term remote feeding during the cold season.

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

SARS-CoV-2 variants mediated tissue-specific metabolic reprogramming determines the disease pathophysiology in a hamster model

Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between tissues and SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed the presence of increased SARS-CoV-2 genomic RNA in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.

Yeast β-glucan supplementation lowers insulin resistance without altering microbiota composition compared with placebo in subjects with type II diabetes: a phase I exploratory study.

The increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre 'Western diets'. Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinaemia and insulin resistance in a murine model. Here, we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition, while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2·5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance compared with the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher fecal concentrations of several bile acids were detected in the treatment group when compared with the placebo after 8 weeks. These included tauroursodeoxycholic acid, which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in fecal microbiota composition or short-chain fatty acid levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.

Bioactive metabolites: A clue to the link between MASLD and CKD?

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Association between salivary microbiota and tacrolimus pharmacokinetic variability in kidney transplant

Kidney transplantation (KT) serves as a highly effective treatment for end-stage renal disease (ESRD). Nonetheless, the administration of tacrolimus, a commonly used immunosuppressant in KT, faces challenges due to the lack of dependable biomarkers for its efficacy and the considerable variability in tacrolimus pharmacokinetics (TacIPV). In this study, 183 saliva samples from 48 KT recipients under tacrolimus therapy, alongside 9 healthy control samples, were subjected to 16S rRNA sequencing. The analysis revealed significant differences in the composition of salivary microbiota among KT recipients, patients with ESRD, and healthy controls. Moreover, trough blood concentrations (C0) of tacrolimus were associated with alterations in microbiota composition. Notably, Capnocytophage consistently exhibited a negative correlation in both group-level and individual trends. Furthermore, distinct taxa were identified that effectively distinguished recipients with varying TacIPV, as demonstrated by a cross-validation random forest model (mean AUC = 0.7560), with Anaerolinea emerging as a prominent contributor to the classifier. These findings suggest that salivary microbiota is closely linked to tacrolimus C0 levels and could aid clinicians in differentiating KT recipients based on TacIPV.

Bacteroides vesicles promote functional alterations in the gut microbiota composition.

Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations in the gut microbiota composition. Bacteroides fragilis, which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate the inflammatory response and possibly alter the microbiota composition. In this study, we created a murine model of chronic sodium dextran sulfate (DSS)-induced intestinal colitis and treated it with B. fragilis OMVs. We monitored the efficiency of OMV therapy by determining the disease activity index (DAI) and performing histological examination (HE) of the intestine before and after vesicle exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compound composition in the animals' stools by HS-GC/MS to assess the functional activity of the microbiota. We observed more effective intestinal repair after OMV treatment according to the DAI and HE. A metabolomic study also revealed changes in the functional activity of the microbiota, with a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS and the group treated with OMVs (DSS OMVs). We also observed a positive correlation of these metabolites with Saccharibacteria and Acetivibrio in the control group, whereas in the DSS group, there was a negative correlation of phenol and pentanoic acid with Lactococcus and Romboutsia. According to the metabolome and sequencing data, the microbiota composition of the DSS-treated OMV group was intermediate between that of the control and DSS groups. OMVs not only have an anti-inflammatory effect but also contribute to the recovery of the microbiota composition.IMPORTANCEBacteroides fragilis vesicles contain superficially localized polysaccharide A (PSA), which has unique immune-modulating properties. Isolated PSA can prevent chemically induced colitis in a murine model. Outer membrane vesicles (OMVs) also contain digestive enzymes and volatile metabolites that can complement the anti-inflammatory properties of PSA. OMVs showed high therapeutic activity against sodium dextran sulfate-induced colitis, as confirmed by histological assays. 16S rRNA sequencing of fecal samples from different inflammatory stages, supplemented with comprehensive metabolome analysis of volatile compounds conducted by HS-GC/MS, revealed structural and functional alterations in the microbiota composition under the influence of OMVs. Correlation analysis of the OMV-treated and untreated experimental animal groups revealed associations of phenol and pentanoic acid with Lactococcus, Romboutsia, Saccharibacteria, and Acetivibrio.

Garlic-Induced Enhancement of Bifidobacterium: Enterotype-Specific Modulation of Gut Microbiota and Probiotic Populations

The gut microbiome is a dynamic ecosystem crucial for maintaining its host’s health by regulating various immune and metabolic functions. Since diet plays a fundamental role in shaping the gut microbiome, understanding the relationship between food consumption and microbiome structure is essential. Although medicinal plants are widely recognized for their broad health benefits, their specific impact on the gut microbiome remains unclear. In this study, we investigated the effects of garlic (Allium sativum) on the gut microbiome using an in vitro human fecal incubation model. Our findings revealed that the impact of garlic on gut microbial structure varied depending on the dominant gut microbiome components (enterotypes). The Bacteroides-dominant enterotype exhibited significant changes in overall microbial diversity in response to garlic, while the Prevotella-dominant enterotype remained unaffected. Additionally, the garlic treatment led to specific alterations in microbiota composition, such as an increase in beneficial probiotics like Bifidobacterium. We validated garlic’s prebiotic potential by promoting the growth of Bifidobacterium adolescentis under in vitro culture conditions. Our study highlights the importance of understanding enterotype-specific responses to diet and suggests that garlic may serve as a dietary supplement for modulating gut microbiota and promoting the growth of beneficial probiotics.

Dysbiosis-activated IL-17-producing T cells promote skin immunopathological progression in mice deficient of the Notch ligand Jag1 in keratinocytes

BackgroundThe Notch signaling pathway is an evolutionarily conserved regulatory cascade critical in skin development and homeostasis. Mice deficient of Notch signaling molecules have impaired skin and hair follicle development associated with local tissue inflammation. However, mechanisms underlying skin inflammation and pathology resulting from defective Notch signals are not well understood. ObjectiveTo dissect molecular and cellular mechanisms underlying development of skin immunopathology in mice defective of the Notch ligand Jagged-1 (Jag1). MethodsWe assessed involvement of microbiota and immune cell subsets in skin pathogenic symptoms in Foxn1CreJag1fl/fl mice that were deficient of Jag1 in keratinocytes. We also used RNA-seq and 16S rRNA gene-seq analyses to identify molecular factors and bacterial species contributing to skin pathologic symptoms in Foxn1CreJag1fl/fl mice. ResultsCompared to Jag1-sufficient littermate control mice, Foxn1CreJag1fl/fl mice had specific expansion of IL-17a-producing T cells accompanying follicular and epidermal hyperkeratosis and cyst formation while antibody blockage of IL-17a reduced the skin pathology. RNA-sequencing and 16S rRNA gene-sequencing analyses revealed dysregulated immune responses and altered microbiota compositions in the skin of Foxn1CreJag1fl/fl mice. Antibiotic treatment completely prevented over-activation of IL-17a-producing T cells and alleviated skin pathology in Foxn1CreJag1fl/fl mice. ConclusionDysbiosis-induced over-activation of IL-17a-producing T cells is critically involved in development of skin pathology in Foxn1CreJag1fl/fl mice, establishing Foxn1CreJag1fl/fl mice as a useful model to study pathogenesis and therapeutic targets in microbiota-IL-17-mediated skin inflammatory diseases such as hidradenitis suppurativa (HS) and psoriasis.

The kynurenine pathway regulated by intestinal innate lymphoid cells mediates postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is a prevalent neurological complication that can impair learning and memory for days, months, or even years after anesthesia/surgery. POCD is strongly associated with an altered composition of the gut microbiota (dysbiosis), but the accompanying metabolic changes and their role in gut–brain communication and POCD pathogenesis remain unclear. Here, the present study reports that anesthesia/surgery in aged mice induces elevated intestinal indoleamine 2,3-dioxygenase (IDO) expression and activity, which shifts intestinal tryptophan (TRP) metabolism toward more IDO-catalyzed kynurenine (KYN) and less gut bacteria-catabolized indoleacetic acid (IAA). Both anesthesia/surgery and intraperitoneal KYN administration induce increased KYN levels that correlate with impaired spatial learning and memory, whereas dietary IAA supplementation attenuates the anesthesia/surgery-induced cognitive impairment. Mechanistically, anesthesia/surgery increases interferon-γ (IFN-γ)-producing group 1 innate lymphoid cells (ILC1) in the small intestine lamina propria and elevates intestinal IDO expression and activity, as indicated by the higher ratio of KYN to TRP. The IDO inhibitor 1-MT and antibodies targeting IFN-γ or ILCs mitigate anesthesia/surgery-induced cognitive dysfunction, suggesting that intestinal ILC1 expansion and the ensuing IFN-γ-induced IDO upregulation may be the primary pathway mediating the shift to the KYN pathway in POCD. The ILC1–KYN pathway in the intestine could be a promising therapeutic target for POCD.

The Influence of the Protozoan Giardia lamblia on the Modulation of the Immune System and Alterations in Host Glucose and Lipid Metabolism.

Giardia lamblia, the cause of giardiasis, significantly impacts patients with metabolic disorders related to insulin resistance (IR). Both giardiasis and metabolic disorders share elements such as chronic inflammation and intestinal dysbiosis, which substantially affect the metabolic and cytokine profiles of patients. This review discusses the mechanisms of virulence of G. lamblia, its influence on the immune system, and its association with metabolic disorders. The review aims to show how G. lamblia invasion acts on the immune system and the glucose and lipid metabolism. Key findings reveal that G. lamblia infection, by disrupting intestinal permeability, alters microbiota composition and immune responses, potentially impairing metabolic status. Future research should focus on elucidating the specific mechanisms by which G. lamblia influences the metabolism, exploring the long-term consequences of chronic infection, and developing targeted therapeutic strategies that include both parasitic and metabolic aspects. These insights underscore the need for a multidisciplinary approach to the treatment of giardiasis in patients with metabolic disorders.

Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome

Ethnopharmacological relevanceUlcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. Aim of the studyThe goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. Materials and methodsTo investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. ResultsFLZP contains 109 components, including liquiritin (584.8176 μg/g), benzoylaconine (16.3087 μg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 μg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. ConclusionsFLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.