Abstract Pregnancy is accompanied by profound endocrine remodeling, yet the mechanisms by which maternal hormonal signals establish long-term tissue homeostasis remain largely unknown. Here we identify maternal progesterone signaling as a developmental cue that establishes lifelong oral homeostasis through a hormone–lipid–microbiome axis. We show that the membrane progesterone receptor mPRδ is selectively expressed in the developing and maternal submandibular glands, where it mediates non-genomic progesterone signaling to promote epithelial differentiation by driving the selective mobilization of docosahexaenoic acid (DHA). Loss of this pathway disrupts salivary gland maturation, reshapes the oral microbial ecosystem through the selective expansion of Pasteurellaceae, and causes local inflammation as well as systemic metabolic dysfunction. Mechanistically, antibiotic treatment abolishes these phenotypes, whereas transfer of the oral microbiota recapitulates disease, demonstrating that developmental defects in the host are translated into long-term pathology through the oral microbiome. Remarkably, maternal—but not adult—DHA supplementation restores salivary gland development and microbial homeostasis and prevents adult disease phenotypes, identifying a critical developmental window during which oral homeostasis is durably established. Collectively, these findings reveal a previously unrecognized maternal endocrine mechanism that establishes lifelong host–microbiome homeostasis and identify developmental programming as a fundamental principle linking maternal physiology to adult health. Abstract Figure

The endocannabinoid (EC) system in the central and peripheral nerves plays a crucial role in various physiological processes, including feeding behaviour and energy metabolism. In particular, gut ECs stimulate appetite, and excessive activation of the system can induce hedonic eating, leading to obesity. Previous studies have indicated elevation of gut EC levels in high-fat diet-induced or genetically obese rodents. The present study aimed to expand our understanding of gut ECs involved in feeding behaviour during obesity by characterising the profiles of arachidonic metabolites, including ECs, in the gut and by examining their impact on feeding behaviour in KK-A y mice, an obesity model established by crossing diabetic KK mice with lethal yellow (A y ) mice. KK-A y mice exhibit hyperphagia compared with lean mice under either free-feeding condition or refeeding condition after 24 h of food deprivation. Meal pattern analyses revealed that hyperphagia in KK-A y mice was primarily due to higher meal frequency rather than meal size or interval, suggesting a defect in hunger control. In addition, levels of EC and other arachidonic acid metabolites such as prostaglandin E2 and F2α were elevated in KK-A y mice. Pharmacological blockade of the peripheral cannabinoid receptor 1 (CB1) and diacylglycerol lipase, but not N-acyl phosphatidylethanolamine phospholipase D, reduced food intake, as did treatment with cyclo-oxygenase-2 inhibitors. These findings suggest that intestinal 2-arachidonoyl glycerol-dependent CB1 activation contributes to hyperphagic behaviour in KK-A y mice and PGs are involved in feeding control.

We aimed to elucidate the dynamic changes in short-chain fatty acids (SCFA) produced by the gut microbiota following smoking exposure and their role in chronic obstructive pulmonary disease (COPD) pathogenesis. SCFA concentrations were measured in human plasma, comparing non-smokers (n = 6) and smokers (n = 12). Using a mouse COPD model induced by cigarette smoke exposure or elastase-induced emphysema, we modulated SCFA levels through dietary interventions and antibiotics to evaluate their effects on inflammation and alveolar destruction. Human smokers showed lower plasma SCFA concentrations than non-smokers, with plasma propionic acid positively correlating with forced expiratory volume in 1 s/forced vital capacity. Three-month smoking-exposed mice demonstrated altered gut microbiota and significantly reduced fecal SCFA concentrations compared to air-exposed controls. In these mice, a high-fiber diet increased fecal SCFAs and mitigated inflammation and alveolar destruction, while antibiotics decreased fecal SCFAs and exacerbated disease features. However, in the elastase-induced model, fecal SCFA concentration remained unchanged, and high-fiber diet or antibiotic interventions had no significant effect. These findings suggest that smoking exposure alters gut microbiota and SCFA production through its systemic effects. The anti-inflammatory properties of SCFAs may play a role in COPD pathogenesis, highlighting their potential as therapeutic targets.

Although impaired intestinal barrier function is implicated in type 2 diabetes (T2D), its direct in vivo assessment in humans remains challenging, limiting our understanding of the underlying mechanisms. We utilized a novel endoscopic real-time, in situ impedance measurement technique to investigate how hyperglycemia and the intestinal microbiota contribute to intestinal barrier dysfunction in T2D. We validated this impedance-based approach against ex vivo transepithelial electrical resistance (TEER) (r = 0.64, p = 0.011) and applied it to 137 patients undergoing colonoscopy. A mechanistic study (22 T2D, 19 controls) analyzed mucosal microbiota, short-chain fatty acid (SCFA) levels, and tight junction protein gene expression. In vitro assays with Caco-2 monolayers evaluated Bacteroides vulgatus (B. vulgatus) supernatant and high-glucose exposure effects on TEER. Patients with T2D had significantly lower ileal impedance (20.9 Ω·cm2) compared to controls (24.2 Ω·cm2; p < 0.001). Lower Bacteroides abundance correlated with decreased SCFA biosynthesis gene expression and ZO-1 levels. B. vulgatus supernatant counteracted lipopolysaccharide-induced barrier disruption. High-glucose exposure reduced transepithelial electrical resistance (p < 0.05), indicating a direct detrimental effect. Impedance negatively correlated with HbA1c (r = − 0.49, p < 0.001), and metformin use was associated with preserved barrier function. To our knowledge, this study provides the first direct, in situ evidence that intestinal barrier function is impaired in T2D, a condition associated with concurrent microbial and metabolic alterations. Our findings establish intestinal barrier dysfunction as a key pathophysiological feature of T2D, suggesting that interventions aimed at the intestinal barrier function may represent a novel therapeutic strategy.

Water-soluble cellulose acetate (WSCA), derived from natural cellulose and acetate, can be used as a food additive and deliver acetate to the large intestine. In this study, we investigated the effects of dietary WSCA supplementation on impaired glucose metabolism in db/db mice, a model of type 2 diabetes mellitus. db/m and db/db mice were fed either a control diet or a WSCA-supplemented diet for eight weeks. The WSCA-supplemented group exhibited improved glucose intolerance or lipid metabolism without any loss of skeletal muscle mass or grip strength. WSCA supplementation significantly increased acetate concentrations in the cecum, stool, and blood. Furthermore, serum levels of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were significantly higher in the WSCA group than in the control group. These findings suggest that WSCA delivers acetate to the colon and prevents diabetes by enhancing GLP-1 and PYY secretion in db/db mice.

Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S. salivarius may prevent host obesity caused by excess sucrose intake via the exopolysaccharide (EPS) –short-chain fatty acid (SCFA) –carbohydrate metabolic axis in male mice. Healthy human donor-derived S. salivarius produced high EPS levels from sucrose but not from other sugars. S. salivarius abundance was significantly decreased in human donors with obesity compared with that in healthy donors, and the EPS–SCFA bacterial carbohydrate metabolic process was attenuated. Our findings reveal an important mechanism by which host–commensal interactions in glycometabolism affect energy regulation, suggesting an approach for preventing lifestyle-related diseases via prebiotics and probiotics by targeting bacteria and EPS metabolites. While diet is essential for daily nutrient acquisition, excessive intake of sugar-rich foods drives obesity and related health issues like diabetes. Here, the authors show that commensal bacterium S. salivarius curbs obesity by transforming dietary sugars into beneficial compounds.

Abstract GPR164 is a free fatty acid receptor, activated by both short-chain fatty acids and medium-chain fatty acids, and expressed throughout the gastrointestinal tract. Although GPR164 is reported to be involved in the release of gut hormones, the physiological functions of this receptor in the maintenance of intestinal homeostasis remain unclear. In this study, we explore the role of GPR164 in regulating intestinal barrier function using mice lacking Gpr164 gene (Gpr164 −/−). A loss-of-function mutation in Gpr164 promotes cell proliferation and disrupts the intestinal barrier function in both Caco-2 cells and mice. Genome-wide RNA-seq analysis reveals that Gpr164 deletion causes aberrant Wnt/β-catenin signaling, and the intraperitoneal injection of the Wnt/β-catenin inhibitor PNU-74654 ameliorates intestinal hyperproliferation, differentiation and barrier permeability phenotypes of Gpr164 −/− mice. Gpr164 −/− mice also exhibit gut microbial dysbiosis and inflammation. Thus, our findings uncover the pivotal role of GPR164 in the maintenance of intestinal homeostasis through regulating barrier function.

The ketogenic diet (KD) promotes ketone body synthesis and has been used therapeutically for over a century. The therapeutic efficacy of the KD is largely attributed to ketone bodies, β-hydroxybutyrate (βHB), and acetoacetate. GPR109A, the receptor for βHB, has been shown to regulate immune responses, but its role in metabolism remains unclear. This study investigated the role of GPR109A in lipid metabolism under specific ketogenic conditions, such as fasting and KD feeding. Gpr109a-/- mice exhibited increased hepatic lipid accumulation, inflammation, and fibrosis after being fed the KD, indicating that GPR109A, highly expressed in macrophages, modulates macrophage-driven inflammation and thus has a protective role in the liver. In contrast, GPR109A did not contribute to hepatic protection during short-term fasting, suggesting that its role is more pronounced under specific ketogenic conditions. Further analysis of this mechanism revealed that GPR109A protects the liver from inflammation by maintaining intestinal barrier integrity and limiting lipopolysaccharide (LPS) leakage from the gut under diet-induced ketogenic conditions. These findings highlight the novel protective mechanism of GPR109A, via the gut-liver axis, to sustain metabolic homeostasis during the KD. This study provides valuable insights into the physiological effects of ketone bodies. ARTICLE HILIGHTS ### Competing Interest Statement The authors have declared no competing interest. * BDH1 : D-β-Hydroxybutyrate Dehydrogenase 1 cDNA : Complementary DNA DCs : Dendritic Cells EDTA : Ethylenediaminetetraacetic Acid FFAR : Free Fatty Acid Receptor HMG-CoA : 3-Hydroxy-3-Methylglutaryl-CoA HMGCS2 : 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 HMGCL : 3-Hydroxy-3-Methylglutaryl-CoA Lyase HCAR : Hydroxycarboxylic Acid Receptor IL-10 : Interleukin 10 KD : Ketogenic Diet LC-MS/MS : Liquid Chromatography-Mass Spectrometry/Mass Spectrometry LDL-C : Low-Density Lipoprotein Cholesterol LCT : Long-Chain Triglyceride MCT : Medium-Chain Triglyceride NEAA : Non-Essential Amino Acid NEFA : Non-Esterified Fatty Acid ND : Normal Diet SCOT : Succinyl-CoA:3-Ketoacid CoA Transferase TG : Triglyceride JSPS, JP25H01097, JP22KJ1973 JST, JPMJMS2023 Oil & Fat Industry Kaikan Gunma University

BACKGROUND:Gut microbiota are known to mediate human health and are affected by physiological conditions, including hypoxia. Although studies involving animal models have shown that intermittent hypoxia alters gut microbiota, its effects in adult Japanese patients with obstructive sleep apnoea (OSA) remain unclear. We investigated the association between OSA severity and gut microbiota composition in Japanese adults with OSA. METHODS:This cross-sectional study included 74 Japanese diagnosed with OSA via polysomnography. The average body mass index was 30.5 ± 3.8 kg/m2 and the average 3 % oxygen desaturation index (ODI) was 39.9 ± 20.0. No control group was included. Faecal samples were collected in a fasting period of >10 h. The association between 3 % ODI and gut microbiota were analysed at the phylum, family and genus level. RESULTS:At the phylum level, 3 % ODI significantly positively correlated with Actinobacteria (r = 0.3151, p = 0.0126) and negatively correlated with Firmicutes (r = -0.3150, p = 0.0126). No significant correlations were found with Proteobacteria or Bacteroidetes. At the family level, 3 % ODI significantly positively correlated with Bifidobacteriaceae in Actinobacteria (r = 0.2373, p = 0.0418). At genus level, Bifdobacterium was prominently increased compared with other group. CONCLUSION:This study showed that the gut microbiome in Japanese with OSA showed an increase in Bifdobacterium. Although our cohort was biased towards moderate obesity and severe OSA severity, intermittent hypoxia might contribute to the change of gut microbiome. These findings suggest that increased Bifdobacterium may help maintain gut homeostasis under hypoxic stress, especially in Japanese.

AIM:Gut microbiota dysbiosis causes atherosclerosis. Patients with atherosclerosis and type 2 diabetes mellitus (T2D) often have low Bacteroides abundance, potentially increasing atherosclerosis risk. This study investigated the association between low Bacteroides abundance and endothelial dysfunction in patients with T2D. METHODS:The relationship between the relative Bacteroides abundance in fecal gut microbiota, assessed by 16S ribosomal RNA analysis, and the reactive hyperemia index (RHI) was investigated in 93 patients with T2D (68 men and 25 women). Clinical parameters, including plasma short-chain fatty acids and inflammatory markers, were also examined. Heatmap analysis compared lower Bacteroides group vs. upper Bacteroides group. RESULTS:Natural log-transformed RHI (Ln-RHI) was positively correlated with Ln-relative Bacteroides abundance (p < 0.05). The low Bacteroides group had a considerably lower Ln-RHI than the high group (p = 0.038). Plasma acetate content was correlated with relative Bacteroides abundance (p = 0.036) but not with Ln-RHI content. The low Bacteroides group tended to have higher high-sensitivity C-reactive protein levels than the high group (p = 0.069). No other bacterial differences between the groups were associated with the RHI. CONCLUSIONS:Low Bacteroides abundance is associated with low RHI and may be associated with the risk of atherosclerosis in patients with T2D.

Eosinophils are major effector cells in type 2 immune responses, contributing to host defense and allergic diseases. They also contribute to maintaining tissue homeostasis by regulating various immune cell types, including neutrophils. Here we show that eosinophils directly associate with neutrophils in the lungs of asthma-induced mice. Eosinophil-specific deficiency of the short-chain fatty acid receptor, GPR43, results in hyperactivation of eosinophils and increases the expression of neutrophil chemoattractants and PECAM-1, thereby enhancing the interaction between eosinophils and neutrophils. This interaction exposes neutrophils to eosinophil-derived IL-4 and GM-CSF, which induce the conversion of conventional neutrophils into more pathogenic, Siglec-Fhi neutrophils capable of enhancing Th17 cell differentiation and aggravating asthma symptoms in mouse models. Our results thus implicate GPR43 as a critical regulator of eosinophils, and describe eosinophil-mediated modulation of neutrophil differentiation and function.

Sda antigens [GalNAcβ1-4(Neu5Acα2-3)Galβ1-O-R] are present at the nonreducing termini of O-glycans of colonic mucins of humans. Previously, we reported characterization of two glycoside hydrolase (GH) family 33 α-sialidases, SiaBb1 and SiaBb2, from a symbiotic Bifidobacterium bifidum dwelling in the human intestines. In this study, we identified a third α-sialidase, SiaBb3 from B. bifidum, that is distinguished from the aforementioned two sialidases by its possession of an additional GH123 β-N-acetylgalactosaminidase domain within the same polypeptide. The purified recombinant SiaBb3 efficiently converted GM2 ganglioside [GalNAcβ1-4(Neu5Acα2-3)Galβ1-4Glcβ1-ceramide], sharing the same terminal trisaccharide structure with the Sda antigen, to lactosylceramide by releasing Neu5Ac and GalNAc in the presence of 0.1% sodium cholate. Hydrolysis of the GM2 oligosaccharide proceeds with the initial release of Neu5Ac, followed by the liberation of GalNAc, which was revealed by monitoring the reactions performed using catalytically inactive mutants for each domain of SiaBb3 and by analyzing the reactions of WT SiaBb3 on fluorescence-labeled oligosaccharides. Notably, the order of hydrolysis was reversed compared with that employed by mammalian lysosomal enzymes for GM2 degradation. Comparative O-glycomic analysis using fecal mucin as a substrate unequivocally demonstrated that SiaBb3 targets the Sda antigen of mucin O-glycans. The GH33-inactive SiaBb3 mutant retained Sda antigen-containing O-glycans intact, indicating that initial hydrolysis of Neu5Ac is essential for the subsequent removal of GalNAc. Taken together, these results indicate that SiaBb3 is a bifunctional enzyme specialized for the complete degradation of Sda antigens in host mucins.

GPR164 is a novel free fatty acid receptor, activated by both short-chain fatty acids and medium-chain fatty acids, and expressed throughout the gastrointestinal tract. Although GPR164 is reported to be involved in the release of gut hormones, the physiological functions of this receptor in the maintenance of intestinal homeostasis remain unclear. In this study, we explored the role of GPR164 in regulating intestinal barrier function using mice lacking Gpr164 gene (Gpr164-/-). A loss-of-function mutation in GPR164 promoted cell proliferation and disrupted the intestinal barrier function in both Caco-2 cell line and mice. Genome-wide RNA-seq analysis revealed that GPR164 deletion caused aberrant wnt/beta-catenin signaling, and the intraperitoneal injection of wnt/beta-catenin inhibitor ameliorated a series of abnormalities of Gpr164-/- mice. Gpr164-/- mice also exhibited gut microbial dysbiosis and severe inflammation, indicating that deletion of Gpr164 causes similar pathologies observed in patients with inflammation bowel disease (IBD). Thus, our findings uncover the pivotal role of GPR164 in the maintenance of intestinal barrier function, providing an attractive clinical target for IBD. ### Competing Interest Statement The authors have declared no competing interest.

BackgroundGPR30 is a membrane-associated receptor involved in rapid, non-genomic estrogen signaling. Estrogen significantly influences hair growth and susceptibility to hair loss, with differences primarily driven by hormonal factors. While estrogen’s role in regulating hair follicle cycling is recognized, its precise molecular mechanisms remain unclear. This study investigates the role of GPR30 in hair follicle biology and evaluates its potential as a therapeutic target for estrogen-mediated hair loss disorders.MethodsThe GPR30 selective agonist G-1 was administrated to female Gpr30-deficient mice with a C57BL/6J background and human hair follicle dermal papilla cell, and the effects on hair growth and the molecular signaling were evaluated.ResultsWe demonstrate that GPR30 is abundantly expressed in mouse skin, particularly during the anagen phase of the hair follicle cycle, implicating it in hair growth regulation. Activation of GPR30 using the selective agonist G-1 in mouse skin and human dermal papilla cells significantly upregulated Wnt/Hedgehog signaling, which are key pathways promoting hair growth. These effects were absent in Gpr30-deficient mice or in those administered a GPR30 antagonist, confirming the essential role of GPR30 in estrogen-mediated regulation of hair follicle activity.ConclusionOur findings underscore the importance of GPR30 in modulating hair growth and suggest that GPR30, along with its selective agonists, holds promise as a novel therapeutic target for treating hair loss disorders and other estrogen-responsive conditions.

Obesity is a major healthcare problem worldwide and is induced by excess energy intake, resulting in gut microbial composition and microbial diversity changes. Through fermentation of dietary fibers, short-chain fatty acids (SCFAs) act as host energy sources and signaling molecules via G protein-coupled receptors such as GPR41. Acidipropionibacterium acidipropionici is widely used in many applications; however, in vivo studies on the beneficial effect of A. acidipropionici via propionate production and host energy homeostasis are unclear. Therefore, this study aimed to investigate the beneficial metabolic effects of A. acidipropionici by focusing on GPR41 signaling in a high-fat diet (HFD)-induced obesity mouse model. Here, we demonstrated that A. acidipropionici OB7439 improved host metabolism in HFD-induced obesity in mice. The intake of A. acidipropionici OB7439 improved metabolism in HFD-induced obese mice by increasing propionate production, regulating glucose tolerance, and inhibiting hepatic inflammation via GPR41 signaling. Our findings shed light on the potential of using A. acidipropionici OB7439 as an SCFA producer for the prevention and treatment of metabolic disorders. Based on these results, we suggest that A. acidipropionici may be a potential therapeutic bacterium that inhibits obesity and modulates the gut microbial community.

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPRε) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPRε by increased progesterone during pregnancy enhances maternal insulin resistance via prostaglandin production, efficiently providing glucose to embryos. Correspondingly, the offspring of mPRε-deficient mothers exhibited metabolic dysfunction, whereas mPRε-deficient mothers with high-fat diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo. Additionally, mPRε may represent a modulator for treating pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring.

Soy isoflavones are involved deeply in our diet as beneficial to health. It is known to have anti-inflammatory and antioxidant effects and also to be effective in alleviating various lifestyle diseases, as well as the maintenance of endocrine function, especially with age-related diseases such as osteoporosis. Here we investigated the impact of age-dependent changes with the intestinal microbiota in physiologically aged C57BL/6 N by free drinking water with soluble soybean-derived isoflavone glycosides (SIFs) for 4 weeks. Consequently, Akkermansia muciniphila (A. muciniphila) species represented an age-dependent increase with SIF treatment, subsequently, generally age-dependent decreased goblet cells are retained in the large intestine. These results invoke that SIF plays a beneficial role in intestinal barrier function to maintain large intestine homeostasis. Interestingly, we also revealed that SIF had an alleviating effect on age-dependent bone loss. Taken together, SIF has a fruitful effect on the intestinal environment and the maintenance of homeostasis in physiological aging.

Effective approaches to preventing and treating obesity are urgently needed. Although current strategies primarily focus on direct modulation of host metabolism, another promising approach may involve limiting nutrient availability through regulation of the gut microbiota, which links diet and host physiology. Here, we report that acetylated cellulose (AceCel), which markedly alters gut bacterial composition and function, reduces body mass gain in both wild-type and obese mice. AceCel limits carbohydrate oxidation and promotes fatty acid oxidation in the host liver in a microbiota-dependent manner. We further show that acetate enhances carbohydrate fermentation by the gut commensal Bacteroides thetaiotaomicron, depleting host-accessible simple sugars in the gut of AceCel-fed mice. These findings highlight the potential of AceCel as a prebiotic that regulates carbohydrate metabolism in both bacteria and host, offering promise as a therapeutic strategy for obesity.

Background: Overweight and obesity are currently a worldwide problem, with undesirable health consequences, such as type 2 diabetes. Therefore, much attention has been paid to preventing obesity through diet. Free fatty acids (FFAs) serve as signaling molecules in many biological processes, leading to increased energy expenditure and insulin secretion. Short-chain fatty acids (SCFAs) such as acetic, propionic and butyric acid are bioactive metabolites produced by gut microbes, and their beneficial effects on host metabolism are well studied. However, the effects of hexanoic acid on metabolism are poorly understood. Methods: Male C57BL/6J mice were fed a normal chow diet, a high-fat diet (HFD), an HFD containing 5% butyric acid or an HFD containing 5% hexanoic acid for 4 weeks, and the effects of hexanoic acid on their lipid and glucose metabolisms were examined. Results: Dietary supplementation of hexanoic acid or butyric acid for 4 weeks prevented HFD-induced obesity and fat accumulation in the white adipose tissues. Both FFAs also suppressed the elevated plasma non-esterified fatty acid (NEFA) levels and hepatic triglyceride content in the mice fed an HFD. In addition, butyric acid and hexanoic acid decreased the elevated expression of genes involved in fatty acid biosynthesis in the white adipose tissues under HFD conditions. Hyperinsulinemia induced by HFD feeding was attenuated by oral intake of butyric acid or hexanoic acid, whereas hyperglycemia under HFD feeding was improved only through oral administration of hexanoic acid. Hexanoic acid increased plasma glucagon-like peptide-1 (GLP-1) levels and the expression of genes associated with gluconeogenesis. The intraperitoneal glucose tolerance test (IPGTT) and the insulin tolerance test (ITT) revealed that the oral administration of hexanoic acid significantly enhanced glucose tolerance and insulin sensitivity. Conclusions: This study highlights the importance of hexanoic acid in improving lipid and glucose metabolisms. Hexanoic acid, as well as butyric acid, is a remarkable FFA with anti-obesity properties. Furthermore, hexanoic acid is more potent in maintaining glucose homeostasis than butyric acid. Thus, our findings provide insight into the development of functional foods which could prevent obesity-related diseases such as type 2 diabetes.