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.

Identification of a protective Bacteroides strain of alcoholic liver disease and its synergistic effect with pectin.

The depletion of Bacteroides in the gut is closely correlated with the progression of alcoholic liver disease (ALD). This study aimed to identify Bacteroides strains with protective effects against ALD and evaluate the synergistic effects of Bacteroides and pectin in this disease. Mice were fed Lieber-DeCarli alcohol diet to establish an experimental ALD model and pre-treated with 4 Bacteroides strains. The severity of the liver injury, hepatic steatosis, and inflammation was evaluated through histological and biochemical assays. We found that Bacteroides fragilis ATCC25285 had the best protective effects against ALD strains by alleviating both ethanol-induced liver injury and steatosis. B. fragilis ATCC25285 could counteract inflammatory reactions in ALD by producing short-chain fat acids (SCFAs) and enhancing the intestinal barrier. In the subsequent experiment, the synbiotic combination of B. fragilis ATCC25285 and pectin was evaluated and the underlying mechanisms were investigated by metabolomic and microbiome analyses. The combination elicited superior anti-ALD effects than the individual agents used alone. The synergistic effects of B. fragilis ATCC25285 and pectin were driven by modulating gut microbiota, improving tryptophan metabolism, and regulating intestinal immune function. Based on our findings, the combination of B. fragilis ATCC25285 and pectin can be considered a potential treatment for ALD. KEY POINTS: • B. fragilis ATCC25285 was identified as a protective Bacteroides strain against ALD. • The synbiotic combination of B. fragilis and pectin has better anti-ALD effects. • The synbiotic combination modulates gut microbiota and tryptophan metabolism.

Pediococcus pentosaceus, a future additive or probiotic candidate.

BACKGROUND: Pediococcus pentosaceus, a promising strain of lactic acid bacteria (LAB), is gradually attracting attention, leading to a rapid increase in experimental research. Due to increased demand for practical applications of microbes, the functional and harmless P. pentosaceus might be a worthwhile LAB strain for both the food industry and biological applications. RESULTS: As an additive, P. pentosaceus improves the taste and nutrition of food, as well as the storage of animal products. Moreover, the antimicrobial abilities of Pediococcus strains are being highlighted. Evidence suggests that bacteriocins or bacteriocin-like substances (BLISs) produced by P. pentosaceus play effective antibacterial roles in the microbial ecosystem. In addition, various strains of P. pentosaceus have been highlighted for probiotic use due to their anti-inflammation, anticancer, antioxidant, detoxification, and lipid-lowering abilities. CONCLUSIONS: Therefore, it is necessary to continue studying P. pentosaceus for further use. Thorough study of several P. pentosaceus strains should clarify the benefits and drawbacks in the future.

Modulation of the immune response and metabolism in germ-free rats colonized by the probiotic Lactobacillus salivarius LI01.

The gut microbiota plays an important role in multifaceted physiological functions in the host. Previous studies have assessed the probiotic effects of Lactobacillus salivarius LI01. In this study, we aimed to investigate the potential effects and putative mechanism of L. salivarius LI01 in immune modulation and metabolic regulation through the monocolonization of germ-free (GF) Sprague-Dawley (SD) rats with L. salivarius LI01. The GF rats were separated into two groups and administered a gavage of L. salivarius LI01 or an equal amount of phosphate-buffered saline. The levels of serum biomarkers, such as interleukin (IL)-1α, IL-5, and IL-10, were restored by L. salivarius LI01, which indicated the activation of Th0 cell differentiation toward immune homeostasis. L. salivarius LI01 also stimulated the immune response and metabolic process by altering transcriptional expression in the ileum and liver. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which indicated that L. salivarius LI01 exerts an effect on energy accumulation. The LI01 group showed alterations in fecal carbohydrates accompanied by an increased body weight gain. In addition, L. salivarius LI01 produced indole-3-lactic acid (ILA) and enhanced arginine metabolism by rebalancing the interconversion between arginine and proline. These findings provide evidence showing that L. salivarius LI01 can directly impact the host by modulating immunity and metabolism. KEY POINTS : • Lactobacillus salivarius LI01 conventionalizes the cytokine profile and activates the immune response. • LI01 modulates carbohydrate metabolism and arginine transaction. • LI01 generates tryptophan-derived indole-3-lactic acid. • The cytochrome P450 family contributes to the response to altered metabolites.

Clinical Characteristics and Factors Associated With Long-Term Viral Excretion in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Single-Center 28-Day Study.

BACKGROUND: Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited. METHODS: In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding. RESULTS: Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12-19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35-.98]), immunoglobulin use (HR, 0.42 [95% CI, .24-.76]), APACHE II score (HR, 0.89 [95% CI, .84-.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05-3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. CONCLUSIONS: SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.

Enzymatic Tailoring in Luzopeptin Biosynthesis Involves Cytochrome†P450-Mediated Carbon-Nitrogen Bond Desaturation for Hydrazone Formation.

Luzopeptins and related decadepsipeptides are bisintercalator nonribosomal peptides featuring rare acyl-substituted tetrahydropyridazine-3-carboxylic acid (Thp) subunits that are critical to their biological activities. Herein, we reconstitute the biosynthetic tailoring pathway in luzopeptin A biosynthesis through in vivo genetic and in vitro biochemical approaches. Significantly, we revealed a multitasking cytochrome P450 enzyme that catalyzes four consecutive oxidations including the highly unusual carbon-nitrogen bond desaturation, forming the hydrazone-bearing 4-OH-Thp residues. Moreover, we identified a membrane-bound acyltransferase that likely mediates the subsequent O-acetylation extracellularly, as a potential self-protective strategy for the producer strain. Further genome mining of novel decadepsipeptides and an associated P450 enzyme have provided mechanistic insights into the P450-mediated carbon-nitrogen bond desaturation. Our results not only reveal the molecular basis of pharmacophore formation in bisintercalator decadepsipeptides, but also expand the catalytic versatility of P450 family enzymes.

Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS: We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing. RESULTS: Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). CONCLUSIONS: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

Characteristics of the urinary microbiome in kidney stone patients with hypertension.

BACKGROUND: Kidney stone disease (KSD) is more common in individuals with hypertension (HTN) than in individuals with normotension (NTN). Urinary dysbiosis is associated with urinary tract disease and systemic diseases. However, the role of the urinary microbiome in KSD complicated with HTN remains unclear. METHODS: This study investigated the relationship between the pelvis urinary microbiome and blood pressure (BP) in patients with KSD co-occurring with HTN (KSD-HTN) and healthy controls (HC) by conducting 16S rRNA gene sequencing of bacteria in urine samples. The urine samples were collected (after bladder disinfection) from 50 patients with unilateral kidney calcium stones and NTN (n = 12), prehypertension (pHTN; n = 11), or HTN (n = 27), along with 12 HCs. RESULTS: Principal coordinates analysis showed that there were significant differences in the urinary microbiomes not only between KSD patients and HCs but also between KSD-pHTN or KSD-HTN patients and KSD-NTN patients. Gardnerella dominated in HCs, Staphylococcus dominated in KSD-NTN patients and Sphingomonas dominated in both KSD-pHTN and KSD-HTN patients. The abundance of several genera including Acidovorax, Gardnerella and Lactobacillus was correlated with BP. Adherens junction and nitrogen and nucleotide metabolism pathways, among others, were associated with changes in BP. CONCLUSIONS: The findings suggest that patients with KSD complicated with HTN have a unique urinary microbiome profile and that changes in the microbiome may reflect disease progression and may be useful to monitor response to treatments.

Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer.

BACKGROUND: The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking. RESULTS: We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1 M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation. CONCLUSIONS: Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC.

The fiber metabolite butyrate reduces gp130 by targeting TRAF5 in colorectal cancer cells.

BACKGROUND: Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug. METHODS: In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro. RESULTS: Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5. CONCLUSIONS: The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.

Lactobacillus salivarius LI01 encapsulated in alginate-pectin microgels ameliorates D-galactosamine-induced acute liver injury in rats.

Acute liver failure is a clinical emergency associated with high mortality. Accumulating evidence indicates that gut microbiota participates in the progression of liver injury, and preventive therapies based on altering gut microbiota are of great interest. Previous studies demonstrated that Lactobacillus salivarius LI01 attenuates hepatic injury, though efficiency in curtailed in the harsh environment in the gastrointestinal tract. In this study, a system to encapsulate LI01 in alginate-pectin (AP) microgels was investigated. Encapsulation significantly enhances probiotic viability for long-term storage and heat treatment, and in simulated gastrointestinal fluids (SGF or SIF) and bile salt solutions. Acute liver injury was induced in Sprague-Dawley (SD) rats by D-galactosamine (D-GaIN) injection following pretreatment with probiotics. Liver and gut barrier function, cytokines, liver and gut histology, bacterial translocation, and gut microbiota were assessed. Administration of encapsulated LI01 more effectively upregulates hepatic anti-inflammatory cytokine IL-10 and TLR-3, restores expressions of gut barrier biomarkers Claudin-1 and MUC2 and attenuates destruction of mucosal ultrastructure compared with unencapsulated probiotics pretreatment. Pretreatment with AP-LI01 microgels altered the microbial community, decreasing the abundance of pathogenic taxa Ruminiclostridium, Dorea and Ruminococcaceae_UCG-004 and enriching beneficial taxa Ruminococcaceae_UCG-014, Eubacterium, and Prevotella_1 that produce short-chain fatty acids. These results suggest that AP encapsulation of LI01 boosts viability and attenuates liver injury by reducing inflammation and restoring intestinal barrier function. These beneficial effects are probably due to alternation of gut flora. These findings provide new insight into encapsulation technology and prevention of liver failure. KEY POINTS: • Alginate-pectin encapsulation enhances the viability of Lactobacillus salivarius LI01 under simulated commercial conditions and simulated gastrointestinal environment. • AP-LI01 microgel attenuates hepatic and intestinal inflammation and restores gut barrier function. • AP-LI01 microgel alters gut microbial community with increased SCFAs producers and decreased pathogenic microbes. • Beneficial improvements after administration of probiotics are highly associated with alternation of gut microbial community.

Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice.

The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 109 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.

TCRß repertoire of memory T cell reveals potential role for Escherichia coli in the pathogenesis of primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is an organ-specific, T cell-mediated autoimmune disease which is characterized by the breakdown of self-tolerance to the highly conserved pyruvate dehydrogenase complex, especially the pyruvate dehydrogenase E2 complex (PDC-E2). However, the molecular mechanism of breakdown of self-tolerance is still unclear. METHODS: A combination of multiplex-PCR and immune repertoire sequencing (IR-seq) was used for a standardized analysis of memory T cell receptor (TCR) ß-chain repertoire of PBC patient and healthy volunteers. In vitro induction and expansion of human PDC-E2163-176 (human PDC-E2)-specific T cells and E coli PDC-E231-44/134-147/235-248 (E coli PDC-E2)-specific T cells, and identified the human (and E coli) PDC-E2-specific TCRß repertoire by IR-seq. RESULTS: Primary biliary cholangitis patients have shorter complementarity-determining region 3s (CDR3s), and higher degree of sequence overlap in the TCRß repertoire of memory T cell. Moreover, altered insertion patterns and skewed TRBV segment usage were observed in PBC patients. With regard to the pathogenesis, the concentration of E coli was higher in PBC patients' faecal. The frequency of E coli (and human)-specific TCRs was higher in the memory TCRß repertoire of PBC patients compared with healthy controls. Importantly, the TCRß repertoire characteristics were almost identical between E coli PDC-E2-related TCRs and human PDC-E2-related TCRs, including the patterns of TRBV usage, CDR3 length and amino acid composition. CONCLUSION: Our findings comprehensively revealed the TCRß repertoire characterization of PBC patients, and provided a TCR molecular basis to understand the mechanism of cross-recognition between human PDC-E2 and E coli PDC-E2, and the imbalance of immune tolerance in PBC.

Bifidobacterium adolescentis CGMCC 15058 alleviates liver injury, enhances the intestinal barrier and modifies the gut microbiota in D-galactosamine-treated rats.

Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 109 CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days. Acute liver injury was induced on the 15th day by intraperitoneal injection of D-galactosamine. After 24 h, liver and terminal ileum histology, liver function, plasma cytokines, bacterial translocation and gut microbiota composition were assessed. We found that pretreatment with B. adolescentis significantly relieved elevated serum levels of alanine aminotransferase (ALT), total bile acid and lipopolysaccharide-binding protein and enhanced the expression of mucin 4 and the tight junction protein zonula occludens-1. B. adolescentis exhibited anti-inflammatory properties as indicated by decreased levels of mTOR and the inflammatory cytokines TNF-α and IL-6, as well as elevated levels of the anti-inflammatory cytokine interleukins-10 in the liver. Similar anti-inflammatory signs were also found in plasma. B. adolescentis significantly altered the microbial community, depleting the common pathogenic taxon Proteus and markedly enriching the taxa Coriobacteriaceae, Bacteroidales and Allobaculum, which are involved in regulating the metabolism of lipids and aromatic amino acids. Our findings not only suggest B. adolescentis acts as a prospective probiotic against liver failure but also provide new insights into the prevention and treatment of liver disease.

Lactobacillus helveticus R0052 alleviates liver injury by modulating gut microbiome and metabolome in D-galactosamine-treated rats.

The liver is an important digestive gland, and acute liver failure results in high mortality. Probiotics are considered potential adjuvant therapies for liver disease. This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052 on acute liver injury and the underlying mechanisms. Sprague-Dawley rats were gavaged with L. helveticus R0052 suspensions (3 × 109 CFU) for 1 week. Subsequently, acute liver injury was induced by intraperitoneal D-galactosamine injection on the eighth day. After 24 h, samples (blood, liver, ileum, faeces) were collected and assessed for histological injury, inflammation, intestinal barrier, gut microbiome and metabolome. L. helveticus R0052 alleviated aminotransferase, bilirubin and total bile acid elevation and histological hepatic injuries. Additionally, L. helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors, tumour necrosis factor-α and nuclear factor-κb transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations. Additionally, L. helveticus R0052 ameliorated intestinal abnormalities and regulated Toll-like receptors, claudin2 and mucin3 gene transcription in the intestine. These effects were associated with gut microbiome and metabolome modulation by L. helveticus R0052. Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels. These results indicate that L. helveticus R0052 is promising for alleviating acute liver injury and provide new insights regarding the correlations among the microbiome, the metabolome, the intestinal barrier and liver disease.

Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis.

We selected 42 early-stage primary biliary cirrhosis (PBC) patients and 30 healthy controls (HC). Metagenomic sequencing of the 16S rRNA gene was used to characterize the fecal microbiome. UPLC-MS/MS assaying of small molecules was used to characterize the metabolomes of the serum, urine and feces. Liquid chip assaying of serum cytokines was used to characterize the immune profiles. The gut of PBC patients were depleted of some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii and Ruminococcus bromii, but were enriched in some bacterial taxa containing opportunistic pathogens, such as γ-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara. Several altered gut bacterial taxa exhibited potential interactions with PBC through their associations with altered metabolism, immunity and liver function indicators, such as those of Klebsiella with IL-2A and Neisseriaceae with urinary indoleacrylate. Many gut bacteria, such as some members of Bacteroides, were altered in their associations with the immunity and metabolism of PBC patients, although their relative abundances were unchanged. Consequently, the gut microbiome is altered and may be critical for the onset or development of PBC by interacting with metabolism and immunity.

Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05 improves acute liver injury induced by D-galactosamine in rats.

This work investigated the effect of the intragastric administration of five lactic acid bacteria from healthy people on acute liver failure in rats. Sprague-Dawley rats were given intragastric supplements of Lactobacillus salivarius LI01, Lactobacillus salivarius LI02, Lactobacillus paracasei LI03, Lactobacillus plantarum LI04, or Pediococcus pentosaceus LI05 for 8 days. Acute liver injury was induced on the eighth day by intraperitoneal injection of 1.1 g/kg body weight D-galactosamine (D-GalN). After 24 h, samples were collected to determine the level of liver enzymes, liver function, histology of the terminal ileum and liver, serum levels of inflammatory cytokines, bacterial translocation, and composition of the gut microbiome. The results indicated that pretreatment with L. salivarius LI01 or P. pentosaceus LI05 significantly reduced elevated alanine aminotransferase and aspartate aminotransferase levels, prevented the increase in total bilirubin, reduced the histological abnormalities of both the liver and the terminal ileum, decreased bacterial translocation, increased the serum level of interleukin 10 and/or interferon-γ, and resulted in a cecal microbiome that differed from that of the liver injury control. Pretreatment with L. plantarum LI04 or L. salivarius LI02 demonstrated no significant effects during this process, and pretreatment with L. paracasei LI03 aggravated liver injury. To the best of our knowledge, the effects of the three species-L. paracasei, L. salivarius, and P. pentosaceus-on D-GalN-induced liver injury have not been previously studied. The excellent characteristics of L. salivarius LI01 and P. pentosaceus LI05 enable them to serve as potential probiotics in the prevention or treatment of acute liver failure.