Gut Microbial Features Research Articles

Gut microbial and metabolic features associated with Clostridioides difficile infection recurrence in children

Abstract Background Recurrent Clostridioides difficile (C. difficile) infection (rCDI) is a critical clinical issue due to the increase in incidence and difficulty in treatment. We aimed to identify gut microbial and metabolic features associated with disease recurrence in a group of pediatric CDI patients. Methods A total of 84 children with primary CDI were prospectively enrolled in the study. Fecal samples collected at the initial diagnosis were subjected to 16S rRNA gene sequencing and targeted metabolomics analysis to profile the bacterial composition and metabolome. Results Twenty-six (26/84, 31.0%) pediatric CDI patients experienced recurrence. The alpha diversity of the fecal microbiota was significantly lower in the recurrent group than in the nonrecurrent group, and the beta diversity was different from that of the nonrecurrent group. Taxonomic profiles revealed that the relative abundances of multiple bacterial taxa significantly differed between the recurrent and nonrecurrent groups. Linear discriminant analysis (LDA) effect size (LEfSe) analysis identified several bacterial genera that discriminated between recurrent and nonrecurrent groups, including Parabacteroides, Coprococcus, Disalister and Clostridium. Recurrent bacteria presented lower abundances of several short-chain fatty acid (SCFA)-producing bacteria (Faecalibacterium, Butyricicoccus, Clostridium, Roseburia, and Ruminococcus), which were correlated with reduced fecal SCFA levels. In addition, several bile acids (BAs), including lithochalic acid (LCA), 12-ketoLCA, trihydroxycholestanoic acid (3-DHCA), and deoxycholic acid (DCA), were decreased in recurrent patients. Conclusions Our study suggests that the differing gut microbiota profiles in pediatric CDI patients may contribute to disease recurrence by modulating SCFA concentrations and BA profiles. The gut microbiota and metabolite signatures may be used to predict disease recurrence in children with CDI.

The compositional and functional imbalance of the gut microbiota in CKD linked to disease patterns

BackgroundThe prevalence of chronic kidney disease (CKD) is on the rise, posing a significant public health challenge. Although gut microbiome dysbiosis has been implicated in the impairment of kidney functions, the existence of pathological subtypes-linked differences remains largely unknown. We aimed to characterize the intestinal microbiota in patients with membranous nephropathy (MN), IgA nephropathy (IgAN), minimal change disease (MCD), and ischemic renal injury (IRI) in order to investigate the intricate relationship between intestinal microbiota and CKD across different subtypes.MethodsWe conducted a cross-sectional study involving 94 patients with various pathological patterns of CKD and 54 healthy controls (HCs). The clinical parameters were collected, and stool samples were obtained from each participant. Gut microbial features were analyzed using 16S rRNA sequencing and taxon annotation to compare the HC, CKD, MN, IgAN, MCD, and IRI groups.ResultsThe CKD subjects exhibited significantly reduced alpha diversity, modified community structures, and disrupted microbial composition and potential functions compared to the control group. The opportunistic pathogen Klebsiella exhibited a significant enrichment in patients with CKD, whereas Akkermansia showed higher abundance in HCs. The study further revealed the presence of heterogeneity in intestinal microbial signatures across diverse CKD pathological types, including MN, IgAN, MCD, and IRI. The depression of the family Lachnospiraceae and the genus Bilophila was prominently observed exclusively in patients with MN, while suppressed Streptococcus was detected only in individuals with MCD, and a remarkable expansion of the genus Escherichia was uniquely found in cases of IRI. The study also encompassed the development of classifiers employing gut microbial diagnostic markers to accurately discriminate between distinct subtypes of CKD.ConclusionsThe dysregulation of gut microbiome was strongly correlated with CKD, exhibiting further specificity towards distinct pathological patterns. Our study emphasizes the significance of considering disease subtypes when assessing the impact of intestinal microbiota on the development, diagnosis, and treatment of CKD.

An Empirical Dietary Pattern Associated With the Gut Microbial Features in Relation to Colorectal Cancer Risk

Background & AimsEpidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited. MethodsLeveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks+Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF) status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-up Study (1986-2018), Nurses’ Health Study (NHS) (1984-2020), and NHS II (1991-2019). ResultsThe CMDS was characterized by high industrially processed foods and low unprocessed fiber-rich foods intakes. In 259,200 participants, we documented 3,854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (Ptrend<0.001), with a multivariable hazard ratio (HRQ5vs.Q1) of 1.25 (95%CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, e.g., the Western and prudent diets. Notably, the association was stronger for tumoral F. nucleatum-positive (HRQ5vs.Q1, 2.51; 95%CI, 1.68-3.75; Ptrend<0.001) (Pheterogeneity=0.03, positivity vs. negativity), pks+E. coli-positive (HRQ5vs.Q1, 1.68; 95%CI, 0.84-3.38; Ptrend=0.005) (Pheterogeneity=0.01, positivity vs. negativity), and ETBF-positive CRC (HRQ5vs.Q1, 2.06; 95%CI, 1.10-3.88; Ptrend=0.016) (Pheterogeneity=0.06, positivity vs. negativity), compared with their negative counterparts. ConclusionsCMDS was associated with increased CRC risk, especially for tumors with detectable F. nucleatum, pks+E. coli, and ETBF in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC.

Gut microbial features and circulating metabolomic signatures of frailty in older adults.

Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62-96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic data. We identified 18 microbial species and 17 metabolites shifted along with frailty severity, with stronger links observed in females. The associations of nine species, including various Clostridium species and Faecalibacterium prausnitzii, with FI were reproducible in two external populations. Plasma glycerol levels, white blood cell count and kidney function partially mediated these associations. A composite microbial score derived from FI significantly predicted 2-year mortality (adjusted hazard ratio across extreme quartiles, 2.86; 95% confidence interval, 1.38-5.93), highlighting the potential of microbiota-based strategies for risk stratification in older adults.

Exploring the impact of gut microbiota on liver health in mice and patients with Wilson disease.

Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury. Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries. Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury. Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury.

Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes.

The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D.

Gut microbial features and dietary fiber intake predict gut microbiota response to resistant starch supplementation

ABSTRACT Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation. We enrolled 76 healthy adults into a 7-week crossover study with 59 individuals completing the study. Participants consumed RS type 2 (RS2), RS type 4 (RS4), and digestible starch, for 10 d each with 5-d washout periods in between. We collected fecal and saliva samples and food records during each treatment period. We performed 16S rRNA gene sequencing and measured fecal short-chain fatty acids (SCFAs), salivary amylase (AMY1) gene copy number, and salivary amylase activity (SAA). Dietary fiber intake was predictive of the relative abundance of several amplicon sequence variants (ASVs) at the end of both RS treatments. AMY1-related metrics were not predictive of response to RS. SAA was only predictive of the relative abundance of one ASV after digestible starch supplementation. Interestingly, SCFA concentrations increased the most during digestible starch supplementation. Treatment order (the order of consumption of RS2 and RS4), alpha diversity, and a subset of ASVs were predictive of SCFA changes after RS supplementation. Based on our findings, dietary fiber intake and gut microbiome composition would be informative if assessed prior to recommending RS supplementation because these data can be used to predict changes in specific ASVs and fecal SCFA concentrations. These findings lay a foundation to support the premise that using a precision nutrition approach to optimize the benefits of dietary fibers such as RS could be an effective strategy to compensate for the low consumption of dietary fiber nationwide.

A pilot case-control study on the fecal microbiota of pediatric functional abdominal pain-not otherwise specified and the role of early life stress.

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients (n = 40) were compared to healthy controls (n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations.

Transgenerational effects of early life stress on the fecal microbiota in mice

Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life, including abundance of eight amplicon sequencing variants (ASVs). Further effects on fecal microbial composition, structure (weighted Jaccard index), and abundance of 16 ASVs are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring.

Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease

We aimed to identify gut microbial features in Parkinson’s disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls in Japan with five previously reported datasets from USA, Germany, China1, China2, and Taiwan. GC-MS and LC-MS/MS assays were established to quantify fecal short-chain fatty acids (SCFAs) and fecal polyamines, respectively. α-Diversity was increased in PD across six datasets. Taxonomic analysis showed that species Akkermansia muciniphila was increased in PD, while species Roseburia intestinalis and Faecalibacterium prausnitzii were decreased in PD. Pathway analysis showed that genes in the biosyntheses of riboflavin and biotin were markedly decreased in PD after adjusting for confounding factors. Five out of six categories in carbohydrate-active enzymes (CAZymes) were decreased in PD. Metabolomic analysis of our fecal samples revealed that fecal SCFAs and polyamines were significantly decreased in PD. Genes in the riboflavin and biotin biosyntheses were positively correlated with the fecal concentrations of SCFAs and polyamines. Bacteria that accounted for the decreased riboflavin biosynthesis in Japan, the USA, and Germany were different from those in China1, China2, and Taiwan. Similarly, different bacteria accounted for decreased biotin biosynthesis in the two country groups. We postulate that decreased SCFAs and polyamines reduce the intestinal mucus layer, which subsequently facilitates the formation of abnormal α-synuclein fibrils in the intestinal neural plexus in PD, and also cause neuroinflammation in PD.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization

BackgroundVaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels.MethodsWe conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses.ResultsThe MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features.ConclusionsThe human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Distinguishing bipolar depression, bipolar mania, and major depressive disorder by gut microbial characteristics.

Gut microbial disturbance has been widely confirmed in mood disorders. However, little is known about whether gut microbial characteristics can distinguish major depressive disorder (MDD), bipolar depression (BP-D), and bipolar mania (BP-M). This was a prospective case-control study. The composition of gut microbiota was profiled using 16S ribosomal RNA (rRNA) gene sequencing of fecal samples and compared between healthy controls (HC; n = 46), MDD (n = 51), BP-D (n = 44), and patients with BP-M (n = 45). Gut microbial compositions were remarkably changed in the patients with MDD, BP-D, and BP-M. Compared to HC, distinct gut microbiome signatures were found in MDD, BP-D, and BP-M, and some gut microbial changes were overlapping between the three mood disorders. Furthermore, we identified a signature of 7 operational taxonomic units (OUT; Prevotellaceae-related OUT22, Prevotellaceae-related OUT31, Prevotellaceae-related OTU770, Ruminococcaceae-related OUT70, Bacteroidaceae-related OTU1536, Propionibacteriaceae-related OTU97, Acidaminococcaceae-related OTU34) that can distinguish patients with MDD from those with BP-D, BP-M, or HC, with area under the curve (AUC) values ranging from 0.910 to 0.996. Our results provide the clinical rationale for the discriminative diagnosis of MDD, BP-D, and BP-M by characteristic gut microbial features.

Associations Between Gut Microbial Features and Sickness Symptoms in Kidney Transplant Recipients.

The study investigated the relationship of gut microbiome features and sickness symptoms in kidney transplant recipients. Employing a prospective, longitudinal design, we collected data from 19 participants who had undergone living-donor kidney transplant at three timepoints (pre-transplant and 1week and 3months post-transplant). Sickness symptom data and fecal specimens were collected at each timepoint. Participants were grouped either as high or low sickness symptom severity at baseline. Shotgun metagenomics sequencing characterized gut microbial structure and functional gene content. Fecal microbial features, including alpha (evenness and richness within samples) and beta (dissimilarities between samples) diversity and relative abundances, were analyzed using R statistical packages. Cross-sectional and longitudinal analyses examined relationships between gut microbial features and sickness symptoms. Although our exploratory findings revealed no significant differences in alpha and beta diversity between groups, the high-severity group showed lower microbial richness and evenness than the low-severity group. The high-severity group had enriched relative abundance of bacteria from the genera Citrobacter and Enterobacter and reduced relative abundance of bacteria from the genus Akkermansia across timepoints. No functional genes differed significantly between groups or timepoints. Kidney transplant recipients with high symptom burden displayed increased putative proinflammatory bacteria and decreased beneficial bacteria. This study provides an effect size that future large cohort studies can employ to confirm associations between gut microbial features and sickness symptom experiences in the kidney transplant population. The study findings also have implications for future interventional studies aiming to alleviate the sickness symptom burden in this population.

Uncovering specific taxonomic and functional alteration of gut microbiota in chronic kidney disease through 16S rRNA data.

Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.

The menopause-related gut microbiome: associations with metabolomics, inflammatory protein markers, and cardiometabolic health in women with HIV.

This study aimed to identify menopause-related gut microbial features, as well as their related metabolites and inflammatory protein markers, and link with cardiometabolic risk factors in women with and without HIV. In the Women's Interagency HIV Study, we performed shotgun metagenomic sequencing on 696 stool samples from 446 participants (67% women with HIV), and quantified plasma metabolomics and serum proteomics in a subset (~86%). We examined the associations of menopause (postmenopausal vs premenopausal) with gut microbial features in a cross-sectional repeated-measures design and further evaluated those features in relation to metabolites, proteins, and cardiometabolic risk factors. Different overall gut microbial composition was observed by menopausal status in women with HIV only. We identified a range of gut microbial features that differed between postmenopausal and premenopausal women with HIV (but none in women without HIV), including abundance of 32 species and functional potentials involving 24 enzymatic reactions and lower β-glucuronidase bacterial gene ortholog. Specifically, highly abundant species Faecalibacterium prausnitzii , Bacteroides species CAG:98 , and Bifidobacterium adolescentis were depleted in postmenopausal versus premenopausal women with HIV. Menopause-depleted species (mainly Clostridia ) in women with HIV were positively associated with several glycerophospholipids, while negatively associated with imidazolepropionic acid and fibroblast growth factor 21. Mediation analysis suggested that menopause may decrease plasma phosphatidylcholine plasmalogen C36:1 and C36:2 levels via reducing abundance of species F. prausnitzii and Acetanaerobacterium elongatum in women with HIV. Furthermore, waist-to-hip ratio was associated with menopause-related microbes, metabolites, and fibroblast growth factor 21 in women with HIV. Menopause was associated with a differential gut microbiome in women with HIV, related to metabolite and protein profiles that potentially contribute to elevated cardiometabolic risk.

OBMeta: a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases.

Gut dysbiosis is closely associated with obesity and related metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The gut microbial features and biomarkers have been increasingly investigated in many studies, which require further validation due to the limited sample size and various confounding factors that may affect microbial compositions in a single study. So far, it lacks a comprehensive bioinformatics pipeline providing automated statistical analysis and integrating multiple independent studies for cross-validation simultaneously. OBMeta aims to streamline the standard metagenomics data analysis from diversity analysis, comparative analysis, and functional analysis to co-abundance network analysis. In addition, a curated database has been established with a total of 90 public research projects, covering three different phenotypes (Obesity, T2D, and NAFLD) and more than five different intervention strategies (exercise, diet, probiotics, medication, and surgery). With OBMeta, users can not only analyze their research projects but also search and match public datasets for cross-validation. Moreover, OBMeta provides cross-phenotype and cross-intervention-based advanced validation that maximally supports preliminary findings from an individual study. To summarize, OBMeta is a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases. OBMeta is freely available at: http://obmeta.met-bioinformatics.cn/.

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.

The gut microbiota as a potential biomarker for methamphetamine use disorder: evidence from two independent datasets.

Methamphetamine use disorder (MUD) poses a considerable public health threat, and its identification remains challenging due to the subjective nature of the current diagnostic system that relies on self-reported symptoms. Recent studies have suggested that MUD patients may have gut dysbiosis and that gut microbes may be involved in the pathological process of MUD. We aimed to examine gut dysbiosis among MUD patients and generate a machine-learning model utilizing gut microbiota features to facilitate the identification of MUD patients. Fecal samples from 78 MUD patients and 50 sex- and age-matched healthy controls (HCs) were analyzed by 16S rDNA sequencing to identify gut microbial characteristics that could help differentiate MUD patients from HCs. Based on these microbial features, we developed a machine learning model to help identify MUD patients. We also used public data to verify the model; these data were downloaded from a published study conducted in Wuhan, China (with 16 MUD patients and 14 HCs). Furthermore, we explored the gut microbial features of MUD patients within the first three months of withdrawal to identify the withdrawal period of MUD patients based on microbial features. MUD patients exhibited significant gut dysbiosis, including decreased richness and evenness and changes in the abundance of certain microbes, such as Proteobacteria and Firmicutes. Based on the gut microbiota features of MUD patients, we developed a machine learning model that demonstrated exceptional performance with an AUROC of 0.906 for identifying MUD patients. Additionally, when tested using an external and cross-regional dataset, the model achieved an AUROC of 0.830. Moreover, MUD patients within the first three months of withdrawal exhibited specific gut microbiota features, such as the significant enrichment of Actinobacteria. The machine learning model had an AUROC of 0.930 for identifying the withdrawal period of MUD patients. In conclusion, the gut microbiota is a promising biomarker for identifying MUD and thus represents a potential approach to improving the identification of MUD patients. Future longitudinal studies are needed to validate these findings.

Palmitoylethanolamide counteracts high-fat diet-induced gut dysfunction by reprogramming microbiota composition and affecting tryptophan metabolism.

Obesity is associated with gastrointestinal (GI) tract and central nervous system (CNS) disorders. High-fat diet (HFD) feeding-induced obesity in mice induces dysbiosis, causing a shift toward bacteria-derived metabolites with detrimental effects on metabolism and inflammation: events often contributing to the onset and progression of both GI and CNS disorders. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with beneficial effects in mouse models of GI and CNS disorders. However, the mechanisms underlining its enteroprotective and neuroprotective effects still need to be fully understood. Here, we aimed to study the effects of PEA on intestinal inflammation and microbiota alterations resulting from lipid overnutrition. Ultramicronized PEA (30 mg/kg/die per os) was administered to HFD-fed mice for 7 weeks starting at the 12th week of HFD regimen. At the termination of the study, the effects of PEA on inflammatory factors and cells, gut microbial features and tryptophan (TRP)-kynurenine metabolism were evaluated. PEA regulates the crosstalk between the host immune system and gut microbiota via rebalancing colonic TRP metabolites. PEA treatment reduced intestinal immune cell recruitment, inflammatory response triggered by HFD feeding, and corticotropin-releasing hormone levels. In particular, PEA modulated HFD-altered TRP metabolism in the colon, rebalancing serotonin (5-HT) turnover and reducing kynurenine levels. These effects were associated with a reshaping of gut microbiota composition through increased butyrate-promoting/producing bacteria, such as Bifidobacterium, Oscillospiraceae and Turicibacter sanguinis, with the latter also described as 5-HT sensor. These data indicate that the rebuilding of gut microbiota following PEA supplementation promotes host 5-HT biosynthesis, which is crucial in regulating intestinal function.

Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease.

Anaemia of chronic disease (ACD) is the second most common type of anaemia and lacks an effective treatment. Patients with anaemia are reported to have altered gut microbial profiles, which may affect erythropoiesis. Here, we investigated the gut microbial features of patients with ACD and determined whether regulating gut microbiota using washed microbiota transplantation (WMT) was effective in treating ACD. We compared the gut microbiota profile of patients with ACD and healthy controls, evaluated the efficacy of WMT on haematological parameters in the patients, and analysed the alterations in gut microbiota after WMT treatment. Patients with ACD had lower gut microbial richness, and differences in microbial composition and function, relative to healthy controls. Additionally, the relative abundances of two butyrate-producing genera Lachnospiraceae NK4A136 group and Butyricicoccus, were positively correlated with the haemoglobin (HGB) level and lower in patients with ACD than controls. WMT significantly increased HGB levels in patients with ACD. After the first, second and third WMT rounds, normal HGB levels were restored in 27.02%, 27.78% and 36.37% (all p < .05) of patients with ACD, respectively. Moreover, WMT significantly increased the abundance of butyrate-producing genera and downregulated gut microbial functions that were upregulated in patients with ACD. Patients with ACD exhibited differences in gut microbial composition and function relative to healthy controls. WMT is an effective treatment for ACD that reshapes gut microbial composition, restores butyrate-producing bacteria and regulates the functions of gut microbiota.