Research progress on biosynthesis of erythritol and multi-dimensional optimization of production strategies.

Erythritol, as a new type of natural sweetener, has been widely used in food, medical, cosmetics, pharmaceutical and other fields due to its unique physical and chemical properties and physiological functions. In recent years, with the continuous development of strategies such as synthetic biology, metabolic engineering, omics-based systems biology and high-throughput screening technology, people's understanding of the erythritol biosynthesis pathway has gradually deepened, and microbial cell factories with independent modification capabilities have been successfully constructed. In this review, the cheap feedstocks for erythritol synthesis are introduced in detail, the environmental factors affecting the synthesis of erythritol and its regulatory mechanism are described, and the tools and strategies of metabolic engineering involved in erythritol synthesis are summarized. In addition, the study of erythritol derivatives is helpful in expanding its application field. Finally, the challenges that hinder the effective production of erythritol are discussed, which lay a foundation for the green, efficient and sustainable production of erythritol in the future and breaking through the bottleneck of production.

Harnessing Native Bacillus spp. for Sustainable Wheat Production.

The genus Bacillus has been widely applied in contemporary agriculture as an environmentally-friendly biological agent. However, the real effect of commercial Bacillus-based fertilizers and pesticides varies immensely in the field. To harness Bacillus for efficient wheat production, we reviewed the diversity, functionality, and applicability of wheat-associated native Bacillus for the first time. Our main findings are: (i) Bacillus spp. inhabit the rhizosphere, root, stem, leaf, and kernel of wheat; (ii) B. subtilis and B. velezensis are the most widely endophytic species that can be isolated from both below and aboveground tissues; (iii) major functions of these representative strains are promotion of plant growth and alleviation of both abiotic and biotic stresses in wheat; (iv) stability and effectiveness are 2 major challenges during field application; (v) a STVAE pipeline that includes 5 processes, namely, Screen, Test, Validation, Application, and Evaluation, has been proposed for the capture and refinement of wheat-associated Bacillus spp. In particular, this review comprehensively addresses possible solutions, concerns, and criteria during the development of native Bacillus-based inoculants for sustainable wheat production.

Genome-wide identification of PIP5K in wheat and its relationship with anther male sterility induced by high temperature.

BACKGROUND: Phosphatidylinositol 4 phosphate 5-kinase (PIP5K) plays a key enzyme role in the inositol signal transduction system and has essential functions in plants in terms of growth, development, and stress responses. However, systematic studies on the wheat PIP5K gene family and its relation to male sterility have not been reported yet. RESULTS: Sixty-four TaPIP5K genes were identified. The TaPIP5K genes contained similar gene structures and conserved motifs on the same branches of the evolutionary tree, and their cis-regulatory elements were related to MeJA-responsiveness. Furthermore, 49 pairs of collinearity genes were identified and mainly subjected to purification selection during evolution. Synteny analyses showed that some PIP5K genes in wheat and the other four species shared a relatively conserved evolutionary process. The expression levels of many conservative TaPIP5K genes in HT-ms anthers were significantly lower than that in Normal anthers. In addition, HT-ms anthers have no dehiscence, and levels of OPDA and JA-ILE are significantly lower at the trinucleus stage. CONCLUSION: These results indicate that the PIP5K gene family may be associated with male sterility induced by HT, and the reduction of JA-ILE levels and the abnormal levels of these genes expression may be one reason for the HT-ms anthers having no dehiscence, ultimately leading to the abortion of the anthers.

Complete Genome Sequence of Bacillus sp. strain WR11, an Endophyte Isolated from Wheat Root Providing Genomic Insights into Its Plant Growth-Promoting Effects.

Bacillus sp. strain WR11 isolated from the root of wheat (Triticum aestivum L.) possesses abiotic stress alleviating properties and produces several types of enzymes. However, its genomic information is lacking. The study described the complete genome sequence of the bacterium. The size of the genome was 4 202 080 base pairs that consisted of 4 405 genes in total. The G+C content of the circular genome was 43.53% and there were 4 170 coding genes, 114 pseudo genes, 30 ribosome RNAs, 86 tRNAs, and 5 ncRNAs, based on the Prokaryotic Genome Annotation Pipeline (PGAP). Many genes were related to the stress-alleviating properties and 124 genes existed in the CAZy database. The complete genome data of strain WR11 will provide valuable resources for genetic dissection of its plant growth-promoting function and symbiotic interaction with plant.

Using probiotics for type 2 diabetes mellitus intervention: Advances, questions, and potential.

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent diseases on earth and several treatments have been developed. However, the current intervention approaches have not been as effective as expected. One promising supplementary strategy is the use of probiotics through direct or indirect approaches. Probiotics are microbial food cultures conferring health-promoting properties. In this review, we summarized the current theories and mechanisms of T2DM intervention using probiotics and hypothesize that probiotics intervene T2DM during its onsetting, developing, and complicating. For the first time, we comprehensively analyzed T2DM intervention in animal models using both wide-type probiotics in different forms and using recombinant probiotics. Then, probiotic intervention in T2DM patients was reviewed and the main results were compared with that obtained from animal studies. Finally yet importantly, remaining questions that are important such as in which form and in which state, as well as the future potential of probiotic intervention in T2DM were discussed from a perspective of food microbiologists. In conclusion, probiotic intervention in T2DM is promising but there are still many important issues unsolved yet. Critical review of the advances, questions, and potential of probiotic intervention in T2DM promotes the development of this approach for further application in humans.

Solirhodobacter olei gen. nov., sp. nov., a nonphotosynthetic bacterium isolated from oil-contaminated soil.

A nonphotosynthetic, Gram-stain-negative, rod-shaped and motile strain, designated Pet-1T, was isolated from oil-contaminated soil collected from Daqing oil field in China. Optimal growth occurred at 37 °C, pH 5.5 and in 1 % (w/v) NaCl. Q-10 was the sole respiratory quinone. The most abundant fatty acid was C18 : 1É·7c/C18 : 1É·6c (67.4 %). The major polar lipids were phosphatidylglycerol, aminolipid, phosphatidylethanolaine, phosphatidycholine, two unidentified lipids and two unidentified phospholipids. The genomic DNA G+C content was 69.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that Pet-1T shared the highest similarity (95.1 %) to Rhodobacter vinaykumarii DSM 18714T, followed by Sinorhodobacter populi sk2b1T (95.0 %) and Haematobacter massiliensis CCUG 47968T (95.0 %). In the phylogenetic tree, strain Pet-1T formed a separate branch from the closely related genera Rhodobacter, Pararhodobacter, Defluviimonas and Rhodovulum within the family Rhodobacteraceae. Based on the data from the current polyphasic study, it is proposed that the isolate is a novel species of a novel genus within the family Rhodobacteraceae, with the name Solirhodobacter olei gen. nov., sp. nov. The type strain of the type species is Pet-1T (=KCTC 72074T =CCTCC AB 2018368T).

Three-dimensional tumor spheroids for in vitro analysis of bacteria as gene delivery vectors in tumor therapy.

BACKGROUND: Several studies in animal models demonstrated that obligate and facultative anaerobic bacteria of the genera Bifidobacterium, Salmonella, or Clostridium specifically colonize solid tumors. Consequently, these and other bacteria are discussed as live vectors to deliver therapeutic genes to inhibit tumor growth. Therapeutic approaches for cancer treatment using anaerobic bacteria have been investigated in different mouse models. In the present study, solid three-dimensional (3D) multicellular tumor spheroids (MCTS) of the colorectal adenocarcinoma cell line HT-29 were generated and tested for their potential to study prodrug-converting enzyme therapies using bacterial vectors in vitro. RESULTS: HT-29 MCTS resembled solid tumors displaying all relevant features with an outer zone of proliferating cells and hypoxic and apoptotic regions in the core. Upon incubation with HT-29 MCTS, Bifidobacterium bifidum S17 and Salmonella typhimurium YB1 selectively localized, survived and replicated in hypoxic areas inside MCTS. Furthermore, spores of the obligate anaerobe Clostridium sporogenes germinated in these hypoxic areas. To further evaluate the potential of MCTS to investigate therapeutic approaches using bacteria as gene delivery vectors, recombinant bifidobacteria expressing prodrug-converting enzymes were used. Expression of a secreted cytosine deaminase in combination with 5-fluorocytosine had no effect on growth of MCTS due to an intrinsic resistance of HT-29 cells to 5-fluorouracil, i.e. the converted drug. However, a combination of the prodrug CB1954 and a strain expressing a secreted chromate reductase effectively inhibited MCTS growth. CONCLUSIONS: Collectively, the presented results indicate that MCTS are a suitable and reliable model to investigate live bacteria as gene delivery vectors for cancer therapy in vitro.

Antifungal efficacy of Bacillus amyloliquefaciens ZK-9 against Fusarium graminearum and analysis of the potential mechanism of its lipopeptides.

Fusarium graminearum is a destructive fungal pathogen that seriously threatens wheat production and quality. In the management of fungal infections, biological control is an environmentally friendly and sustainable approach. Here, the antagonistic strain ZK-9 with a broad antifungal activity was identified as Bacillus amyloliquefaciens. ZK-9 could produce extracellular enzymes such as pectinase, protease, cellulase, and amylase, as well as plant growth-promoting substances including IAA and siderophore. Lipopeptides extracted from strain ZK-9 had the high inhibitory effects on the mycelia of F. graminearum with the minimum inhibitory concentration (MIC) of 0.8 mg/mL. Investigation on the action mechanism of lipopeptides showed they could change the morphology of mycelia, damage the cell membrane, lower the content of ergosterol and increase the relative conductivity of membrane, cause nucleic acid and proteins leaking out from the cells, and disrupt the cell membrane permeability. Furthermore, metabolomic analysis of F. graminearum revealed the significant differences in the expression of 100 metabolites between the lipopeptides treatment group and the control group, which were associated with various metabolic pathways, mainly including amino acid biosynthesis, pentose, glucuronate and glycerophospholipid metabolism. In addition, strain ZK-9 inhibited Fusarium crown rot (FCR) with a biocontrol efficacy of 82.14 % and increased the plant height and root length by 24.23 % and 93.25 %, respectively. Moreover, the field control efficacy of strain ZK-9 on Fusarium head blight (FHB) was 71.76 %, and the DON content in wheat grains was significantly reduced by 69.9 %. This study puts valuable insights into the antifungal mechanism of lipopeptides against F. graminearum, and provides a promising biocontrol agent for controlling F. graminearum.

One stone two birds: Endophytes alleviating trace elements accumulation and suppressing soilborne pathogen by stimulating plant growth, photosynthetic potential and defense related gene expression.

In the present investigation, we utilized zinc nanoparticles (Zn-NPs) and bacterial endophytes to address the dual challenge of heavy metal (HM) toxicity in soil and Rhizoctonia solani causing root rot disease of tomato. The biocontrol potential of Bacillus subtilis and Bacillus amyloliquefaciens was harnessed, resulting in profound inhibition of R. solani mycelial growth and efficient detoxification of HM through strong production of various hydrolytic enzymes and metabolites. Surprisingly, Zn-NPs exhibited notable efficacy in suppressing mycelial growth and enhancing the seed germination (%) while Gas chromatography-mass spectrometry (GC-MS) analysis unveiled key volatile compounds (VOCs) crucial for the inhibition of pathogen. Greenhouse trials underscored significant reduction in the disease severity (%) and augmented biomass in biocontrol-mediated plants by improving photosynthesis-related attributes. Interestingly, Zn-NPs and biocontrol treatments enhanced the antioxidant enzymes and mitigate oxidative stress indicator by increasing H2O2 concentration. Field experiments corroborated these findings, with biocontrol-treated plants, particularly those receiving consortia-mediated treatments, displayed significant reduction in disease severity (%) and enhanced the fruit yield under field conditions. Root analysis confirmed the effective detoxification of HM, highlighting the eco-friendly potential of these endophytes and Zn-NPs as fungicide alternative for sustainable production that foster soil structure, biodiversity and promote plant health.

Utilizing Haematococcus pluvialis to simulate animal meat color in high-moisture meat analogues: Texture quality and color stability.

The effect of Haematococcus pluvialis (HP) (0.25∼1.25 %) as a colorant during high moisture extrusion (50 %) on the texture and microstructural properties of soy protein-based high moisture meat analogs (HMMA) was evaluated. Furthermore, the stability of HP-induced meat like color of the HMMA as a function of light exposure, freeze/thawing, frozen storage and cooking temperature and duration was investigated. The addition of HP reduced the elasticity of HMMA but enhanced its hardness, chewiness, and resilience. HP addition at low levels promoted the flexible and disordered regions within the protein secondary structure while excessive HP addition was unfavorable for protein cross-linking. The optimal degree of texturization was achieved with 0.75 % HP. Sensory evaluations revealed that HMMA with 1 %HP had a color similar to fresh beef sirloin, while HMMA with 0.25 % HP had a color closer to fresh pork loin. Light exposure induced the greatest color loss of the meat analogs compared with the cooking and frozen storage. The a* value of HMMA containing 1.25 % HP decreased by 30 % during the 14 days of light exposure. Frozen storage at darkness efficiently preserved the meat-like color of the extrudates. Overall, HP was found as promising colorant for HMMA production but the storage condition of the extrudates should be carefully optimized.

Fructose uptake in Bifidobacterium longum NCC2705 is mediated by an ATP-binding cassette transporter.

Recently, a putative ATP-binding cassette (ABC) transport system was identified in Bifidobacterium longum NCC2705 that is highly up-regulated during growth on fructose as the sole carbon source. Cloning and expression of the corresponding ORFs (bl0033-0036) result in efficient fructose uptake by bacteria. Sequence analysis reveals high similarity to typical ABC transport systems and suggests that these genes are organized as an operon. Expression of FruE is induced by fructose, ribose, or xylose and is able to bind these sugars with fructose as the preferred substrate. Our data suggest that BL0033-0036 constitute a high affinity fructose-specific ABC transporter of B. longum NCC2705. We thus suggest to rename the coding genes to fruEKFG and the corresponding proteins to FruE (sugar-binding protein), FruK (ATPase subunit), FruF, and FruG (membrane permeases). Furthermore, protein-protein interactions between the components of the transporter complex were determined by GST pulldown and Western blot analysis. This revealed interactions between the membrane subunits FruF and FruG with FruE, which in vivo is located on the external side of the membrane, and with the cytoplasmatic ATPase FruK. This is in line with the proposed model for bacterial ABC sugar transporters.

The seed microbiomes of staple food crops.

The scientific community increasingly recognized that seed microbiomes are important for plant growth and nutrition. The versatile roles and modulating properties that microbiomes hold in the context of seeds seem to be an inherited approach to avert adverse conditions. These discoveries attracted extensive interest, especially in staple food crops (SFCs) where grain was consumed as food. Along with the rapid expansion of population and industrialization that posed a severe challenge to the yield of SFCs, microbiologists and botanists began to explore and engineer seed microbiomes, for safer and more fruitful grain production. To utilize seed microbiomes, we present an overall review of the most updated scientific literature on three representative SFCs (wheat, rice and maize) using the 5W1H (Which, Where, What, Why, When and How) method that provides a comprehensive understanding of the issue. These include which factors determine the composition of seed microbiomes? Where do seed microbiomes come from? What are these seed microbes? Why do these microbes choose seeds as their destination and when do microbes settle down and become seed communists? In addition, how do seed microbiomes work and can be manipulated effectively? Therefore, answering the aforementioned questions regarding SFCs seed microbiomes remain fundamental in bridging endophytic research gaps and harnessing their ecological services.

Way to efficient microbial paclitaxel mass production.

The microbial synthesis of paclitaxel is attractive for its short-cycle, cost-effectiveness, and sustainability. However, low paclitaxel productivity, depleted capacity during subculture and storage, and unclear biosynthesis mechanisms restrain industrial microbial synthesis. Along with the isolation of various paclitaxel-producing microorganisms and the development of versatile molecular tools, tremendous promises for microbial paclitaxel synthesis have become increasingly prominent. In this review, we summarize the progress of microbial synthesis of paclitaxel in recent years, focusing on paclitaxel-producing endophytes and representative engineering microorganism hosts that were used as chassis for paclitaxel precursor synthesis. Numerous wide-type microbes can manufacture paclitaxel, and fermentation process optimization and strain improvement can greatly enhance the productivity. Engineered microbes can efficiently synthesize precursors of paclitaxel by introducing exogenous synthetic pathway. Mining paclitaxel synthetic pathways and genetic manipulation of endophytes will accelerate the construction of microbial cell factories, indefinitely contributing to paclitaxel mass production by microbes. This review emphasizes the potential and provides solutions for efficient microbial paclitaxel mass production.

Mining Lactonase Gene from Aflatoxin B1-Degrading Strain Bacillus megaterium and Degrading Properties of the Recombinant Enzyme.

Mycotoxins are toxic secondary metabolites mainly produced by filamentous fungal species that commonly contaminate food and feed. Aflatoxin B1 (AFB1) is extremely toxic and seriously threatens the health of humans and animals. In this work, the Bacillus megaterium HNGD-A6 was obtained and showed a 94.66% removal ability of AFB1 by employing extracellular enzymes as the degrading active substance. The degradation products were P1 (AFD1, C16H14O5) and P2 (C14H16N2O2), and their toxicity was greatly reduced compared to that of AFB1. The AttM gene was mined by BlastP comparison and successfully expressed in Escherichia coli BL21. AttM could degrade 86.78% of AFB1 at pH 8.5 and 80 °C, as well as 81.32% of ochratoxin A and 67.82% of zearalenone. The ability of AttM to degrade a wide range of toxins and its resistance to high temperatures offer the possibility of its use in food or feed applications.

LuxS-dependent AI-2 regulates versatile functions in Enterococcus faecalis V583.

Bacteria utilize a quorum sensing (QS) system to coordinate gene expression by monitoring the concentration of molecules known as autoinducers (AI). In the present study, we confirmed the presence of a LuxS/AI-2 dependent QS system in vancomycin-resistant Enterococcus faecalis V583. Then, the cellular targets controlled by AI-2 were identified by comparative proteomics analysis in order to elucidate the possible role of AI-2 in E. faecalis. Results demonstrated 15 proteins that are differentially expressed upon the addition of AI-2, including proteins involved in metabolism, translation, energy production and/or conversion, and cell wall biogenesis. Glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase associated with carbohydrate metabolism and energy production were up-regulated upon inducing by AI-2. In addition, externally added AI-2 could down-regulate acetyl-coenzyme A carboxylase and ornithine carbamoyltransferase, two key enzyme involved in metabolism. All these data suggest that AI-2 signaling may play a role in the regulation of a number of important metabolic properties of E. faecali. We further investigated the role of AI-2 in biofilm formation by E. faecalis, showing the addition of AI-2 to E. faecalis V583 cultures resulted in increased biofilm formation. Our results provide important clues to the role of a LuxS/AI-2 dependent QS system in vancomycin-resistant E. faecalis.

Accessing the inaccessible: molecular tools for bifidobacteria.

Bifidobacteria are an important group of the human intestinal microbiota that have been shown to exert a number of beneficial probiotic effects on the health status of their host. Due to these effects, bifidobacteria have attracted strong interest in health care and food industries for probiotic applications and several species are listed as so-called "generally recognized as safe" (GRAS) microorganisms. Moreover, recent studies have pointed out their potential as an alternative or supplementary strategy in tumor therapy or as live vaccines. In order to study the mechanisms by which these organisms exert their beneficial effects and to generate recombinant strains that can be used as drug delivery vectors or live vaccines, appropriate molecular tools are indispensable. This review provides an overview of the currently available methods and tools to generate recombinant strains of bifidobacteria. The currently used protocols for transformation of bifidobacteria, as well as replicons, selection markers, and determinants of expression, will be summarized. We will further discuss promoters, terminators, and localization signals that have been used for successful generation of expression vectors.

Assessment of the bifidogenic and antibacterial activities of xylooligosaccharide.

Xylooligosaccharide (XOS) is an attractive prebiotic mainly due to its bifidogenic effect. However, commercial XOS with different compositions is often applied in the food industry at different doses without specifications. In this study, we evaluated the bifidogenic activity of XOS at different doses with either mixtures or pure fractions with different degrees of polymerization (DP), using three strains of Bifidobacterium spp., including B. breve ATCC 15700, B. bifidum ATCC 29521, and B. animalis subsp. lactis HN019. Three growth indicators showed strain-specific bifidogenic activity of XOS, and the activity was both dose- and fraction-dependent as only certain fractions stimulated significant growth. Adding 0.25% XOS (w/v) also promoted increase in total bifidobacterial population of rat fecal samples fermented in vitro. Albeit the antibacterial activity of XOS fractions can be demonstrated, significant growth inhibition can only be achieved when 4.0% XOS mixture was added in Staphylococcus aureus ATCC 6538 pure culture. In contrast, in the presence of B. lactis HN019, 1.0% XOS showed significant antibacterial activity against S. aureus ATCC 6538 in milk. In addition, RNA sequencing suggested downregulation of genes involved in S. aureus ATCC 6538 infection, pathogenesis, and quorum sensing, by XOS. In conclusion, the report urges scientific specifications on XOS chemistry for its effective application as a novel food ingredient or functional food and provides novel insights into its bifidogenic and antibacterial activities.

Halotolerant Bacillus altitudinis WR10 improves salt tolerance in wheat via a multi-level mechanism.

Soil salinity is an important abiotic stress factor that seriously affects the crop growth and yield. Use of plant-derived microorganisms is a promising strategy to alleviate salt stress. In a previous study, the endophytic strain Bacillus altitudinis WR10 isolated from wheat roots showed high salt resistance. In this study, we investigated the efficacy of WR10 in improving the salt tolerance of wheat and its potential mechanisms using a hydroponic test. Under salt stress, WR10 inoculation significantly increased the lengths and dry weights of the roots and shoots, indicating that WR10 improves wheat salt tolerance at the seedling stage. WR10 inoculation significantly reduced Na+ accumulation and enhanced K+, P, and Ca2+ uptake in salt-stressed plants, which can be attributed to the upregulated gene expression of H+-ATPase as well as the P-solubilizing and biofilm-producing characteristics of WR10. At the transcriptional level, L-ascorbate peroxidase (APX), glutathione (GSH) synthetase related to GSH biosynthesis, and phenylpropanoid biosynthesis genes (CYP73A, 4CL, and CAD) were significantly upregulated, whereas those of GSH metabolism genes (glutathione S-transferase and gamma-glutamyltranspeptidase) were significantly downregulated in WR10-applied wheat roots under salt stress. These changes increased the APX activity and GSH levels and resulted in a decrease in hydrogen peroxide levels. Additionally, a decrease in proline content was observed in WR10-inoculated plants under salt stress because of WR10-induced upregulation of proline dehydrogenase gene expression. These results provide supporting evidence that WR10 improves wheat salt tolerance via more than one mechanism and open a window of opportunity for WR10 application in salinized soil.

Comparative analysis of the microbiotas and physicochemical properties inside and outside medium-temperature Daqu during the fermentation and storage.

Medium-temperature Daqu (MT-Daqu), a saccharification-fermentation agent and aroma-producing agent, is used to produce Chinese strong-flavor Baijiu. Many related studies have been published; however, less is known about microbial community and quality properties inside and outside the MT-Daqu from fermentation to storage. Here, along with determining the physicochemical index, the microbial community of MT-Daqu was investigated using both culture-dependent and culture-independent methods during 31 days of fermentation and 4 months of storage. Volatile compounds of mature MT-Daqu were analyzed using headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS). The results indicated obvious variation in the microbial community due to the changes in environmental conditions, and the physicochemical indices shifted from fluctuations in the fermentation period to relative stability after storage for 3 months. Moreover, the microbial counts and physicochemical indices of the inner layers of MT-Daqu differed from those of the outer layers. The dominant communities, including the bacterial phyla Firmicutes, Proteobacteria, and Actinobacteria and the fungal phyla Ascomycota and Mucoromycota, showed different abundances in the two parts of the mature MT-Daqu, and different microbial communities were enriched in both parts. Additionally, pyrazines and alcohols were the most abundant volatile aroma compounds in the mature MT-Daqu.

Acrylamide induced glucose metabolism disorder in rats involves gut microbiota dysbiosis and changed bile acids metabolism.

Acrylamide (AA) is a common food contaminant that causes glucose metabolism disorders (GMD). However, the underlying mechanism remains unclear. Female Sprague Dawley (SD) rats were treated with AA via gavage for 21 days, and the glucose and insulin levels, gut microbiota, intestinal barrier, and metabolism were analyzed. The results revealed that AA elevated serum glucose levels, reduced insulin levels and caused intestinal barrier injury. The 16S amplicon sequencing and non-targeted metabolomics showed that AA induced gut microbiota dysbiosis and bile acids (BAs) metabolism disorder. Specifically, AA decreased the abundance of Lactobacillus and Bacteroides in the cecal contents, and increased the cholic acid (CA) content in feces. Meanwhile, the expression of ileum apical sodium-dependent bile acid transporter (ASBT) responsible for CA reabsorption was suppressed. Further analysis indicated that BAs sensing nuclear receptor farnesoid X receptor (FXR) gene was activated and glucagon-like peptide-1 (GLP-1) which stimulates insulin secretion was downregulated. In addition, activation of FXR increased the expression of fibroblast growth factor 15 (FGF15), which resulted in the inhibition of hepatic BAs synthesis. Overall, this study demonstrated that AA-induced GMD is associated with the gut-microbiota-CA-FXR/GLP-1 axis. These findings add new knowledge to the AA-induced GMD and provide a basis for potential AA toxicity mitigation by manipulation of the gut microbiota.