Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy.

BACKGROUND: Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified. METHODS: We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing. RESULTS: Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria-Gammaproteobacteria-Enterobacteriales-Enterobacteriaceae-Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN. CONCLUSION: Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

Bacterial diversity associated with the abdomens of naturally Plasmodium-infected and non-infected Nyssorhynchus darlingi.

BACKGROUND: The bacterial community present in the abdomen in Anophelinae mosquitoes can influence mosquito susceptibility to Plasmodium infection. Little is known about the bacteria associated with Nyssorhynchus darlingi, a primary malaria vector in the Amazon basin. We investigated the abdominal bacterial community compositions of naturally Plasmodium-infected (P-positive, n = 9) and non-infected (P-negative, n = 7) Ny. darlingi from the Brazilian Amazon region through massive parallel sequencing of the bacterial V4 variable region of the 16S rRNA gene. RESULTS: Bacterial richness of Ny. darlingi encompassed 379 operational taxonomic units (OTUs), the majority of them belonging to the Proteobacteria, Firmicutes and Bacteroides phyla. Escherichia/Shigella and Pseudomonas were more abundant in the P-positive and P-negative groups, respectively, than in the opposite groups. Enterobacter was found only in the P-negative group. The results of statistical analyses conducted to compare bacterial abundance and diversity between Plasmodium-infected and Plasmodium-non-infected mosquitoes were not significant. CONCLUSIONS: This study increased knowledge about bacterial composition in Ny. darlingi and revealed that Plasmodium-positive and Plasmodium-negative groups share a common core of bacteria. The genera Prevotella 9, Sphingomonas, Bacteroides, and Bacillus were reported for the first time in Ny. darlingi.

The effect of antibiotic cocktails on host immune status is dynamic and does not always correspond to changes in gut microbiota.

The disruption of the gut microbiota by treatment with an antibiotic cocktail (ABx) can trigger an imbalance in immune homeostasis. However, whether the changes in the intestinal microbiota always correspond to the changes in the physiology and immune homeostasis of the host remains unclear. Here, we analyzed the effects of ABx on immune homeostasis by analyzing the colonic transcriptome with 16S rRNA analysis of the gut microbiota on the 7th and 21st days of continuous treatment with ABx. Our results showed that the composition profile of the gut microbiota was similar after 7 and 21 days of ABx treatment. However, after 21 days of ABx treatment, the intestinal inflammation did not deteriorate further. Instead, the inflammation of the host was relieved, and half of the differentially expressed genes in the colon were restored compared with the 7 days of ABx treatment. Furthermore, the enrichment and network analysis of these restored genes indicated that expression of regenerating islet-derived protein 3ß (Reg3b) and expression of regenerating islet-derived protein 3γ (Reg3g), especially Reg3b, may participate in the regulation of the inflammatory response and affect the changes in host immune homeostasis during continuous ABx treatment. Finally, Spearman's correlation analysis showed that the expression of Reg3b is correlated with the growth of Escherichia-Shigella. Our data demonstrated that even though the disruption of the gut microbiota profile induced by ABx treatment is similar, the host response and immune status will be different at different times.Key Points• Host immune status can change in different ABx treatment times.• Gut microbiota showed same exhaustion state in different ABx treatment times.• Host tried to revert to a certain extent after long-term ABx treatment.• Reg3b may affect the changes in host immune homeostasis during continuous ABx treatment.• The expression of Reg3b correlated with the growth of Escherichia-Shigella.

A dual-function mixed-culture biofilm for sulfadiazine removal and electricity production using bio-electrochemical system.

Sulfadiazine (SDZ) is frequently detected in environmental samples, arousing much concern due to its toxicity and hard degradation. This study investigated the electricity generation capabilities, SDZ removal and microbial communities of a highly efficient mixed-culture system using repeated transfer enrichments in a bio-electrochemical system. The mixed-culture biofilm (S160-T2) produced a remarkable current density of 954.12 ± 15.08 µA cm-2 with 160 mg/L SDZ, which was 32.9 and 1.8 times higher than that of Geobacter sulfurreducens PCA with 40 mg/L SDZ and without additional SDZ, respectively. Especially, the impressive SDZ removal rate of 98.76 ± 0.79% was achieved within 96 h using the further acclimatized mixed-culture. The removal efficiency of this mixed-culture for SDZ through the bio-electrochemical system was 1.1 times higher than that using simple anaerobic biodegradation. Furthermore, the current density and removal efficiency in this system gradually decreased with increasing SDZ concentrations from 0 to 800 mg/L. In addition, community diversity data demonstrated that the dominant genera, Geobacter and Escherichia-Shigella, were enriched in mixed-culture biofilm, which might be responsible for the current production and SDZ removal. This work confirmed the important roles of acclimatized microbial consortia and co-substrates in the simultaneous removal of SDZ and electricity generation in an electrochemical system.

Changes in skin bacterial flora during the healing process of ulcer caused by self-destruction of lymph nodes due to tuberculous lymphadenitis.

An 86-year-old woman with residual left hemiplegia from a prior stroke, residing in a nursing facility, presented with swelling of the right side of her neck. Tuberculous lymphadenitis was diagnosed through polymerase chain reaction analysis and sputum culture, leading to treatment with isoniazid, rifampicin, and ethambutol. After 2 months, an abscess and ulcer formed; analysis of the bacterial flora of the ulcer revealed a Pseudomonas infection. Treatment with a topical iodine-containing ointment eradicated the Pseudomonas and led to increased diversity with the emergence of species from the Eukaryota and Archaea kingdoms. Subsequently, a loss of diversity occurred, ultimately resulting in a dominance of Escherichia-Shigella. We suggest that the bacterial flora of early ulcers may be dominated by multidrug-resistant Pseudomonas. Escherichia-Shigella may emerge during the ulcer healing process. We, therefore, strongly encourage recognition of the fact that individuals with tuberculosis are immunocompromised and emphasize the critical importance of early intervention in such infections.

Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.

Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery. IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.

Humoral immune responses primed by the alteration of gut microbiota were associated with galactose-deficient IgA1 production in IgA nephropathy.

Introduction: Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. Methods: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified. Results: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN. Conclusion: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.

Increased levels of Escherichia-Shigella and Klebsiella in the gut contribute to the responsivity of placebo analgesia.

Placebo analgesia is observed in both humans and animals. Given the complexity of placebo analgesia involving a variety of neurobiological, psychological, and psychosocial processes, further investigation into its underlying mechanisms is essential. Gut microbiota has been implicated in the responsivity of placebo analgesia, but its precise role remains unknown and warrants further investigations. Here, we conducted a conditioning training model with chronic inflammatory pain induced by complete Freund's adjuvant (CFA) in mice, associating parecoxib with different cues. Hierarchical clustering analysis of placebo analgesia behaviors was employed to classify mice into responders and non-responders phenotypes. Approximately 40% of CFA mice undergoing conditioning training exhibited placebo analgesia. Notably, placebo analgesia responders displayed reduced anxiety-like behaviors. 16S rRNA results revealed a distinct composition of gut microbiota composition among the control, placebo analgesia non-responders and responders groups. Notably, levels of Escherichia Shigella and Klebsiella in the gut were increased considerably in the placebo analgesia responders as compared to both control and non-responders groups. In conclusion, placebo analgesia responders demonstrated marked analgesia, reduced anxiety-like behaviors, and increased levels of Escherichia-Shigella and Klebsiella, implying a potential linkage between gut microbiota and placebo analgesia.

Changes in Gut Microbiota and Metabolites in Papillary Thyroid Carcinoma Patients Following Radioactive Iodine Therapy.

Purpose: Radioactive iodine therapy is administered through oral route, which is accumulated and absorbed in the intestine. However, its effects on the intestine remain unclear. In this study, we investigated the changes in the gut microbiota and metabolites following radioactive iodine therapy. Patients and Methods: A total of 76 stool samples from the same 38 patients were collected at the start of radioactive iodine therapy and three days following the therapy. Stool microbiota and metabolites were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Results: Enterobacteriales, Enterobacteriaceae and Escherichia-Shigella were elevated in most patients (27/38) following the therapy. The levels of 2-hydroxyundec-7-enoylcarnitine were significantly lower, whereas those of 5-dehydroavenasterol, butylisopropylamine, and salsoline-1-carboxylate were higher following the therapy. The relative abundance of Escherichia-Shigella was negatively correlated with 2-hydroxyundec-7-enoylcarnitine level (r2 = -0.661, P = 0.009). Functional pathways were predicted to be involved in amino acid and lipid metabolism following the therapy. Particularly, phenylalanine, linoleic acid, sphingolipid, purine, and alpha-linolenic acid metabolism were the main metabolic pathways. Conclusion: Gut microbiota was disturbed following radioactive iodine therapy, with increased Escherichia-Shigella. Processes associated with energy production seems to be impacted following the therapy, with significantly decreased 2-hydroxyundec-7-enoylcarnitine level. Meanwhile, some metabolites and functional pathways may have a positive effect on intestinal homeostasis, and may be related to the repair and promotion of gut recovery following the therapy. This study provides a basic foundation to explore how radioactive iodine affects gut microbiota and metabolites, and how gut function is regulated in response to radioactive iodine therapy.

Early-life gut microbiota in food allergic children and its impact on the development of allergic disease.

BACKGROUND: The prevalence of food allergies (FA) has been steadily increasing over 2 to 3 decades, showing diverse symptoms and rising severity. These long-term outcomes affect children's growth and development, possibly linking to inflammatory bowel disease. However, the cause remains unclear. Previous studies reveal that early infancy significantly impacts FA development through gut microbiota. Yet, a consistent view on dysbiosis characteristics and its connection to future allergies is lacking. We explored how early-life gut microbiota composition relates to long-term clinical signs in children with FA through longitudinal research. METHODS: We employed high-throughput 16S rDNA gene sequencing to assess gut microbiota composition in early-life FA children in southern Zhejiang. Follow-up of clinical manifestations over 2 years allowed us to analyze the impact of early-life gut microbiota dysbiosis on later outcomes. RESULTS: While the diversity of gut microbiota in FA children remained stable, there were shifts in microbiota abundance. Abundant Akkermansia, Parabacteroides, Blautia, and Escherichia-Shigella increased, while Bifidobacterium and Clostridium decreased. After 2 years, two of ten FA children still showed symptoms. These two cases exhibited increased Escherichia-Shigella and reduced Bifidobacterium during early childhood. The other eight cases experienced symptom remission. CONCLUSIONS: Our study suggests that FA and its prognosis might not correlate with early-life gut microbiota diversity. Further experiments are needed due to the small sample size, to confirm these findings.

Dietary fiber during gestation improves lactational feed intake of sows by modulating gut microbiota.

BACKGROUND: The feed intake of sows during lactation is often lower than their needs. High-fiber feed is usually used during gestation to increase the voluntary feed intake of sows during lactation. However, the mechanism underlying the effect of bulky diets on the appetites of sows during lactation have not been fully clarified. The current study was conducted to determine whether a high-fiber diet during gestation improves lactational feed intake (LFI) of sows by modulating gut microbiota. METHODS: We selected an appropriate high-fiber diet during gestation and utilized the fecal microbial transplantation (FMT) method to conduct research on the role of the gut microbiota in feed intake regulation of sows during lactation, as follows: high-fiber (HF) diet during gestation (n = 23), low-fiber (LF) diet during gestation (n = 23), and low-fiber diet + HF-FMT (LFM) during gestation (n = 23). RESULTS: Compared with the LF, sows in the HF and LFM groups had a higher LFI, while the sows also had higher peptide tyrosine tyrosine and glucagon-like peptide 1 on d 110 of gestation (G110 d). The litter weight gain of piglets during lactation and weaning weight of piglets from LFM group were higher than LF group. Sows given a HF diet had lower Proteobacteria, especially Escherichia-Shigella, on G110 d and higher Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus, on d 7 of lactation (L7 d). The abundance of Escherichia-Shigella was reduced by HF-FMT in numerically compared with the LF. In addition, HF and HF-FMT both decreased the perinatal concentrations of proinflammatory factors, such as endotoxin (ET), lipocalin-2 (LCN-2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). The concentration of ET and LCN-2 and the abundance of Proteobacteria and Escherichia-Shigella were negatively correlated with the LFI of sows. CONCLUSION: The high abundance of Proteobacteria, especially Escherichia-Shigella of LF sows in late gestation, led to increased endotoxin levels, which result in inflammatory responses and adverse effects on the LFI of sows. Adding HF during gestation reverses this process by increasing the abundance of Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus.

Cross-Sectional Study: New Approach for Diagnostic Identification of Non-Robust Older Adult.

SCOPE: The aging biomarkers are alternatives and none of them can act as a strong predictor of frailty during the progression of aging. Several studies reveal the relationship between metabolites and frailty or gut microbiota and frailty. However, the connection between metabolites and gut microbiota in non-robust older adults has not been discussed yet. The study aims to combine the findings of serum metabolites and gut microbiota in non-robust subjects as a possible diagnostic biomarker. METHODS AND RESULTS: Frailty-related assessments are conducted to ensure the discrimination of non-robustness. The serum and fecal are collected for serum metabolomics and gut microbiota analysis. Robust and non-robust subjects show very different gut microbial compositions. Among the gut microbial differences, Escherichia/Shigella and its higher taxonomic ranks are found to have the most discriminative abundance among compared groups. More importantly, the abundance of Escherichia/Shigella is found to be positively correlated (p < 0.05) with the level of discriminant metabolites, such as serum oxoglutarate, glutamic acid, and 1-methyladenosine. CONCLUSION: These results indicate the obvious interrelation between gut microbiota and serum metabolites in non-robust older adults. Besides, the findings suggest that Escherichia/Shigella can be a potential biomarker candidate for robustness sub-phenotypic identification.

The variation characteristics of fecal microbiota in remission UC patients with anxiety and depression.

Background: Ulcerative colitis (UC) patients with relapsed disease are most likely to suffer from anxiety and depression. Increasing data indicates that psychological issues can change the composition of intestinal flora. Thus, we aim to seek the variation of intestinal microbiota composition in remission UC patients with anxiety and depression in Northwest China. Results: In this study, 45 UC patients in remission were enrolled. The incidence of anxiety was 33.3%, and the prevalence of depression was 22.2%. There was no statistical difference in the alpha diversity of fecal microbiota, while beta diversity had a significant difference between the anxiety group and the non-anxiety group and the depression group and the non-depression group. Species composition analysis results showed that the ratio of Bifidobacterium and Lactobacilales significantly decreased. At the same time, the proportion of Escherichia-Shigella and Proteus_mirabilis increased in the anxiety group, and the ratio of Faecalibacterium and Bifidobacterium significantly decreased. In contrast, Escherichia-Shigella increased in the depression group at the gene levels. Conclusion: Anxiety and depression still exist in UC patients even in the remission period. We first identify that the proportion of probiotics decreases while the proportion of pathogens increases in UC patients with anxiety and depression. These findings may provide a new pathophysiological mechanism for the recurrence of disease caused by impaired psychological function and a new method for the treatment strategy of UC patients with psychological issues.

Predominance of Escherichia-Shigella in Gut Microbiome and Its Potential Correlation with Elevated Level of Plasma Tumor Necrosis Factor Alpha in Patients with Tuberculous Meningitis.

Tuberculous meningitis (TBM), the most lethal and disabling form of tuberculosis (TB), may be related to gut microbiota composition, warranting further study. Here we systematically compared gut microbiota compositions and blood cytokine profiles of TBM patients, pulmonary TB patients, and healthy controls. Notably, the significant gut microbiota dysbiosis observed in TBM patients was associated with markedly high proportions of Escherichia-Shigella species as well as increased blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Next, we obtained a fecal bacterial isolate from a TBM patient and administered it via oral gavage to mice in order to develop a murine gut microbiota dysbiosis model for use in exploring mechanisms underlying the observed relationship between gut microbial dysbiosis and TBM. Thereafter, cells of commensal Escherichia coli (E. coli) were isolated and administered to model mice by gavage and then mice were inoculated with Mycobacterium tuberculosis (M. tuberculosis). Subsequently, these mice exhibited increased blood TNF-α levels accompanied by downregulated expression of tight junction protein claudin-5, increased brain tissue bacterial burden, and elevated central nervous system inflammation relative to corresponding indicators in controls administered PBS by gavage. Thus, our results demonstrated that a signature dysbiotic gut microbiome profile containing a high proportion of E. coli was potentially associated with an increased circulating TNF-α level in TBM patients. Collectively, these results suggest that modulation of dysbiotic gut microbiota holds promise as a new strategy for preventing or alleviating TBM. IMPORTANCE As the most severe form of tuberculosis, the pathogenesis of tuberculous meningitis (TBM) is still unclear. Gut microbiota dysbiosis plays an important role in a variety of central nervous system diseases. However, the relationship between gut microbiota and TBM has not been identified. In our study, significant dysbiosis in gut microbiota composition with a high proportion of E. coli and increased levels of TNF-α in plasma was noted in TBM patients. A commensal E. coli was isolated and shown to increase the plasma level of TNF-α and downregulate brain tight junction protein claudin-5 in the murine model. Gavage administration of E. coli aggravated the bacterial burden and increased the inflammatory responses in the central nervous system after M. tuberculosis infection. Dysbiosis of gut microbiota may be a promising therapeutic target and biomarker for TBM prevention or treatment.

Alteration of Skin Microbiome in CKD Patients Is Associated With Pruritus and Renal Function.

Dysbiotic gut microbiome in chronic kidney disease (CKD) patients has been extensively explored in recent years. Skin microbiome plays a crucial role in patients with skin diseases or even systemic disorders. Pruritus is caused by the retention of uremic solutes in the skin. Until now, no studies have investigated the role of skin microbiome in CKD and its association with pruritus. Here, we aim to examine the bacterial profile of skin microbiome in CKD and whether it is correlated to pruritus. A total of 105 CKD patients and 38 healthy controls (HC) were recruited. Skin swab was used to collect skin samples at the antecubital fossa of participants. Bacterial 16S rRNA genes V3-V4 region was sequenced on NovaSeq platform. On the day of skin sample collection, renal function was assessed, and numeric rating scale was used to measure pruritus severity. Principal coordinate analysis (PCoA) revealed a significant difference in bacterial composition between the groups of CKD and HC. A depletion of bacterial diversity was observed in CKD patients. Akkermansia, Albimonas, Escherichia-Shigella, etc. showed significant higher abundance in CKD patients, whereas Flavobacterium, Blastomonas, Lautropia, etc. significantly declined in patients. Escherichia-Shigella achieved an acceptable diagnostic biomarker with area under the curve (AUC) value of 0.784 in the receiver operating characteristics (ROC) curve. In addition, CKD patients with pruritus (P-CKD) had a different bacterial community comparing to those without pruritus (non-P-CKD) and HC group. Several bacterial genera showing significant difference between P-CKD and non-P-CKD/HC, such as Oribacterium, significantly declined in P-CKD patients than that in the HC group, and Methylophaga significantly increased in P-CKD patients compared to that in HC subjects. Escherichia-Shigella was positively associated with the levels of pruritus severity, blood urea nitrogen (BUN), uric acid, and urine protein; Oribacterium was negatively associated with pruritus severity, whereas it was positively associated with estimated glomerular filtration rate (eGFR) and 24-h urine volume. The dysbiotic of skin microbiome in CKD patients and its association with pruritus and renal function shed a light on skin probiotics.

Comprehensive Analysis of the Relationships Between the Gut Microbiota and Fecal Metabolome in Individuals With Primary Sjogren's Syndrome by 16S rRNA Sequencing and LC-MS-Based Metabolomics.

The gut microbiota has been associated with primary Sjogren's syndrome (pSS), yet the biological implications of these associations are often elusive. We analyzed the fecal microbiota through 16S rRNA gene amplification and sequencing in 30 patients with pSS and 20 healthy controls (HCs); At the same time, the fecal metabolome was characterized by ultrahigh-performance liquid chromatography-mass spectrometry. In addition, correlation analyses of microbiota and metabolome data were performed to identify meaningful associations. We found that the microbiota composition of pSS patients was significantly different from that of HCs. The pSS gut microbiota is characterized by increased abundances of proinflammatory microbes, especially Escherichia-Shigella, and decreased abundances of anti-inflammatory microbes. Concerning the metabolome, a multivariate model with 33 metabolites efficiently distinguished cases from controls. Through KEGG enrichment analysis, we found that these metabolites were mainly involved in amino acid metabolism and lipid metabolism. The correlation analysis indicated that there were certain correlations between the microbiota and metabolism in pSS patients. In addition, an abundance of Escherichia-Shigella was found to be correlated with high levels of four metabolites (aflatoxin M1, glycocholic acid, L-histidine and phenylglyoxylic acid). Our research suggests that in pSS patients, the gut microbiota is characterized by a specific combination of proinflammatory changes and metabolic states. Escherichia-Shigella is a factor related to gut dysbiosis, which may promote intestinal damage and affect amino acid metabolism.

Gancao Xiexin Decoction Ameliorates Ulcerative Colitis in Mice via Modulating Gut Microbiota and Metabolites.

Purpose: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that starts with mucosal inflammation of the rectum and extends proximally in the colon in a continuous manner over a variable distance. Although it is more common in North America and Western Europe, its incidence is also increasing in Asia. Despite the introduction of several different classes of medications, the treatment options for UC may be insufficiently effective and burdened with significant side effects. In the present study, the therapeutic effects of Gancao Xiexin decoction (GCXX) were investigated on mice with dextran sulfate sodium (DSS)-induced colitis with exploration of the underlying mechanisms. Methods: Colitis was induced in C57BL/6 mice by administering 3% DSS in drinking water for 7 days. GCXX and (or) the standard of care anti-inflammatory drug, mesalazine (5-aminosalicylic acid) were then administered for 7 days. The gut microbiota was characterized by 16S rDNA high-throughput gene sequencing and gut metabolites were detected by untargeted metabolomics. Germ-free mice were subsequently used to determine whether GCXX ameliorated UC principally through modulation of the gut microbiota. Results: GCXX treatment was demonstrated to significantly reduce disease activity index (DAI) scores, prevent colonic shortening, ameliorate colonic tissue damage and reduce the levels of pro-inflammatory cytokines. Furthermore, analysis of the gut microbiota showed that GCXX-treated mice had higher relative quantity of Dubosiella (P<0.05) and lower relative quantity of Escherichia-Shigella (P<0.05). Metabolomics analysis indicated that GCXX could reduce the level of linoleic acid (P<0.05) and regulate its metabolism pathway. Moreover, in germ-free mice, GCXX failed to increase body weight, reduce DAI scores, or alleviate either colonic shortening or colonic damage. Conclusion: The present study demonstrated that GCXX ameliorated DSS-induced colitis principally through modulating the gut microbiota and metabolites. This information should be integrated into the overall mechanisms of GCXX treatment of UC.

Early gut microbiota in very low and extremely low birth weight preterm infants with feeding intolerance: a prospective case-control study.

The potential role of the gut microbiota in the pathogenesis of feeding intolerance (FI) remains unclear. Understanding the role of the gut microbiota could provide a new avenue for microbiota-targeted therapeutics. This study aimed to explore the associations between aberrant gut microbiota and FI in very low or extremely low birth weight (VLBW/ELBW) preterm infants. In this observational case-control study, VLBW/ELBW infants were divided into two groups: FI group and feeding tolerance (FT) group. 16S rRNA gene sequencing was performed to analyze the gut microbial diversity and composition of the infants. The differences in the gut microbiota of the two groups were compared. In total, 165 stool samples were obtained from 44 infants, among which, 31 developed FI and 13 served as controls. Alpha diversity was the highest in the meconium samples of the two groups. LEfSe analysis revealed that the abundances of Peptostreptococcaceae, Clostridiales and Clostridia in the FT group were significantly higher than in the FI group. At the phylum level, the FI group was dominated by Proteobacteria, and the FT group was dominated by Firmicutes. The meconium samples of the FI group had higher proportions of γ-proteobacteria and Escherichia-Shigella and a lower proportion of Bacteroides compared with the FT group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that aberrant gut bacteria in the FI group were strongly associated with dysregulation of C5-Branched-dibasic-acid-metabolism, protein kinases, and sporulation. These findings reveal candidate microbial markers to prevent FI. Increased relative abundances of γ-proteobacteria and Escherichia-Shigella and decreased abundance of Bacteroides in meconium were associated with an increased risk of FI, while Peptostreptococcaceae, Clostridiales and Clostridia reduced the risk of FI in VLBW/ELBW infants.

Commensal cow Roseburia reduces gut-dysbiosis-induced mastitis through inhibiting bacterial translocation by producing butyrate in mice.

The precise mechanism by which gut dysbiosis contributes to the pathogenesis of extraintestinal diseases and how commensal microbes mediate these processes remain unclear. Here, we show that cows with mastitis had marked gut dysbiosis, characterized by the enrichment of opportunistic pathogenic Escherichia_Shigella and the depletion of commensal Roseburia. Fecal microbiota transplantation from donor cows with mastitis (M-FMT) to recipient mice significantly caused mastitis and changed the gut and mammary microbiota in mice. Notably, M-FMT facilitated the translocation of pathobiont from the gut into the mammary gland, and the depletion of Enterobacteriaceae alleviated M-FMT-induced mastitis in mice. In contrast, commensal Roseburia intestinalis improved M-FMT-induced mastitis and microbial dysbiosis in the gut and mammary gland and limited bacterial translocation by producing butyrate, which was associated with inflammatory signaling inhibition and barrier repair. Our research suggests that commensal Roseburia alleviates gut-dysbiosis-induced mastitis, although further studies in dairy cows and humans are needed.

Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation.

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity; depleting Escherichia-Shigella and the Enterobacteriaceae family; and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut-kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.