Demographics and prognosis of patients with pyogenic liver abscess due to Klebsiella pneumonia or other species.

Background: Pyogenic liver abscess (PLA) is a potentially life-threatening intra-abdominal infection. We compared the clinical features, treatments, and prognoses of patients who had Klebsiella pneumonia pyogenic liver abscess (KPPLA) and non-Klebsiella pneumonia pyogenic liver abscess (non-KPPLA). Methods: A retrospective analysis was used to compare the medical records of KPPLA and non-KPPLA patients with positive pus cultures at a single hospital in China from January 2017 to December 2019. Results: We examined 279 patients with definitively established PLA, 207 (74.2 %) with KPPLA, and 72 with non-KPPLA. The non-KPPLA group had a higher Charlson comorbidity index, longer hospital stay, longer duration of fever, and greater hospital costs. Multivariate analysis showed that alcohol intake (OR: 2.44, P = 0.048), cancer (OR: 4.80, P = 0.001), ICU admission (OR: 10.61, P = 0.026), resolution of fever OR: 1.04, P = 0.020), and a positive blood culture (OR: 2.87, P = 0.029) were independent predictors of primary treatment failure. Percutaneous needle aspiration (PNA) and pigtail catheter drainage (PCD) provided satisfactory outcomes, but PNA led to shorter hospital stays and reduced costs, especially in KPPLA patients whose abscesses were smaller than 10 cm. Conclusion: KPPLA and non-KPPLA patients had some differences in comorbidities and treatment strategies, and non-KPPLA patients had a significantly worse prognosis.

Close contact behaviors of university and school students in 10 indoor environments.

Close contact routes, including short-range airborne and large-droplet routes, play an important role in the transmission of SARS-CoV-2 in indoor environments. However, the exposure risk of such routes is difficult to quantify due to the lack of data on the close contact behavior of individuals. In this study, a digital wearable device, based on semi-supervised learning, was developed to automatically record human close contact behavior. We collected 337,056 s of indoor close contact of school and university students from 194.5 h of depth video recordings in 10 types of indoor environments. The correlation between aerosol exposure and close contact behaviors was then evaluated. Individuals in restaurants had the highest close contact ratio (64%), as well as the highest probability of face-to-face pattern (78%) during close contact. Accordingly, university students showed greater exposure potential in dormitories than school students in homes, however, a lower exposure was observed in classrooms and postgraduate student offices in comparison with school students in classrooms. In addition, restaurants had the highest aerosol exposure volume for both short-range inhalation and direct deposition on the facial mucosa. Thus, the classroom was established as the primary indoor environment where school students are exposed to aerosols.

Short- and Long-Term Effects of Different Antibiotics on the Gut Microbiota and Cytokines Level in Mice.

Background: Antibiotics are the first line of treatment for infectious diseases. However, their overuse can increase the spread of drug-resistant bacteria. The present study analyzed the impact of different types of antibiotics on the gut microbiome and cytokines level of mice. Methods: A total of five groups of 8-week-old male BALB/c mice (n = 35) were treated with piperacillin-tazobactam (TZP), ceftriaxone (CRO), tigecycline (TGC), levofloxacin (LEV) or normal saline (Ctrl), respectively, for up to 4 weeks. Fecal samples were analyzed by bacterial 16S rRNA gene sequencing for bacterial identification. Blood samples were used for the determination of 23 serum cytokines using multiplex immunoassay. Results: Exposure to antibiotics was shown to affect the normal weight gain of mice. Significant changes in gut composition caused by TZP, CRO and TGC treatment included the decreased abundance of Bacteroidetes (p < 0.01), Muribaculaceae (p < 0.01) and Lachnospiraceae (p < 0.01), and the increased abundance of Proteobacteria (p < 0.05), Enterobacteriaceae (including Klebsiella and Enterobacter) (p < 0.01) and Enterococcaceae (including Enterococcus) (p < 0.01). After 4-week treatment, the TZP, CRO and LEV groups had significantly lower concentrations of several serum cytokines. Correlation analysis of the top 30 bacterial genera and cytokines showed that Enterococcus and Klebsiella were strongly positively correlated with tumor necrosis factor-α (TNF-α), interleukins (IL) IL-12p70 and IL-1ß. Desulfovibrio, Candidatus Saccharimonas, norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, and Roseburia were strongly negatively correlated with these cytokines. Conclusion: This study demonstrates the effects of various antibiotics on the intestinal microflora and immune status of mice. Compared with TZP, CRO and TGC, LEV had minimal impact on the gut microbiota. In addition to TGC, long-term TZP, CRO and LEV intervention can lead to a decrease in serum cytokine levels, which may depend on the intestinal microflora, antibiotic used and the duration of treatment.

The evaluation of fecal microbiota transplantation vs vancomycin in a Clostridioides difficile infection model.

Vancomycin is the preferred treatment for Clostridioides difficile infection (CDI) but has been associated with a high recurrence rate of CDI in treated patients. Fecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent CDI (rCDI). Herein, we present a mouse model of CDI to further define the changes in intestinal inflammation, flora, and metabolites following FMT versus vancomycin treatment and to find the potential therapy to restore colonization resistance. Both FMT and vancomycin treatment could ameliorate CDI-induced clinical features and intestinal tissue damage, with decrease in the levels of inflammatory mediators like IL-1ß, IL-6, TNF-α, G-CSF, and MCP-1 in the colon and plasma. Observing the fecal gut microbiome profile revealed that unlike vancomycin, FMT could replenish intestinal microbiota by augmenting the relative abundance of the phylum Bacteroidetes and eliminating the abundance of the phylum Proteobacteria. FMT also reduced the levels of several carbohydrates, such as raffinose and fructose-6-phosphate, and amino acids, including tryptophan and glutamyl-valine, in the gut metabolome, thus suppressing C. difficile germination and growth. Our results suggest that the FMT-induced reconstruction of a specific gut community structure and restoration of metabolites promote the recovery of colonization resistance in mice better than vancomycin, thus offering new insights for the prevention of rCDI. KEY POINTS: • Both FMT and vancomycin ameliorate CDI-induced inflammatory response. • FMT restores a specific community structure and gut metabolites. • Mice treated with FMT may promote the recovery of colonization resistance and has a better outcome.

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites.

Clostridioides difficile is a common cause of nosocomial infection. Antibiotic-induced dysbiosis in the intestinal microbiota is a core cause of C. difficile infection (CDI). Akkermansia muciniphila plays an active role in maintaining gastrointestinal balance and might offer the protective effects on CDI as probiotics. Here, we investigated the effects and mechanisms of A. muciniphila on CDI. C57BL/6 mice (n = 29) were administered A. muciniphila Muc T (3 × 109 CFUs, 0.2 mL) or phosphate-buffered saline (PBS) by oral gavage for 2 weeks. Mice were pretreated with an antibiotic cocktail and subsequently challenged with the C. difficile strain VPI 10463. A. muciniphila treatment prevented weight loss in mice and reduced the histological injury of the colon. And it also alleviated inflammation and improved the barrier function of the intestine. The administration effects of A. muciniphila may be associated with an increase in short-chain fatty acid production and the maintenance of bile acids' steady-state. Our results provide evidence that administration of A. muciniphila to CDI mice, with an imbalance in the microbial community structure, lead to a decrease in abundance of members of the Enterobacteriaceae and Enterococcaceae. In short, A. muciniphila shows a potential anti-CDI role by modulating gut microbiota and the metabolome.

Modulation of Lactobacillus rhamnosus GG on the gut microbiota and metabolism in mice with Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a common nosocomial infection and is an urgent threat to public health. Vancomycin is the preferred antibiotic treatment for CDI but is associated with recurrence. Lactobacillus rhamnosus GG is an adjunctive treatment for gastroenteritis and diarrhea and exerts its effects by modulating the immune responses and repairing the intestinal barrier. This study explored the effect of LGG on restoring the intestinal microbiota in mouse models. Primary and recurrent CDI models were constructed, and LGG was administered to C57BL/6 mice. Structural changes in the mouse gut microbiota were determined using 16S rRNA gene analysis based on Illumina sequencing. In the CDI model, 6 days after infection, 33.3% mortality, significant weight loss and colonic injury were observed. LGG can ameliorate these events. In the R-CDI mouse model, vancomycin combined with LGG prevented weight loss, improved the histopathological scores, and effectively reduced the mortality. LGG + vancomycin administration promoted the recovery of the intestinal flora by inhibiting Enterococcus and counteracting the side effects of vancomycin treatment. In both the preventive and therapeutic CDI mouse models, the oral LGG strain showed the ability to protect against primary and recurrent infections, indicating that probiotics have potential for treating intestinal diseases. Overall, these observations suggest that LGG can be applied as a preventive treatment for CDI or in combination with antibiotics to reduce recurrence.

Disordered Intestinal Microbial Communities During Clostridioides difficile Colonization and Subsequent Infection of Hepatic Cirrhosis Patients in a Tertiary Care Hospital in China.

Patients with hepatic cirrhosis are more susceptible to Clostridioides difficile infection (CDI) and colonization with Clostridioides difficile (C. difficile). Asymptomatic C. difficile colonization is thought to predispose to subsequent CDI. However, the dynamic gut microbiota changes remain unclear. In this study, we used 16S rRNA gene sequencing to longitudinally monitor alterations in the intestinal microbiota of 22 hepatic cirrhosis patients with toxigenic C. difficile colonization at admission (pre-CDI) and developed CDI during hospitalization, subdivided into pre-CDI and CDI. 21 hospitalized cirrhotic patients without C. difficile colonization served as controls (HC). Compared with HC, pre-CDI and CDI samples had significantly decreased microbial richness and diversity, a significantly higher relative abundance of opportunistic pathogen Enterococcus, and a lower relative abundance of beneficial symbionts, such as Faecalibacterium, Dorea, and Roseburia. Three biomarkers showed high accuracy for distinguishing pre-CDI samples from HC with an area under the curve (AUC) up to 0.81. In conclusion, our study explored the changes of the gut microbiome before and after CDI. The gut microbial richness as well as diversity in CDI patients were notably reduced, relative to controls. Imbalance of the intestinal flora may be related to the risk for development of CDI. Identifying key members of the gut microbiota and illustrating their roles and mechanisms of action in CDI development are important avenues for future research.

A comparison of demographic, epidemiological and clinical characteristics of hospital influenza-related viral pneumonia patients.

BACKGROUND: Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them. METHODS: A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients. RESULTS: Human influenza A-related patients in the 35-49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54-121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48-24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06-84.07; p = 0.006), white blood cell count > 10,000/mm3 (OR: 7.22; 95% CI 1.47-35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36-28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients. CONCLUSIONS: Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm3, and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients.

The Salivary Microbiota of Patients With Primary Biliary Cholangitis Is Distinctive and Pathogenic.

The role of host-microbiota interactions in primary biliary cholangitis (PBC) has received increased attention. However, the impact of PBC on the oral microbiota and contribution of the oral microbiota to PBC are unclear. In this study, thirty-nine PBC patients without other diseases and 37 healthy controls (HCs) were enrolled and tested for liver functions and haematological variables. Saliva specimens were collected before and after brushing, microbiota was determined using 16S rDNA sequencing, metabolomics was profiled using Gas Chromatography-Mass Spectrometer (GC-MS), 80 cytokines were assayed using biochips, and inflammation inducibility was evaluated using OKF6 keratinocytes and THP-1 macrophages. Finally, the effect of ultrasonic scaling on PBC was estimated. Compared with HCs, PBC saliva had enriched taxa such as Bacteroidetes, Campylobacter, Prevotella and Veillonella and depleted taxa such as Enterococcaceae, Granulicatella, Rothia and Streptococcus. PBC saliva also had enriched sCD163, enriched metabolites such as 2-aminomalonic acid and 1-dodecanol, and depleted metabolites such as dodecanoic acid and propylene glycol. sCD163, 4-hydroxybenzeneacetic acid and 2-aminomalonic acid were significantly correlated with salivary cytokines, bacteria and metabolites. Salivary Veillonellaceae members, 2-aminomalonic acid, and sCD163 were positively correlated with liver function indicators such as serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PBC salivary microbes induced more soluble interleukin (IL)-6 receptor α (sIL-6Rα), sIL-6Rß and tumour necrosis factor ligand superfamily (TNFSF)13B from OKF6 keratinocytes, and PBC salivary supernatant induced more IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine (C-C motif) ligand (CCL)13, C-X-C motif chemokine (CXC)L1 and CXCL16 from THP-1 macrophages. Toothbrushing significantly reduced the expression of inflammatory cytokines such as IL-1ß, IL-8 and TNF-α and harmful metabolites such as cadaverine and putrescine in PBC but not HC saliva after P-value correction. The levels of ALP and bilirubin in PBC serum were decreased after ultrasonic scaling. Together, PBC patients show significant alterations in their salivary microbiota, likely representing one cause and treatment target of oral inflammation and worsening liver functions.

Gut mycobiota alterations in patients with COVID-19 and H1N1 infections and their associations with clinical features.

The relationship between gut microbes and COVID-19 or H1N1 infections is not fully understood. Here, we compared the gut mycobiota of 67 COVID-19 patients, 35 H1N1-infected patients and 48 healthy controls (HCs) using internal transcribed spacer (ITS) 3-ITS4 sequencing and analysed their associations with clinical features and the bacterial microbiota. Compared to HCs, the fungal burden was higher. Fungal mycobiota dysbiosis in both COVID-19 and H1N1-infected patients was mainly characterized by the depletion of fungi such as Aspergillus and Penicillium, but several fungi, including Candida glabrata, were enriched in H1N1-infected patients. The gut mycobiota profiles in COVID-19 patients with mild and severe symptoms were similar. Hospitalization had no apparent additional effects. In COVID-19 patients, Mucoromycota was positively correlated with Fusicatenibacter, Aspergillus niger was positively correlated with diarrhoea, and Penicillium citrinum was negatively correlated with C-reactive protein (CRP). In H1N1-infected patients, Aspergillus penicilloides was positively correlated with Lachnospiraceae members, Aspergillus was positively correlated with CRP, and Mucoromycota was negatively correlated with procalcitonin. Therefore, gut mycobiota dysbiosis occurs in both COVID-19 patients and H1N1-infected patients and does not improve until the patients are discharged and no longer require medical attention.

Regulatory long non-coding RNAs of hepatic stellate cells in liver fibrosis (Review).

Liver fibrosis (LF) is a continuous wound healing process caused by numerous chronic hepatic diseases and poses a major threat to human health. Activation of hepatic stellate cells (HSCs) is a critical event in the development of hepatic fibrosis. Long non-coding RNAs (lncRNAs) that are involved in HSC activation, participate in the development of LF and are likely to be therapeutic targets for LF. In the present review, the cellular signaling pathways of LF with respect to HSCs were discussed. In particular, this present review highlighted the current knowledge on the role of lncRNAs in activating or inhibiting LF, revealing lncRNAs that are likely to be biomarkers or therapeutic targets for LF. Additional studies should be performed to elucidate the potential of lncRNAs in the diagnosis and prognosis of LF and to provide novel therapeutic approaches for the reversion of LF.

The serum metabolome of COVID-19 patients is distinctive and predictive.

BACKGROUND: Metabolism is critical for sustaining life, immunity and infection, but its role in COVID-19 is not fully understood. METHODS: Seventy-nine COVID-19 patients, 78 healthy controls (HCs) and 30 COVID-19-like patients were recruited in a prospective cohort study. Samples were collected from COVID-19 patients with mild or severe symptoms on admission, patients who progressed from mild to severe symptoms, and patients who were followed from hospital admission to discharge. The metabolome was assayed using gas chromatography-mass spectrometry. RESULTS: Serum butyric acid, 2-hydroxybutyric acid, l-glutamic acid, l-phenylalanine, l-serine, l-lactic acid, and cholesterol were enriched in COVID-19 and COVID-19-like patients versus HCs. Notably, d-fructose and succinic acid were enriched, and citric acid and 2-palmitoyl-glycerol were depleted in COVID-19 patients compared to COVID-19-like patients and HCs, and these four metabolites were not differentially distributed in non-COVID-19 groups. COVID-19 patients had enriched 4-deoxythreonic acid and depleted 1,5-anhydroglucitol compared to HCs and enriched oxalic acid and depleted phosphoric acid compared to COVID-19-like patients. A combination of d-fructose, citric acid and 2-palmitoyl-glycerol distinguished COVID-19 patients from HCs and COVID-19-like patients, with an area under the curve (AUC) > 0.92 after validation. The combination of 2-hydroxy-3-methylbutyric acid, 3-hydroxybutyric acid, cholesterol, succinic acid, L-ornithine, oleic acid and palmitelaidic acid predicted patients who progressed from mild to severe COVID-19, with an AUC of 0.969. After discharge, nearly one-third of metabolites were recovered in COVID-19 patients. CONCLUSIONS: The serum metabolome of COVID-19 patients is distinctive and has important value in investigating pathogenesis, determining a diagnosis, predicting severe cases, and improving treatment.

The faecal metabolome in COVID-19 patients is altered and associated with clinical features and gut microbes.

Although SARS-CoV-2 can invade the intestine, though its effect on digestion and absorption is not fully understood. In the present study, 56 COVID-19 patients and 47 age- and sex-matched healthy subjects were divided into a discovery cohort and a validation cohort. Blood, faeces and clinical information were collected from the patients in the hospital and at discharge. The faecal metabolome was analysed using gas chromatography-mass spectrometry, and Spearman's correlation analyses of clinical features, the serum metabolome, and the faecal micro- and mycobiota were conducted. The results showed that, the faeces of COVID-19 patients were enriched with important nutrients that should be metabolized or absorbed, such as sucrose and 2-palmitoyl-glycerol; diet-related components that cannot be synthesized by humans, such as 1,5-anhydroglucitol and D-pinitol; and harmful metabolites, such as oxalate, were also detected. In contrast, purine metabolites such as deoxyinosine and hypoxanthine, low-water-soluble long-chain fatty alcohols/acids such as behenic acid, compounds rarely occurring in nature such as D-allose and D-arabinose, and microbe-related compounds such as 2,4-di-tert-butylphenol were depleted in the faeces of COVID-19 patients. Moreover, these metabolites significantly correlated with altered serum metabolites such as oxalate and gut microbesincluding Ruminococcaceae, Actinomyces, Sphingomonas and Aspergillus. Although levels of several faecal metabolites, such as sucrose, 1,5-anhydroglucitol and D-pinitol, of discharged patients were not different from those of healthy controls (HCs), those of oxalate and 2-palmitoyl-glycerol did differ. Therefore, alterations in the faecal metabolome of COVID-19 patients may reflect malnutrition and intestinal inflammation and warrant greater attention. The results of present study provide new insights into the pathogenesis and treatment of COVID-19.

Multi-route transmission potential of SARS-CoV-2 in healthcare facilities.

Understanding the transmission mechanism of SARS-CoV-2 is a prerequisite to effective control measures. To investigate the potential modes of SARS-CoV-2 transmission, 21 COVID-19 patients from 12-47 days after symptom onset were recruited. We monitored the release of SARS-CoV-2 from the patients' exhaled breath and systematically investigated environmental contamination of air, public surfaces, personal necessities, and the drainage system. SARS-CoV-2 RNA was detected in 0 of 9 exhaled breath samples, 2 of 8 exhaled breath condensate samples, 1 of 12 bedside air samples, 4 of 132 samples from private surfaces, 0 of 70 samples from frequently touched public surfaces in isolation rooms, and 7 of 23 feces-related air/surface/water samples. The maximum viral RNA concentrations were 1857 copies/m3 in the air, 38 copies/cm2 in sampled surfaces and 3092 copies/mL in sewage/wastewater samples. Our results suggest that nosocomial transmission of SARS-CoV-2 can occur via multiple routes. However, the low detection frequency and limited quantity of viral RNA from the breath and environmental specimens may be related to the reduced viral load of the COVID-19 patients on later days after symptom onset. These findings suggest that the transmission dynamics of SARS-CoV-2 differ from those of SARS-CoV in healthcare settings.

Effect of the Short-Term Use of Fluoroquinolone and ß-Lactam Antibiotics on Mouse Gut Microbiota.

BACKGROUND: Antibiotics play an important role in the treatment of infectious diseases. However, the overuse of antibiotics increases the spread of drug-resistant bacteria and causes dysbiosis of the intestinal microbiota. Few studies have addressed the longitudinal effects of antibiotics on the microbiome and host immunity. MATERIALS AND METHODS: In this study, the short-term effect of fluoroquinolone (levofloxacin) and ß-lactam antibiotics (meropenem, cefoperazone/sulbactam, and aztreonam) on the gut microbiota of mice was evaluated by 16S rRNA gene sequencing. The susceptibility of Bifidobacterium longum, Lactobacillus lactis, Enterococcus faecium, and Clostridium butyricum to these antimicrobial agents was assessed using the disc diffusion method. RESULTS: Our results showed that 4-day antibiotic exposure significantly reduced the alpha and beta diversity of gut bacteria and increased serum inflammatory cytokines, and these changes persisted long after antibiotic withdrawal and did not return to pre-treatment levels. Nonetheless, the bacterial community composition tended to return to pre-treatment levels after discontinuing treatment. The tested probiotic strains were resistant to aztreonam but were sensitive to meropenem and cefoperazone/sulbactam. CONCLUSION: Short-term antibiotic treatment led to significant changes in the intestinal flora with a tendency to recover. The antibiotics had different effects on the intestinal microbial community and probiotic strains. This study provides guidance for the concomitant use of probiotics and antibiotics, and the results emphasize the importance of using broad-spectrum antibiotics responsibly to prevent the long-term disruption of the native microbiota.

Fecal Metabolites Were Altered, Identified as Biomarkers and Correlated With Disease Activity in Patients With Systemic Lupus Erythematosus in a GC-MS-Based Metabolomics Study.

Gut metabolites are products of the crosstalk between microbes and their host and play an important role in the occurrence, development, diagnosis, and treatment of autoimmune diseases. This work profiled the fecal metabolome of patients with systemic lupus erythematosus (SLE) using gas chromatography-mass spectrometry (GC-MS) and analyzed the potential roles of metabolites in the diagnosis and development of SLE. Fecal sample from 29 SLE patients without any other diseases and 30 healthy controls (HCs) were analyzed by metabolomics profiling. All participants took no antibiotics in the month before sampling and clinical data collecting. The metabolome profiles of patients with SLE and HCs were significantly different. Thirty fecal metabolites, such as deoxycholic acid, erucamide, L-tryptophan and putrescine, were significantly enriched, while nine metabolites, such as glyceric acid, γ-tocopherol, (Z)-13-octadecenoic acid and 2,4-di-tert-butylphenol, were depleted in SLE patients vs. HCs. The areas under the curve (AUCs) of L-valine, pyrimidine, erucamide, and L-leucine during ROC analysis were 0.886, 0.833, 0.829, and 0.803, indicating their good diagnostic potential. Moreover, the combination of L-valine, erucamide and 2,4-di-tert-butylphenol gave an AUC of 0.959. SLE-altered metabolites were significantly located in 28 pathways, such as ABC transporters (p = 3.40E-13) and aminoacyl-tRNA biosynthesis (p = 2.11E-12). Furthermore, SLE-altered fecal metabolites were closely correlated with SLE indicators, e.g., L-tryptophan was positively correlated with the SLEDAI-2K (p = 0.007). Our results suggest that the SLE fecal metabolome is closely associated with the occurrence and development of SLE and is of great diagnostic value.

Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia.

Gut microbiota has been implicated in the pathogenesis of many autoimmune diseases. This is still an area of active research given that the role of gut microbiota on the primary immune thrombocytopenia (ITP) remains unclear. In this study, fecal samples of 30 untreated adult primary ITP patients and 29 healthy controls (HCs) were used to investigate the gut microbial community and metabolite profiles. Our results show that fecal bacteria such as Blautia, Streptococcus, and Lactobacillus are enriched, whereas bacteria such as Bacteroides are depleted in ITP patients. Notably, fecal metabolites such as fatty acyls and glycerophospholipids are enriched and strongly correlate with discrepant gut microbiota. Furthermore, combinations of Weissella and Streptococcus anginosus, or Cer (t18:0/16:0), Cer (d18:1/17:0), and 13-hydroxyoctadecanoic acid could provide good diagnostic markers for ITP. Moreover, a strong negative correlation was found between platelet count and altered gut microbiota such as S. anginosus and gut metabolites such as Cer (t18:0/16:0) in ITP. In conclusion, dysbiosis of both gut microbiota and metabolome develops in ITP patients compared to HCs. Several ITP-altered gut bacteria and metabolites can be diagnostic biomarkers for ITP, and are highly correlated with platelet count, suggesting that they may also play a role in ITP pathogenesis.