Gut microbiota regulate maturation and mitochondrial function of the nutrient-sensing enteroendocrine cell.

Enteroendocrine cells (EECs) are crucial for sensing ingested nutrients and regulating feeding behavior. How gut microbiota regulate the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis demonstrates that commensal microbiota colonization significantly increases the expression of many genes associated with mitochondrial function. Using new methods to image EEC cytoplasmic and mitochondrial Ca2+ activity in live zebrafish, our data revealed that it is dynamically regulated during the EEC development process. Mature EECs display an increased mitochondrial-to-cytoplasmic Ca2+ ratio. Mitochondria are evenly distributed in the cytoplasm of immature EECs. As EECs mature, their mitochondria are highly localized at the basal membrane where EEC vesicle secretion occurs. Conventionalized (CV) EECs, but not germ-free (GF) EECs, exhibit spontaneous low-amplitude Ca2+ fluctuation. The mitochondrial-to-cytoplasmic Ca2+ ratio is significantly higher in CV EECs. Nutrient stimulants, such as fatty acid, increase cytoplasmic Ca2+ in a subset of EECs and promote a sustained mitochondrial Ca2+ and ATP increase. However, the nutrient-induced EEC mitochondrial activation is nearly abolished in GF zebrafish. Together, our study reveals that commensal microbiota are crucial in supporting EEC mitochondrial function and maturation.

Microbial influences on gut development and gut-brain communication.

The developmental programs that build and sustain animal forms also encode the capacity to sense and adapt to the microbial world within which they evolved. This is abundantly apparent in the development of the digestive tract, which typically harbors the densest microbial communities of the body. Here, we review studies in human, mouse, zebrafish and Drosophila that are revealing how the microbiota impacts the development of the gut and its communication with the nervous system, highlighting important implications for human and animal health.

False HbA1cValue due to a Rare Variant of Hemoglobin J-Cubujuqui.

BACKGROUND: Hemoglobin (Hb) J-Cubujuqui is a rare Hb variant, and reports about it are very limited. There are no descriptions that it affects the results of glycated Hb. METHODS: In this study, we describe a rare variant discovered during newborn screening. Both high-performance liquid chromatography (HPLC) and capillary electrophoresis for hemoglobin analysis displayed abnormal peaks. The Hb variant was confirmed by Sanger sequencing. RESULTS: The pedigree study shows the variant was inherited from the newborn's father. His fasting blood glucose (FBG) level was 5.5 mmol/L. HbA1c measured by HPLC was falsely low in her father (2.41%), whereas that measured by immunoassay was normal (5.11%). Sanger sequencing revealed a heterozygous mutation (CGT˃AGT) at amino acid position 141 of the α1 gene, corresponding to Hb J-Cubujuqui [α1 141(HC3) Arg→Ser (CGT˃AGT); HBA1:c.424C˃A (or HBA2)]. CONCLUSIONS: This is the first report that Hb J-Cubujuqui interferes with the measurement of HbA1cand prompts clinicians to pay attention to the accuracy of glycated Hb results.

Irregular Scene Text Detection Based on a Graph Convolutional Network.

Detecting irregular or arbitrary shape text in natural scene images is a challenging task that has recently attracted considerable attention from research communities. However, limited by the CNN receptive field, these methods cannot directly capture relations between distant component regions by local convolutional operators. In this paper, we propose a novel method that can effectively and robustly detect irregular text in natural scene images. First, we employ a fully convolutional network architecture based on VGG16_BN to generate text components via the estimated character center points, which can ensure a high text component detection recall rate and fewer noncharacter text components. Second, text line grouping is treated as a problem of inferring the adjacency relations of text components with a graph convolution network (GCN). Finally, to evaluate our algorithm, we compare it with other existing algorithms by performing experiments on three public datasets: ICDAR2013, CTW-1500 and MSRA-TD500. The results show that the proposed method handles irregular scene text well and that it achieves promising results on these three public datasets.

Off-label uses of ustekinumab.

Ustekinumab (brand name Stelara®) is a human interleukin-12 and -23 antagonist and has been indicated for the treatments of moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. This review aims to synthesize and interpret the literature evaluating the off-label uses of ustekinumab. We performed searches in PubMed and ClinicalTrials.gov for clinical trials, observational studies, case series, and case reports evaluating label uses of ustekinumab. Studies evaluated the efficacy of ustekinumab for the following conditions: other types of psoriasis (expect plaque psoriasis and psoriatic arthritis), pityriasis rubra pilaris, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, et al. Based on the available literature, ustekinumab appears to be a potential treatment choice for many other diseases. However, more clinical trials data are needed to adequately assess the safety and efficacy of ustekinumab for the treatment of these conditions.

Hb Laibin [ß96(FG3)Leu→Arg; HBB: c.290T>G]: A Novel Hemoglobin Variant Described in a Chinese Family.

We report a novel ß chain hemoglobin (Hb) variant found in a Chinese family. A high level of Hb F was observed on capillary electrophoresis (CE). However, high performance liquid chromatography (HPLC) showed a high level of Hb A2. DNA sequencing revealed a single base substitution (T>G) at codon 96 of exon 2 of the ß-globin gene. This alters the normally encoded leucine to arginine [ß96(FG3)Leu→Arg; HBB: c.290T>G] that we propose to name Hb Laibin for the region of origin of the proband. The pedigree study showed that it was inherited from his mother.

Compound Heterozygosity for a Novel Mutation Codon 104 (-A) (HBB: c.313delA) and Codons 41/42 (-CTTT) (HBB: c.126_129delCTTT) Leading to ß-Thalassemia Major in a Chinese Family.

ß-Thalassemia (ß-thal) is a hereditary blood disorder characterized by the reduced or absent synthesis of ß-globin chains. Here, we report a case of severe thalassemia with compound heterozygosity for a novel deletion mutation at codon 104 (-A) (HBB: c.313delA) and codons 41/42 (-CTTT) (HBB: c.126_129delCTTT) on the ß-globin gene (HBB), and a coinheritance of the -α4.2 (leftward) deletion on the α-globin gene cluster. The proband was a 12-year-old boy, and four other family members were involved in this study. This novel frameshift mutation caused classical ß-thal trait in the heterozygote and a transfusion-dependent form of ß-thal major (ß-TM) in compound heterozygosity with other ß0 mutations.

Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis.

The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model of beta cell ablation, we demonstrate conserved plasticity of alpha cells during islet regeneration. In addition, we show that glucagon expression is upregulated after injury. Through gene knockdown and rescue approaches, we also find that peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate switching. Importantly, whereas beta cell neogenesis was stimulated by glucose, alpha-to-beta cell conversion was not, suggesting that transdifferentiation is not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall, this study supports the hypothesis that alpha cells are an endogenous reservoir of potential new beta cells. It further reveals that glucagon plays an important role in maintaining endocrine cell homeostasis through feedback mechanisms that govern cell fate stability.

Influence of Huang Lian Jie Du Decoction on Quorum Sensing System of Pseudomonas aeruginosa.

Context • Pseudomonas aeruginosa (P aeruginosa) is an opportunistic and nosocomial, Gram-negative pathogen that is characteristic of quorum sensing (QS) modulation. QS inhibition (QSI) is considered to be a new approach to antimicrobial treatment that may reduce issues of antibiotic resistance. Traditional Chinese herbs have been recognized as a source of QSI. Objective • This study was intended to investigate whether the Huang Lian Jie Du decoction (HLJJD) possesses the ability to produce anti-QS activity. Design • P aeruginosa PAO1 was cultivated in the presence and absence of HLJDD or of the aqueous extracts of each of its 4 constituent herbs: Rhizoma coptidis (RC), Radix scutellariae (RS), Cortex phellodendri (CP), and Fructus gardeniae jasminoidis (FGJ). The minimum inhibitory concentrations (MICs) were found for the HLJDD or its 4 constituents through testing each for evidence of antibacterial activity at 3.13, 6.25, 2.5, 25, 50, 100, 200, and 400 mg/mL. Outcome Measures • QS-dependent virulence factors were analyzed at subminimum MICs (sub-MICs) for the HLJDD and its constituent herbs. The mRNA of the QS genes was also assessed by a quantitative real-time polymerase chain reaction. Results • The HLJDD exhibited the lowest MIC of 100 mg/mL, compared with MICs of 200 mg/mL for the RC and RS, 400 mg/mL for the CP, and more than 400 mg/mL for the FGJ. At the sub-MIC of 50 mg/mL for HLJDD, the results showed a significant reduction in pyocyanin pigment, elastolytic activity, proteolytic activity, biofilm formation, and bacterial motilities in the PAO1, without inhibiting the bacterial growth. The mRNA level of the P aeruginosa elastase gene (lasB) was also significantly reduced. The mRNA analysis also showed an increasing tendency for overexpressed QS genes when observed at sub-MICs. That inhibitory tendency was also observed in the sub-MICs of the constituent herbs in different degrees. Conclusions • The HLJDD showed the synergism of its 4 constituents against the growth of P aeruginosa and the QS-dependent virulence factors. Its anti-QS activity may interrupt the QS domination of the virulence factors of P aeruginosa downstream, leading to the overexpressed QS genes.

An insulin signaling feedback loop regulates pancreas progenitor cell differentiation during islet development and regeneration.

As one of the key nutrient sensors, insulin signaling plays an important role in integrating environmental energy cues with organism growth. In adult organisms, relative insufficiency of insulin signaling induces compensatory expansion of insulin-secreting pancreatic beta (ß) cells. However, little is known about how insulin signaling feedback might influence neogenesis of ß cells during embryonic development. Using genetic approaches and a unique cell transplantation system in developing zebrafish, we have uncovered a novel role for insulin signaling in the negative regulation of pancreatic progenitor cell differentiation. Blocking insulin signaling in the pancreatic progenitors hastened the expression of the essential ß cell genes insulin and pdx1, and promoted ß cell fate at the expense of alpha cell fate. In addition, loss of insulin signaling promoted ß cell regeneration and destabilization of alpha cell character. These data indicate that insulin signaling constitutes a tunable mechanism for ß cell compensatory plasticity during early development. Moreover, using a novel blastomere-to-larva transplantation strategy, we found that loss of insulin signaling in endoderm-committed blastomeres drove their differentiation into ß cells. Furthermore, the extent of this differentiation was dependent on the function of the ß cell mass in the host. Altogether, our results indicate that modulation of insulin signaling will be crucial for the development of ß cell restoration therapies for diabetics; further clarification of the mechanisms of insulin signaling in ß cell progenitors will reveal therapeutic targets for both in vivo and in vitro ß cell generation.

Hepatocyte growth factor signaling in intrapancreatic ductal cells drives pancreatic morphogenesis.

In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908) , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF) tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.

Detection of the Unstable Hb Köln (HBB: c.295G>A) by a Capillary Electrophoresis Method.

Hb Köln (HBB: c.295G>A) is an unstable ß-globin gene variant with a GTG>ATG substitution at codon 98. This variant is quite frequent in Europe and the USA but rare in China. It can easily be misdiagnosed as Hb Constant Spring (Hb CS; HBA2: c.427T>C) by high performance liquid chromatography (HPLC), but detection and quantification of both Hb Köln and degraded Hb Köln by capillary electrophoresis (CE) are possible. Thus, we concluded that CE was the preferred method for Hb Köln detection.

Hb Matera (HBB: c.167 T > A): A Second Case Detected in a Pregnant Chinese Woman by the Capillary Electrophoresis Method.

Hb Matera (HBB: c.167 T > A) is an unstable ß-globin gene variant with an ATG > AAG substitution at codon 55. Its coelution with Hb A2 on high performance liquid chromatography (HPLC) makes it difficult to discriminate between Hb Matera and Hb E (HBB: c.79 G > A) that also coelutes with Hb A2 in this method. However, we found that capillary electrophoresis (CE) was able to detect Hb Matera and discriminate it from Hb E, based on the quantification of the peaks and on hematological parameters.

Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.

Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.

Enantioselective organocatalytic oxa-Michael addition of oximes to ß-CF3-ß-disubstituted nitroalkenes: efficient synthesis of ß-amino-α-trifluoromethyl alcohols.

An enantioselective oxa-Michael addition of oximes to ß-CF3-ß-disubstituted nitroalkenes catalyzed by a chiral bifunctional cinchona alkaloid-based thiourea has been developed. A variety of trifluoromethylated oxime ethers possessing a tetrasubstituted carbon stereocenter were obtained in good yields with high enantioselectivities.

A method for extracting buildings from remote sensing images based on 3DJA-UNet3.

Building extraction aims to extract building pixels from remote sensing imagery, which plays a significant role in urban planning, dynamic urban monitoring, and many other applications. UNet3+ is widely applied in building extraction from remote sensing images. However, it still faces issues such as low segmentation accuracy, imprecise boundary delineation, and the complexity of network models. Therefore, based on the UNet3+ model, this paper proposes a 3D Joint Attention (3DJA) module that effectively enhances the correlation between local and global features, obtaining more accurate object semantic information and enhancing feature representation. The 3DJA module models semantic interdependence in the vertical and horizontal dimensions to obtain feature map spatial encoding information, as well as in the channel dimensions to increase the correlation between dependent channel graphs. In addition, a bottleneck module is constructed to reduce the number of network parameters and improve model training efficiency. Many experiments are conducted on publicly accessible WHU,INRIA and Massachusetts building dataset, and the benchmarks, BOMSC-Net, CVNet, SCA-Net, SPCL-Net, ACMFNet, MFCF-Net models are selected for comparison with the 3DJA-UNet3+ model proposed in this paper. The experimental results show that 3DJA-UNet3+ achieves competitive results in three evaluation indicators: overall accuracy, mean intersection over union, and F1-score. The code will be available at https://github.com/EnjiLi/3DJA-UNet3Plus .

The evolution and impact of sarcopenia in severe aplastic anaemia survivors following allogeneic haematopoietic cell transplantation.

BACKGROUND: Sarcopenia is a potential risk factor for adverse outcomes in haematopoietic cell transplantation (HSCT) recipients. We aimed to explore longitudinal body changes in muscle and adipose mass and their prognostic value in allogeneic HSCT-treated severe aplastic anaemia (SAA) patients. METHODS: We retrospectively analysed consecutive SAA patients who underwent allogeneic HSCT between January 2017 and March 2022. Measurements of pectoral muscle and corresponding subcutaneous fat mass were obtained via chest computed tomography at baseline and at 1 month, 3 months, 6 months, and 12 months following HSCT. Sarcopenia was defined as pectoral muscle index (PMI) lower than the sex-specific median at baseline. Changes in body composition over time were evaluated by generalized estimating equations. Cox regression models were used to investigate prognostic factors affecting overall survival (OS) and failure-free survival (FFS). A nomogram was constructed from the Cox regression model for OS. RESULTS: We included 298 adult SAA patients (including 129 females and 169 males) with a median age of 31 years [interquartile range (IQR), 24-39 years] at baseline. Sarcopenia was present in 148 (148/298, 50%) patients at baseline, 218 (218/285, 76%) patients post-1 month, 209 (209/262, 80%) patients post-3 month, 169 (169/218, 78%) patients post-6 month, and 129 (129/181, 71%) patients post-12 month. A significant decrease in pectoral muscle mass was observed in SAA patients from the time of transplant to 1 year after HSCT, and the greatest reduction occurred in post 1-3 months (P < 0.001). The sarcopenia group exhibited significantly lower 5-year OS (90.6% vs. 100%, log-rank P = 0.039) and 5-year FFS (89.2% vs. 100%, log-rank P = 0.021) than the nonsarcopenia group at baseline. Sarcopenia at baseline (hazard ratio, HR, 6.344; 95% confidence interval, CI: 1.570-25.538; P = 0.01; and HR, 3.275; 95% CI: 1.159-9.252; P = 0.025, respectively) and the delta value of the PMI at 6 months post-transplantation (ΔPMI6) (HR, 0.531; 95% CI: 0.374-0.756; P < 0.001; and HR, 0.666; 95% CI: 0.505-0.879; P = 0.004, respectively) were demonstrated to be independent prognostic factors for OS and FFS in SAA patients undergoing HSCT, and were used to construct the nomogram. The C-index of the nomogram was 0.75, and the calibration plot showed good agreement between the predictions made by the nomogram and actual observations. CONCLUSIONS: Sarcopenia persists in SAA patients from the time of transplant to the 1-year follow-up after HSCT. Both sarcopenia at baseline and at 6 months following HSCT are associated with poor clinical outcomes, especially in patients with persistent muscle mass loss up to 6 months after transplantation.

A clinical update of compound heterozygosity for hemoglobin Hekinan II [a27(B8)Glu-Asp; HBA1: c.84G>T] variant in China.

BACKGROUND: Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. METHODS: A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. RESULTS: Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. CONCLUSION: Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.

Exploring the pharmacological mechanism of Tripterygium wilfordii hook for treatment of Behcet's disease using network pharmacology and molecular docking.

Tripterygium wilfordii hook (TWH) has been used to treat Behcet's disease (BD) but its underlying mechanism remains unclear. This study aims to explore the mechanism of TWH on BD using network pharmacology and molecular docking. The bioactive constituents of TWH and their corresponding target genes were extracted from the Traditional Chinese Medicine systems pharmacology database and analysis platform. BD target genes were obtained by searching the DisGeNet and GeneCards databases. Gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were conducted to elucidate the function of overlapping genes between TWH and BD target genes. A protein-protein interaction network was constructed using Cytoscape and STRING platforms, and the core target genes were identified from the overlapping genes. Finally, molecular docking was used to assess the binding affinity between the core targets and TWH bioactive constituents. We identified 25 intersection genes related to both TWH and BD and 27 bioactive ingredients of TWH. Through analysis of protein-protein interaction network, 6 core targets (TNF, IFNG, prostaglandin-endoperoxide synthase 2, NOS2, VCAM-1, and interleukin-2) were screened out. Enrichment analysis demonstrated that the antioxidant properties of TWH constituents might play a significant role in their therapeutic effects. Molecular docking revealed high binding affinity between the bioactive constituents of TWH, such as kaempferol, triptolide, 5, 8-Dihydroxy-7-(4-hydroxy-5-methyl-coumarin-3)-coumarin, and their corresponding target genes, suggesting the potential of TWH to treat BD. Our investigation clarified the active components, therapeutic targets of BD in the treatment of TWH and provided a theoretical foundation for further researches.

Gut microbiota promotes enteroendocrine cell maturation and mitochondrial function.

The enteroendocrine cells (EECs) in the intestine are crucial for sensing ingested nutrients and regulating feeding behavior. The means by which gut microbiota regulates the nutrient-sensing EEC activity is unclear. Our transcriptomic analysis of the EECs from germ-free (GF) and conventionalized (CV) zebrafish revealed that commensal microbiota colonization significantly increased the expression of many genes that are associated with mitochondrial function. Using in vivo imaging and 3D automated cell tracking approach, we developed new methods to image and analyze the EECs' cytoplasmic and mitochondrial calcium activity at cellular resolution in live zebrafish. Our data revealed that during the development, shortly after gut microbiota colonization, EECs briefly increased cytoplasm and mitochondrial Ca2+, a phenomenon we referred to as "EEC awakening". Following the EEC awakening, cytoplasmic Ca2+ levels but not mitochondrial Ca2+ level in the EECs decreased, resulting in a consistent increase in the mitochondrial-to-cytoplasmic Ca2+ ratio. The increased mitochondrial-to-cytoplasmic Ca2+ ratio is associated with the EEC maturation process. In immature EECs, we further discovered that their mitochondria are evenly distributed in the cytoplasm. When EECs mature, their mitochondria are highly localized in the basal lateral membrane where EEC vesicle secretion occurs. Furthermore, CV EECs, but not GF EECs, exhibit spontaneous low-amplitude calcium fluctuation. The mitochondrial-to-cytoplasm Ca2+ ratio is significantly higher in CV EECs. When stimulating the CV zebrafish with nutrients like fatty acids, nutrient stimulants increase cytoplasmic Ca2+ in a subset of EECs and promote a sustained mitochondrial Ca2+ increase. However, the nutrient induced EEC mitochondrial activation is nearly abolished in GF zebrafish. Together, our study reveals that commensal microbiota are critical in supporting EEC mitochondrial function and maturation. Selectively manipulating gut microbial signals to alter EEC mitochondrial function will provide new opportunities to change gut-brain nutrient sensing efficiency and feeding behavior.