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Accumulating studies have highlighted the great potential of postbiotics in alleviating diseases and protecting host health. Compared with traditional functional foods (such as probiotics and prebiotics), postbiotics have the advantages of a single composition, high physiological activity, long shelf life, easy absorption, and high targeting, etc. The development of postbiotics has led to a wide range of potential applications in functional food and drug development. However, the lack of clinical trial data, mechanism analyses, safety evaluations, and effective regulatory frameworks has limited the application of postbiotic products. This review describes the definition, classification, sources, and preparation methods of postbiotics, the progress and mechanism of preclinical and clinical research in improving host diseases, and their application in food. Strengthen understanding of the recognition and development of related products to lay a theoretical foundation.

Colistin used to be regarded as the last-resort treatment for the infection caused by multidrug-resistant gram-negative bacteria. However, the emergence and widespread of mcr-1 seriously reduce the clinical effectiveness of colistin, constituting a serious threat to global public health. Due to the difficulties in the development of new antibiotics, restoring antibiotic susceptibility with adjuvants is undoubtedly a rational option. As naturally occurring compounds, resveratrol and capsaicin could be extracted from many natural plants, due to various antimicrobial properties, they have received significant attention. Herein, the synergistic activity of colistin combined with resveratrol and capsaicin against mcr-1-positive Escherichia coli were investigated by checkerboard method and time-killing assays. The in-depth molecular mechanisms were elucidated by scanning electron microscopy, fluorescent probe experiments, transcriptome and metabolome analysis. Molecular docking assay was taken to analyse potential interactions between resveratrol/capsaicin and MCR-1. Finally, the in vivo efficacy of combined therapy against mcr-1-positive Escherichia coli was assessed. Our results demonstrated that colistin combined with resveratrol and capsaicin acted synergistic activity against mcr-1-positive Escherichia coli both in vivo and in vitro. Further mechanistic studies showed that the combined therapy could exacerbate cell membrane damage, increase membrane permeability, disrupt the homeostasis of PMF, inhibit ATP synthesis, and efflux pump activity. In addition, the combined therapy could inhibit central carbon metabolism, and reduce tricarboxylic acid cycle and oxidative phosphorylation. Moreover, molecular docking assay revealed resveratrol/capsaicin could bind to MCR-1 stably. Our study indicated that colistin in combination with resveratrol and capsaicin as a novel therapy could provide a trustworthy foundation to establish the treatment plan for mcr-1-positive Escherichia coli.

Dietary fiber targets the regulation of the intestinal flora and thus affects host health, however, the complex relationship between these factors lacks direct evidence. In this study, the regulatory effects of Konjac glucomannan (KGM) on key metabolites of host intestinal flora were examined by using in vitro fermentation. The results showed that KGM could be utilized by the intestinal flora, which inhibited the relative abundance of Paeniclostridium, Lachnoclostridium, Phascolarctobacterium, and Bacteroides and enriched the relative abundance of Desulfovibrio, Sutterella, etc. Fermentation is accompanied by the production of short-chain acids, including acetic and propionic acids. Metabolomics revealed that KGM significantly promoted amino acid metabolism, lipid metabolism, and the biosynthesis of other secondary metabolites. Correlation analysis results showed that the increase of panose and N-(1-carboxy-3-carboxanilidopropyl) alanylproline content was positively correlated with the relative abundance of Megamonas. These results provide evidence that KGM affects host health by regulating gut microbiota and its metabolites.

Stachyose is a prebiotic that traditionally extracted from plants, such as vegetable. It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota, but the mechanism has been unclear. This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis (UC). The results indicated that the administration of stachyose could recover the body weight, protect against the colonic tissue damage, reduce the pro-inflammatory cytokines levels, and reverse the histological abnormalities in UC mice. Oral stachyose could restore DSS-induced disturbance in intestinal bacteria. Besides, the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice. Also, a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera. Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.

In this paper we studied rigidity results for closed vacuum static spaces. By using the maximum principle, we achieved rigidity theorems under some pointwise inequalities and showed that the squared norm of the Ricci curvature tensor was discrete.

In this paper, we will develop a different technique to study the rigidity of complete $ \lambda $-translators $ x:M^{2} \rightarrow \mathbb R^{3} $ with the non-zero constant gauss curvature in the Euclidean space $ \mathbb R^{3} $.

With the threshold for crop growth data collection having been markedly decreased by sensor miniaturization and cost reduction, unmanned aerial vehicle (UAV)-based low-altitude remote sensing has shown remarkable advantages in field phenotyping experiments. However, the requirement of interdisciplinary knowledge and the complexity of the workflow have seriously hindered researchers from extracting plot-level phenotypic data from multisource and multitemporal UAV images. To address these challenges, we developed the Integrated High-Throughput Universal Phenotyping (IHUP) software as a data producer and study accelerator that included 4 functional modules: preprocessing, data extraction, data management, and data analysis. Data extraction and analysis requiring complex and multidisciplinary knowledge were simplified through integrated and automated processing. Within a graphical user interface, users can compute image feature information, structural traits, and vegetation indices (VIs), which are indicators of morphological and biochemical traits, in an integrated and high-throughput manner. To fulfill data requirements for different crops, extraction methods such as VI calculation formulae can be customized. To demonstrate and test the composition and performance of the software, we conducted case-related rice drought phenotype monitoring experiments. In combination with a rice leaf rolling score predictive model, leaf rolling score, plant height, VIs, fresh weight, and drought weight were efficiently extracted from multiphase continuous monitoring data. Despite the significant impact of image processing during plot clipping on processing efficiency, the software can extract traits from approximately 500 plots/min in most application cases. The software offers a user-friendly graphical user interface and interfaces for customizing or integrating various feature extraction algorithms, thereby significantly reducing barriers for nonexperts. It holds the promise of significantly accelerating data production in UAV phenotyping experiments.

Lactulose is a common component in foods. However, the effect of lactulose on intestinal flora and overall metabolic levels remains unclear. Therefore, this study aims to explore the regulative role of lactulose on intestinal flora and serum metabolites via in vitro simulated colonic fermentation model and in vivo colitis mouse model. The results showed that lactulose significantly enriched beneficial bacteria including Dubosiella and Bifidobacterium, and reduced pathogenic bacteria such as Fusobacterium. Moreover, lactulose significantly inhibited dextran sodium sulfate-induced body weight loss, colon shortening, colonic inflammatory infiltration, and pro-inflammatory cytokines IL-6, TNF-α, IL-17, and IL-1β. Lactulose significantly affected serum metabolome in colitis mice and total 24 metabolites representing a high inter-group difference were obtained. Correlation analysis revealed that the changes in serum metabolites were closely associated with the role of intestinal flora, and thus affected phenotypic indicators. Our study provides a reference for nutritional characteristics and application scenarios of dietary lactulose.

Abstract Background Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer. Methods The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed. Results In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells. Conclusion Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer.

Tumor metastasis remains a major challenge for patients with breast cancer. Aberrant epigenetic factor lysine‐specific demethylase 6B (KDM6B) has been associated with tumor progression. Here, we show that KDM6B is significantly down‐regulated in human breast cancer tissues, and its low expression is associated with poor prognosis of patients with breast cancer. Furthermore, overexpression of KDM6B remarkably inhibited cell proliferation, invasion, migration and epithelial–mesenchymal transition markers of breast cancer cells in vitro and tumor growth and lung metastasis in vivo. Notably, the expression of KDM6B in breast cancer tissues was negatively correlated with that of β‐catenin, and overexpression of KDM6B decreased the expression of β‐catenin and its accumulation in the nucleus of breast cancer cells. Overall, our findings provide novel insights into suppression of metastasis of breast cancer cells by KDM6B via β‐catenin and suggest involvement of the KDM6B‐Wnt/β‐catenin axis in breast cancer progression.

Abstract Recent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into the gene expression profiles in early-stage kidney development. However, comprehensive gene expression profiles from mid- and late-stage kidney development are lacking. In the present study, by using the scRNA-seq technique, we analyzed 54,704 rat kidney cells from just after birth to adulthood (six time points: postnatal days 0, 2, 5, 10, 20, and 56) including the mid and late stages of kidney development. Twenty-five original clusters and 13 different cell types were identified during these stages. Gene expression in these 13 cell types was mapped, and single cell atlas of the rat kidney from birth to maturity ( http://youngbearlab.com ) was built to enable users to search for a gene of interest and to evaluate its expression in different cells. The variation trend of six major types of kidney cells—intercalated cells of the collecting duct (CD-ICs), principal cells of the collecting duct (CD-PCs), cells of the distal convoluted tubules (DCTs), cells of the loop of Henle (LOH), podocytes (PDs), and cells of the proximal tubules (PTs)—during six postnatal time points was demonstrated. The trajectory of rat kidney development and the order of induction of the six major types of kidney cells from just after birth to maturity were determined. In addition, features of the dynamically changing genes as well as transcription factors during postnatal rat kidney development were identified. The present study provides a resource for achieving a deep understanding of the molecular basis of and regulatory events in the mid and late stages of kidney development.

Four coordination polymers have been synthesized by using Zn(II)/Cd(II) salt and bis(imidazole) ligand in the presence of the different flexible phenylenediacetate isomers under hydrothermal conditions. The flexible trans-conformation pda and biyb ligands in complexes 1, 3, 4 afford the 2D (4,4)-connected layer, which are further stacked in an offset fashion with an ABAB sequence to propagate into a 3D supramolecular architecture through strong C–H···π and C–H⋯O interactions. Differently, the flexible cis-conformation pda and biyb ligands in 2 can be seen as “V” type building block, linking Zn(II) atoms to form a 3D helix network. The structural diversity of these complexes is mainly attributed to the different coordination modes and isomer conformations of the flexible phenylenediacetic acids and bis(imidazole) ligand. The fluorescence property application and mechanisms of four complexes for detecting antibiotic cefixime (CEF) have been researched. Compared with 1, 3, 4 complex 2 has higher quenching percentage, this may be because 2 is a 3D structure with a large hole (18.99 × 20.02 Å window). The detection limits of complexes 1–4 have been measured to be 0.23 μΜ, 0.34 μΜ, 0.37 μΜ, 0.38 μΜ, respectively. The theoretic calculation and UV–vis absorption experiments confirmed that the fluorescence quenching of complexes 1–4 toward cefixime (CEF) should be attributed to the electron transfer and the fluorescence inner filter effect between the fluorescent matter and the analyte.

The poor immunotherapy of pancreatic cancer is mainly due to its complex immunosuppressive microenvironment. The Mediterranean diet contributes to low cancer incidence. Hydroxytyrosol (HT) derived from olive oil has multiple health-promoting effects, but its therapeutic effect on pancreatic cancer remains controversial. Here, we evaluated the inhibitory effect of HT on mouse pancreatic cancer, and the effect of HT on the immune microenvironment. We found that HT can inhibit the proliferation of Panc 02 cells through signal transducer and activator of transcription (STAT) 3/Cyclin D1 signaling pathway. In the tumor-bearing mice treated with HT, the orthotopic pancreatic tumors were suppressed, accompanied by a decrease in the proportion of myeloid-derived suppressor cells (MDSCs) and an increase in the proportion of M1 macrophages. In addition, we found that HT inhibited the expression of immunosuppressive molecules in bone marrow (BM)-derived MDSCs, as well as down-regulated CCAAT/enhancer-binding protein beta (C/EBPβ) and phosphorylation of STAT3. Moreover, HT enhanced the anti-tumor effect of anti-CD47 antibody in vivo. HT combined with plumbagin (PLB) induced more Panc 02 cells death than HT or PLB alone. This combination therapy not only inhibited the accumulation of MDSCs, but also promoted the infiltration of CD4+ and CD8+ T cells in the tumors. In summary, HT is a potential immunomodulatory drug for the treatment of pancreatic cancer.

Background: As common pathogens in the human respiratory tract, fungal-spore-related health risks have been challenging to evaluate properly. This paper presents numerical simulations of particle deposition of Aspergillus niger spores in human nasal cavities. Methods: 30 healthy adults (including 60 nasal chambers) who lived in northwest China were recruited to conduct a nasal cavity numerical simulation using computational fluid dynamics–discrete phase model (CFD-DPM). The deposition rate in each anatomic area and its influencing variables, such as body position and respiratory flow rate, were analyzed. Results: (1) Under a resting condition, only about 5.57% ± 1.51% Aspergillus niger spores were deposited in the nasal cavity, while most of them escaped from the nasopharynx, and 0.31% ± 0.20% spores entered the maxillary sinus; (2) under an exercising condition, spores deposited in the nasal cavity were about 2.09 times as many as that in the resting state; (3) in a lying position, the A. niger spores deposited evenly on the lateral wall of the nasal cavity and the sinus when compared with a standing position. However, the deposition rate in each anatomic area did not change significantly.

The recent progress in engineering topological band structures in optical-lattice systems makes it promising to study fractional Chern insulator states in these systems. Here we consider a realistic finite system of a few repulsively interacting bosons on a square lattice with magnetic flux and sharp edges, as it can be realized in quantum-gas microscopes. We investigate under which conditions a fractional Chern insulator state corresponding to the Laughlin-like state at filling $\nu=1/2$ can be stabilized and its fractional excitations probed. Using numerical simulations, we find an incompressible bulk density at the expected filling for systems, whose linear extent is as small as 6-8 sites. This is a promising result, since such small systems are favorable with respect to the required adiabatic state preparation. Moreover, we also see very clear signatures of excitations with fractional charge in response both to static pinning potentials and dynamical flux insertion. Since the compressible edges, which are found to feature chiral currents, can serve as a reservoir, these observations are robust against changes in the total particle number. Our results suggest that signatures of both a fractional Chern insulator state and its fractional excitations can be found under realistic experimental conditions.

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.

Pancreatic cancer is a digestive tract malignancy that poses a serious threat to human health. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to regulate the tumor immune microenvironment in patients with pancreatic cancer. In this study, icariin was purified from Herba Epimedii using macropores, and its bioactivity against pancreatic cancer was also investigated. We found that icariin has direct inhibitory and immunomodulatory effects on tumor cells. In vitro experiments showed that icariin can inhibit the migration and proliferation of Panc02 pancreatic cancer cells and induce apoptosis. Our in vivo experiments show that icariin inhibits the development of mouse pancreatic cancer by inhibiting tumor-infiltrating M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (MDSCs) (PMN-MDSCs). In addition, icariin inhibits the polarization of RAW 264.7 cells into M2 macrophages by inhibiting the expression of ARG1 and MRC1 and downregulating the IL4-STAT6 signaling pathway. In conclusion, the inhibitory effect of icariin on pancreatic cancer can not only directly affect tumor cells but also inhibit tumor development by regulating the tumor immune microenvironment.

The pancreatic ductal adenocarcinoma (PDAC) microenvironment plays a critical role in the antitumor immune response. 2-arachidonoylglycerol (2-AG) exhibits a direct antitumor effect in various tumor models. However, the immunomodulatory effect of 2-AG on PDAC remains obscure. The aim of this study was to explore the tumor microenvironment response to 2-AG in pancreatic cancer. A PDAC orthotopic tumor model was used to investigate tumor proliferation and the population of immune cells in vivo, including dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), CD8+ T cells and CD4+ T cells. The effect of 2-AG on panc02 cell proliferation and DC2.4 cell maturation in vitro by mediating activation the typical cannabinoid receptors (CB1, CB2) was evaluated by flow cytometry and CCK8. The protein levels of P-STAT6, STAT6 and GADPH were measured by Western blotting.2-AG inhibited pancreatic cancer cell proliferation in tumor bearing mice and panc02 cell. Inhibition of proliferation was blocked by the CB1receptor antagonist (AM251) but not the CB2 receptor antagonist (AM630). In addition, 2-AG promoted DC phenotypic maturation and the production of proinflammatory cytokines by up-regulating p-STAT6. These effects were also blocked by AM251 but not AM630. Moreover, we also provide evidence that 2-AG administration induced the expansion of MDSCs in tumor bearing mice. However, no effect on the population of CD8+ T cells and CD4+ T cells was observed. Our findings support 2-AG exhibited direct antitumor effects via inhibiting pancreatic cancer proliferation and inducing DC phenotypic maturation, but also significantly promoted an immunosuppressive microenvironment via increasing the suppressive immune cell population of MDSCs.

Analysis of the change of the cells in bile is an evolving research field in biliary pathophysiology and has potential value in diagnosis and therapy. However, laboratory studies of cell in bile across the world are scarce. Bile was collected from the clinical patients with cholangiocarcinoma (CC). To optimize the cell separation method in bile of patients with CC, we studied the factors that may affect cell vitality in bile including the dilution buffer, centrifugal force, centrifugal time, and store time and temperature. Then these factors were modified and performance was evaluated by flow cytometry with respect to the percentage and total yield of viable cells. The separated cells from bile were stained with CD3, CD4, CD8, CD56, TCRγ/δ, CD16, CD14, HLA-DR, CD33, CD15, CD11b, lineage cocktail (CD3, CD14, CD19, CD20, and CD56), CD66b, and CD45 antibodies. The different buffer solutions were joined in bile of patients with CC; experiment results show that the different dilutions have nearly no effect on the ratio of cells in bile by flow cytometry. The best centrifugal procedure was 300 g, 10 min. Bile should be stored at 4°C rather than at normal temperature. Our study further showed that the shorter time of the bile storage, the higher viability of the cell, and immune cells existed in cells isolated from bile. Evaluating bile cell viability is necessary to evaluate method performance.

The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four Bifidobacterium adolescentis strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with B. adolescentis of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) B. adolescentis N4_N3, (ii) B. adolescentis Z25, (iii) B. adolescentis 17_3, (iv) B. adolescentis 2016_7_2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The B. adolescentis strains isolated from the feces of elderly humans (B. adolescentis Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn (B. adolescentis N4_N3) increased the body weight of mice. The B. adolescentis strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis- and lipid metabolism-related genes in brown adipose tissue. All the B. adolescentis strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of Bifidobacterium and reduced the development of beta-lactam resistance. In addition, the B. adolescentis strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as Bacteroides, Parabacteroides, and Faecalibaculum. We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as B. adolescentis supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of B. adolescentis can alleviate obesity and modify the gut microbiota of mice. The tested strains of B. adolescentis showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that B. adolescentis from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.

The implementation of static artificial magnetic fields in ultracold atomic systems has become a powerful tool, e.g. for simulating quantum-Hall physics with charge-neutral atoms. Taking an interacting bosonic flux ladder as a minimal model, we investigate protocols for adiabatic state preparation via magnetic flux ramps. Considering the fact that it is actually the artificial vector potential (in the form of Peierls phases) that can be experimentally engineered in optical lattices, rather than the magnetic field, we find that the time required for adiabatic state preparation dramatically depends on which pattern of Peierls phases is used. This can be understood intuitively by noting that different patterns of time-dependent Peierls phases that all give rise to the same magnetic field ramp, generally lead to different artificial electric fields during the ramp. As an intriguing result, we find that an optimal choice allows for preparing the ground state almost instantaneously in the non-interacting system, which can be related to the concept of counterdiabatic driving. Remarkably, we find extremely short preparation times also in the strongly-interacting regime. Our findings open new possibilities for robust state preparation in atomic quantum simulators.

A high-fat diet (HFD) can easily induce obesity and change the gut microbiota and its metabolites. However, studies on the effects of high-fat diets on the host have drawn inconsistent results. In this study, the unexpected results showed that the refined HFD increased gut microbiota diversity and short-chain fatty acids (SCFAs), causing an increase in energy metabolism. Further analysis revealed these changes were caused by the different fiber content in these two diets. Male C57BL/6J mice (4–5 weeks old) were fed either HFD or refined low-fat diet (LFD) for 14 weeks. The metabolic rates, thermogenesis, gut microbiome, and intestinal SCFAs were tested. The HFD triggered obesity and disturbed glucose homeostasis. Mice fed HFD ingested more fiber than mice fed LFD (p < 0.0001), causing higher intestinal SCFA concentrations related to the increased abundances of specific bacteria in the HFD group. Also, the HFD increased metabolic heat and up-regulated thermogenesis genes uncoupling protein 1(Ucp-1), peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) expression in the brown adipose tissue (BAT). It was revealed by 16S rRNA gene sequencing that the HFD increased gut microbial diversity, which enriched Desulfovibrionaceae, Rikenellaceae RC9 gut group, and Mucispirillum, meanwhile, reduced the abundance of Lactobacillus, Bifidobacterium, Akkermansia, Faecalibaculum, and Blautia. The predicted metabolic pathways indicated HFD increased the gene expression of non-absorbed carbohydrate metabolism pathways, as well as the risks of colonization of intestinal pathogens and inflammation. In conclusion, the HFD was obesogenic in male C57BL/6J mice, and increased fiber intake from the HFD drove an increase in gut microbiota diversity, SCFAs, and energy expenditure. Meanwhile, the differences in specific nutrient intake can dissociate broad changes in energy expenditure, gut microbiota, and its metabolites from obesity, raising doubts in the previous studies. Therefore, it is necessary to consider whether differences in specific nutrient intake will interfere with the results of the experiments.