Curcumin is widely recognized for its health benefits, though the role of gut microbiota in its metabolic transformation was not well studied. In this study, bacterial strains capable of metabolizing curcumin were isolated from human stool samples. Using 16S rRNA and whole-genome sequencing, two novel strains (Clostridium butyricum UMA_cur1 and Escherichia coli UMA_cur2) were identified. In addition, the metabolic products were analyzed using liquid chromatography-mass spectrometry. These strains efficiently converted curcumin into dihydro-curcumin (DHC) and tetrahydro-curcumin (THC). Notably, E. coli UMA_cur2 also produced hexahydro-curcumin (HHC) and octahydro-curcumin (OHC), marking the first identification of a strain capable of such transformations. The absence of the YncB gene (typically involved in curcumin conversion) in C. butyricum UMA_cur1 suggests an alternative metabolic pathway. Curcumin metabolism begins during the stationary growth phase, indicating that it is not crucial for primary growth functions. Furthermore, E. coli UMA_cur2 produced these metabolites sequentially, starting with DHC and THC and progressing to HHC and OHC. These findings identified two novel strains that can metabolize curcumin to hydrogenated metabolites, which enhance our understanding of the interaction between curcumin and gut microbiota.

BACKGROUND: Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics.
OBJECTIVE: To develop gut bacterial subtypes and explore potential microbial targets for CRC.
METHODS: Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA).
RESULTS: Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes.
CONCLUSIONS: Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

BACKGROUND: The role of gut bacteria in preventing and delaying osteoporosis has been studied. However, the causal relationship between gut bacteria, plasma proteins, circulating metabolites and osteoporosis (OP) risk has not been fully revealed.
METHODS: In this study, a two-sample Mendelian randomization study (MR) approach was used to assess the causal associations between gut bacteria, plasma proteins and circulating metabolites, and osteoporosis risk using Genome Wide Association Study (GWAS) data from gut bacteria(n=8208), plasma proteins(n=2263), circulating metabolites (n=123), and osteoporosis (3203 cases and 16380452 controls). Inverse-variance weighted (IVW) was used as the main analytical method to estimate the MR causal effect and to perform directional sensitivity analysis of causality. Finally, the mediating effect values for the influence of gut flora on OP pathogenesis through circulating metabolites were calculated by univariate MR analysis, and multivariate MR analysis. Next, we evaluated the effect of Phosphatidylcholine on the osteogenic function of bone marrow mesenchymal stem cells (BMSCs) through relevant experiments, including Edu detection of cell proliferation, alkaline phosphatase (ALP) staining, Alizarin red staining to evaluate osteogenic function, qPCR and WB detection of osteogenic differentiation related gene expression.
RESULTS: A total of 9 gut microbial taxa, 15 plasma proteins and eight circulating metabolites were analysed for significant causal associations with the development of OP. Significant causal effects of 7 on gut bacteria, plasma proteins and circulating metabolites were analysed by univariate MR analysis and these results were used as exposure factors for subsequent multivariate MR. Multivariate MR analyses yielded a significant effect of circulating metabolites Phosphatidylcholine and other cholines on OP (P<0.05). Further mediation effect analysis showed that the mediation effect of Bifidobacteriaceae affecting OP through the circulating metabolite Phosphatidylcholine and other cholines was -0.0224, with a 95% confidence interval for the mediation effect that did not include 0, and the complete mediation effect was significant. Phosphatidylcholine can promote BMSCs proliferation and osteogenesis.
CONCLUSIONS: Our study demonstrated significant causal associations of gut bacteria, plasma proteins and circulating metabolites on OP, and that Bifidobacteriaceae affect OP through the circulating metabolites Phosphatidylcholine and other cholines. Phosphatidylcholine affects the osteogenic ability of BMSCs. Further exploration of potential microbiota-associated mechanisms of bone metabolism may offer new avenues for osteoporosis prevention and treatment of osteoporosis.

Gut microbiota is a diverse community of microorganisms that constantly work to protect the gut against pathogens. Salmonella stands out as a notorious foodborne pathogen that interacts with gut microbes, causing an imbalance in the overall composition of microbiota and leading to dysbiosis. This review focuses on the interactions between Salmonella and the key commensal bacteria such as E. coli, Lactobacillus, Clostridium, Akkermansia, and Bacteroides. The review highlights the role of these gut bacteria and their synergy in combating Salmonella through several mechanistic interactions. These include the production of siderophores, which compete with Salmonella for essential iron; the synthesis of short-chain fatty acids (SCFAs), which exert antimicrobial effects and modulate the gut environment; the secretion of bacteriocins, which directly inhibit Salmonella growth; and the modulation of cytokine responses, which influences the host\'s immune reaction to infection. While much research has explored Salmonella, this review aims to better understand how specific gut bacteria engage with the pathogen, revealing distinct defense mechanisms tailored to each species and how their synergy may lead to enhanced protection against Salmonella. Furthermore, the combination of these commensal bacteria could offer promising avenues for bacteria-mediated therapy during Salmonella-induced gut infections in the future.

Osmia excavata is an excellent pollinator in nature and plays a vital role in the conservation of agro-ecosystems and food security. Given the important role of the gut bacterial community in host health and regulation of host growth and development, using 16S rRNA gene sequencing data, the present study explored the composition of the gut bacterial community and its diversity at different life stages (eggs, young larvae, old larvae, young pupae, old pupae, and 1-day-old adults in cocoons) of the solitary bee Osmia excavata. The results showed that the core phyla in the gut of O. excavata at different life stages were Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota, and the core genera were Sodalis, Tyzzerella, and Ralstonia. The highest intestinal bacterial diversity was found in the Egg period, and the lowest bacterial alpha diversity was found in the 1-day-old Adult period; the bacterial diversity of O. excavata showed a process of decreasing, as it was growing from the Egg period to the 1-day-old Adult period. Our study found that O. excavata undergoes a significant change in the structure of the gut flora when it grows from the young pupae to old pupae stage, a period of growth that coincides with the process of cocooning and isolation from the external environment after food depletion. This suggests that food and environmental factors are key contributors to the structure of the bacterial community in the gut of solitary bees.

Antibiotic resistance genes (ARGs) carried by gut pathogens may pose a threat to the host and ecological environment. However, few studies focus on the effects of cold stress on intestinal bacteria and ARGs in plateau animals. Here, we used 16S rRNA gene sequencing and gene chip technique to explore the difference of gut microbes and ARGs in plateau pika under 4 °C and 25 °C. The results showed that tetracycline and aminoglycoside resistance genes were the dominant ARGs in pika intestine. Seven kinds of high-risk ARGs (aadA-01, aadA-02, ermB, floR, mphA-01, mphA-02, tetM-02) existed in pika\'s intestine, and cold had no significant effect on the composition and structure of pika\'s intestinal ARGs. The dominant phyla in pika intestine were Bacteroidetes and Firmicutes. Cold influenced 0.47 % of pika intestinal bacteria in OTU level, while most other bacteria had no significant change. The diversity and community assembly of intestinal bacteria in pika remained relatively stable under cold conditions, while low temperature decreased gut microbial network complexity. In addition, low temperature led to the enrichment of glycine biosynthesis and metabolism-related pathways. Moreover, the correlation analysis showed that eight opportunistic pathogens (such as Clostridium, Staphylococcus, Streptococcus, etc.) detected in pika intestine might be potential hosts of ARGs.

Insects and their gut bacteria form a tight and beneficial relationship, especially in utilization of host nutrients. The red turpentine beetle (RTB), a destructive and invasive pine pest, employs mutualistic microbes to facilitate its invasion success. However, the molecular mechanism underlying the utilization of nutrients remains unknown. In this study, we found that gut bacteria are crucial for the utilization of D-glucose, a main carbon source for RTB development. Downstream assays revealed that gut bacteria-induced gut hypoxia and the secretion of riboflavin are responsible for RTB development by regulating D-glucose transport via the activation of a hypoxia-induced transcription factor 1 (Hif-1α). Further functional investigations confirmed that Hif-1α mediates glucose transport by direct upregulation of two glucose transporters (ST10 and ST27), thereby promoting RTB development. Our findings reveal how gut bacteria regulate the development of RTB, and promote our understanding of the mutualistic relationship of animals and their gut bacteria.

BACKGROUND: Gut bacteria are crucial in influencing insect development and even phenotypic plasticity. The yellow peach moth Conogethes punctiferalis, as a significant borer pest, has been the subject of limited reports regarding the structural and diversification changes in its gut microbiota during feeding, and their potential impacts on the growth and development of the host insects.
RESULTS: This study, employing 16S rRNA sequencing, demonstrates distinct shifts in the larvae gut microbiome of C. punctiferalis between different feeding stages, highlighting a pronounced diversity in the early-instar with Enterococcus as a predominant genus in laboratory populations. Through in vitro cultivation and sequencing, three bacterial strains - Micrococcus sp., Brevibacterium sp. and Enterococcus mundtii - were isolated and characterized. Bioassays revealed that E. mundtii-infused corn significantly boosts early-instar larval growth, enhancing both body length and weight. Quantitative PCR and spectrophotometry confirmed a higher abundance of E. mundtii in younger larvae, correlating with increased digestive enzyme activity and total protein levels.
CONCLUSIONS: This study reveals the heightened gut microbiota diversity in early instars of C. punctiferalis larvae, highlighting that Enterococcus represent a predominant bacteria in laboratory populations. In vitro cultivation and bioassays unequivocally demonstrate the significant role of the cultivable gut bacteria E. mundtii in promoting the growth of early-instar larva. These findings provide a solid theoretical foundation for advancing the comprehension of the intricate interactions between gut microbiota and insect hosts, as well as for the development of eco-friendly pest control technologies based on targeted manipulation of insect gut microbial communities. © 2024 Society of Chemical Industry.

The pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [14C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[14C]Aficamten accounted for ∼80% and a hydroxylated metabolite (M1) accounted for ∼12% of total radioactivity in plasma over 48-h (AUC0-48). Plasma tmax was 4-h and the t1/2 of total plasma radioactivity was 5.8-h.Tissues showing highest Cmax exposures were myocardium and semitendinosus muscle.Most [14C]aficamten-derived radioactivity was excreted within 48-h post-administration. Mean cumulative recovery in urine and faeces over 168-h was 8.3% and 90.7%, respectively.In urine and bile, unchanged aficamten was detected at <0.1 and <0.2% of dose, respectively; however, based on total radioactivity excreted in urine (8.0%) and bile (51.7%), approximately 60% of dose was absorbed.[14C]Aficamten was metabolised by hydroxylation with subsequent glucuronidation where the most abundant metabolite recovered in bile was M5 (35.2%), the oxygen-linked glucuronide of hydroxylated aficamten (M1a). The major metabolite detected in faeces was a 1,2,4-oxadiazole moiety ring-cleaved metabolite (M18, 35.3%), shown to be formed from the metabolism of M5 in incubations with rat intestinal contents solution.

BACKGROUND: More than 90% of colorectal cancer (CRC) arises from advanced adenomas (AA) and gut microbes are closely associated with the initiation and progression of both AA and CRC.
OBJECTIVE: To analyze the characteristic microbes in AA.
METHODS: Fecal samples were collected from 92 AA and 184 negative control (NC). Illumina HiSeq X sequencing platform was used for high-throughput sequencing of microbial populations. The sequencing results were annotated and compared with NCBI RefSeq database to find the microbial characteristics of AA. R-vegan package was used to analyze α diversity and β diversity. α diversity included box diagram, and β diversity included Principal Component Analysis (PCA), principal co-ordinates analysis (PCoA), and non-metric multidimensional scaling (NMDS). The AA risk prediction models were constructed based on six kinds of machine learning algorithms. In addition, unsupervised clustering methods were used to classify bacteria and viruses. Finally, the characteristics of bacteria and viruses in different subtypes were analyzed.
RESULTS: The abundance of Prevotella sp900557255, Alistipes putredinis, and Megamonas funiformis were higher in AA, while the abundance of Lilyvirus, Felixounavirus, and Drulisvirus were also higher in AA. The Catboost based model for predicting the risk of AA has the highest accuracy (bacteria test set: 87.27%; virus test set: 83.33%). In addition, 4 subtypes (B1V1, B1V2, B2V1, and B2V2) were distinguished based on the abundance of gut bacteria and enteroviruses (EVs). Escherichia coli D, Prevotella sp900557255, CAG-180 sp000432435, Phocaeicola plebeiuA, Teseptimavirus, Svunavirus, Felixounavirus, and Jiaodavirus are the characteristic bacteria and viruses of 4 subtypes. The results of Catboost model indicated that the accuracy of prediction improved after incorporating subtypes. The accuracy of discovery sets was 100%, 96.34%, 100%, and 98.46% in 4 subtypes, respectively.
CONCLUSIONS: Prevotella sp900557255 and Felixounavirus have high value in early warning of AA. As promising non-invasive biomarkers, gut microbes can become potential diagnostic targets for AA, and the accuracy of predicting AA can be improved by typing.