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Background: The relationship between gut microbiota composition, lifestyles, and colonic transit time (CTT) remains poorly understood. This study investigated associations among gut microbiota profiles, diet, lifestyles, and CTT in individuals with subjective constipation. Methods: We conducted a secondary analysis of data from our randomized clinical trial, examining gut microbiota composition, CTT, and dietary intake in baseline and final assessments of 94 participants with subjective constipation. Participants were categorized into normal-transit (<36 h) and slow-transit (≥36 h) groups based on CTT at baseline. Gut microbiota composition was measured using 16S rRNA sequencing, and dietary patterns were assessed through semi-quantitative food frequency questionnaires. Enterotype analysis, machine learning approaches, and metabolic modeling were employed to investigate microbiota–diet interactions. The constipated participants primarily belonged to Lachnospiraceae (ET-L). Results: The slow-transit group showed higher alpha diversity than the normal-transit group. Butyricicoccus faecihominis was abundant in the normal-transit group, while Neglectibacter timonensis, Intestinimonas massiliensis, and Intestinibacter bartlettii were abundant in the slow-transit group, which also had a higher abundance of mucin-degrading bacteria. Metabolic modeling predicted increased N-acetyl-D-glucosamine (GlcNAc), a mucin-derived metabolite, in the slow-transit group. Network analysis identified two microbial co-abundance groups (CAG3 and CAG9) significantly associated with transit time and dietary patterns. Six mucin-degrading species showed differential correlations with GlcNAc and a plant-based diet, particularly, including rice, bread, fruits and vegetables, and fermented beans. In conclusion, an increased abundance of mucin-degrading bacteria and their predicted metabolic products were associated with delayed CTT. Conclusion: These findings suggest dietary modulation of these bacterial populations as a potential therapeutic strategy for constipation. Moreover, our results reveal a potential immunometabolic mechanism where mucin-degrading bacteria and their metabolic interactions may influence intestinal transit, mucosal barrier function, and immune response. [ABSTRACT FROM AUTHOR] more...

Background/Objectives: Schisandra chinensis Fructus (SCF) is a traditional medicinal herb containing lignans that improves glucose metabolism by mitigating insulin resistance. We aimed to investigate the therapeutic potential and action mechanism of SCF for Alzheimer's disease (AD) using a network pharmacology analysis, followed by experimental validation in an AD rat model. Methods: The biological activities of SCF's bioactive compounds were assessed through a network pharmacology analysis. An AD rat model was generated by infusing amyloid-β peptide (Aβ) (25–35) into the hippocampus to induce Aβ accumulation. The AD rats were fed either 0.5% dextrin (AD-Con) or 0.5% SCF (AD-SCF group) in a high-fat diet for seven weeks. The rats in the normal/control group received an Aβ (35–25) infusion (no Aβ deposition) and were fed a control diet (Normal-C). Aβ deposition, memory function, inflammation, and glucose/lipid metabolism were evaluated. Results: The network analysis revealed significant intersections between AD-related targets and bioactive SCF compounds, like gomisin A, schisandrin, and longikaurin A. Key AD genes prostaglandin-endoperoxide synthase-2 (PTGS2, cyclooxygenase-2) and acetylcholinesterase (AChE) were linked to SCF compounds. In the rats with AD induced by bilaterally infusing amyloid-β (25–35) into the hippocampus, the 0.5% SCF intake mitigated hippocampal amyloid-β deposition, neuroinflammation, memory deficits, and dysregulated glucose and lipid metabolism versus the AD controls. SCF reduced hippocampal AChE activity, inflammatory cytokine expression related to PTGS2, and malondialdehyde contents and preserved neuronal cell survival-related factors such as brain-derived neurotrophic factor and ciliary neurotrophic factor similar to normal rats. The neuroprotective effects validated the network analysis findings. Conclusions: SCF could be a potential AD therapeutic agent by activating the parasympathetic nervous system to reduce hippocampal oxidative stress and inflammation, warranting further clinical investigations of its efficacy. [ABSTRACT FROM AUTHOR] more...

The vagus nerve regulates metabolic homeostasis and mediates gut–brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut–brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut–brain axis. Targeting the gut–brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke. [ABSTRACT FROM AUTHOR] more...

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is characterized by hepatic fat accumulation by metabolic dysfunction. The rising prevalence of MAFLD, especially among Asians, may be associated with changes in gut microbiota. We investigated gut microbiota characteristics and potential mechanisms leading to MAFLD development according to enterotypes. Case-control studies examining the gut microbiota composition between MAFLD and non-MAFLD participants were searched in public databases until July 2023. Gut microbiota was categorized into two enterotypes by principal component analysis. According to the enterotypes, LEfSe, ALDEx2, XGBoost, and DCiPatho were utilized to identify differential abundances and pathogenic microbes in the gut between the MAFLD and non-MAFLD groups. We analyzed microbial community networks with the SprCC module and predicted microbial functions. In the Prevotella enterotype (ET-P), 98.6% of Asians and 65.1% of Caucasians were associated with MAFLD (p = 0.049). MAFLD incidence was correlated with enterotype, age, obesity, and ethnicity (p < 0.05). Asian MAFLD patients exhibited decreased Firmicutes and Akkermansia muciniphila and increased Bacteroidetes and P. copri. The pathogenicity scores were 0.006 for A. muciniphila and 0.868 for P. copri. The Asian MAFLD group showed decreased stability and complexity in the gut microbiota network. Metagenome function analysis revealed higher fructose metabolism and lipopolysaccharide (LPS) biosynthesis and lower animal proteins and α-linolenic acid metabolism in Asians with MAFLD compared with the non-MAFLD group. LPS biosynthesis was positively correlated with P. copri (p < 0.05). In conclusion, P. copri emerged as a potential microbial biomarker for MAFLD. These findings enhance our understanding of the pathological mechanisms of MAFLD mediated through the gut microbiota, providing insights for future interventions. [ABSTRACT FROM AUTHOR] more...

This study aimed to investigate alterations in the gut microbiota of patients with depression compared to those in the gut microbiota of healthy individuals based on enterotypes as a classification framework. Fecal bacteria FASTA/Q samples from 333 Chinese participants, including 107 healthy individuals (Healthy group) and 226 individuals suffering from depression (DP group), were analyzed. The participants were classified into three enterotypes: Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). An α-diversity analysis revealed no significant differences in microbial diversity between the Healthy and DP groups across all enterotypes. However, there were substantial differences in the gut microbial composition for β-diversity, particularly within ET-L and ET-B. The DP group within ET-B exhibited a higher abundance of Proteobacteria, while a linear discriminant analysis (LDA) of the DP group showed an increased relative abundance of specific genera, such as Mediterraneibacter, Blautia, Bifidobacterium, and Clostridium. Within ET-L, Bifidobacterium, Blautia, Clostridium, Collinsella, and Corynebacterium were significantly higher in the DP group in the LDA and ANOVA-like differential expression-2 (ALDEx2) analyses. At the species level of ET-L, Blautia luti, Blautia provencensis, Blautia glucerasea, Clostridium innocuum, Clostridium porci, and Clostridium leptum were the primary bacteria in the DP group identified using the machine learning approach. A network analysis revealed a more tightly interconnected microbial community within ET-L than within ET-B. This suggests a potentially stronger functional relationship among the gut microbiota in ET-L. The metabolic pathways related to glucose metabolism, tryptophan and tyrosine metabolism, neurotransmitter metabolism, and immune-related functions showed strong negative associations with depression, particularly within ET-L. These findings provide insights into the gut–brain axis and its role in the pathogenesis of depression, thus contributing to our understanding of the underlying mechanisms in Asian individuals. Further research is warranted to explain the mechanistic links between gut microbiota and depression and to explore their potential for use in precision medicine interventions. [ABSTRACT FROM AUTHOR] more...

We investigated the effects of different types of long-term fermented soybeans (traditionally made doenjang; TMD) on glucose and bone metabolism and memory function in ovariectomized (OVX) rats. The rats were categorized into six groups: Control, cooked unfermented soybeans (CSB), and four TMDs based on Bacillus subtilis (B. subtilis) and biogenic amine contents analyzed previously: high B. subtilis (HS) and high biogenic amines (HA; HSHA), low B. subtilis (LS) and HA (LSHA), HS and low biogenic amines (LA; HSLA), and LS and LA (LSLA). The rats in the CSB and TMD groups fed orally had a 4% high-fat diet for 12 weeks. Rats in the Control (OVX rats) and Normal-control (Sham-operated rats) groups did not consume CSB or TMD, although macronutrient contents were the same in all groups. Uterine weight and serum 17β-estradiol concentrations were much lower in the Control than the Normal-control group, but CSB and TMD intake did not alter them regardless of B. subtilis and biogenic amine contents. HOMA-IR, a measure of insulin resistance, decreased with TMD with high B. subtilis (HSLA and HSHA) compared to the Control group. In OGTT and IPGTT, serum glucose concentrations at each time point were higher in the Control than in the Normal-control, and HSLA and HSHA lowered them. Memory function was preserved with HSHA and HSLA administration. Bone mineral density decline measured by DEXA analysis was prevented in the HSHA and HSLA groups. Bone metabolism changes were associated with decreased osteoclastic activity, parathyroid hormone levels, and osteoclastic activity-related parameters. Micro-CT results demonstrated that TMD, especially HSLA and HSHA, preserved bone structure in OVX rats. TMD also modulated the fecal bacterial community, increasing Lactobacillus, Ligalactobacillus, and Bacillus. In conclusion, through gut microbiota modulation, TMD, particularly with high B. subtilis content, acts as a synbiotic to benefit glucose, bone, and memory function in OVX rats. Further research is needed to make specific recommendations for B. subtilis-rich TMD for menopausal women. [ABSTRACT FROM AUTHOR] more...

Traditionally made doenjang (TMD) produced by the long-term fermentation of soybeans with salt may improve symptoms of estrogen deficiency. We aimed to evaluate the effects of four TMD types, containing low and high amounts of Bacillus species and biogenic amines (HBHA, HBLA, LBHA, and LBLA), on energy, glucose, and lipid metabolism, by altering the gut microbiota in estrogen-deficient ovariectomized (OVX) rats. Their mechanisms were also examined. The OVX rats were divided into the control, cooked soybean (CSB), HBHA, LBHA, HBLA, and LBLA groups. Sham-operated rats were the normal control group. Serum 17β-estradiol concentrations were similar among all OVX groups. Tail skin temperatures, which are indicative of hot flashes, were higher in the control than the HBHA and HBLA groups and were similar to the normal control group. Weight gain and visceral fat mass were lower in the TMD and CSB intake groups but not as low as in the normal control group. Lean body mass showed a trend opposite to that of visceral fat in the respective groups. The hepatic triglyceride content decreased with the TMD intake compared to the control and CSB groups. mRNA expressions of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and carnitine palmitoyltransferase-1 in the TMD and CSB groups were as high as in the normal control group, and the PPAR-γ mRNA expression was more elevated in the HBLA group than in the normal control group. The morphology of the intestines improved in the TMD groups compared to the control, and the HBHA and HBLA groups showed an enhanced improvement compared to the CSB group. The HBHA, HBLA, and LBHA groups increased the α-diversity of the cecal microbiota compared to the control. Akkermenia and Lactobacillus were higher in the HBLA and LBLA groups compared to the control. The expression of the estrogen, forkhead box proteins of the class-O subgroup, and insulin-signaling pathways were lower in the control group, and HBHA and HBLA prevented their decrement. In conclusion, long-term treatment with TMD containing high amounts of Bacillus potentially improves estrogen deficiency symptoms more than unfermented soybeans. [ABSTRACT FROM AUTHOR] more...

Simple Summary: The porcine placenta has been traditionally used as a potential treatment for liver damage, and enzymatic porcine placenta hydrolysate (EPPH) may promote efficacy. However, there are few studies of EPPH to demonstrate exercise-induced physical and cognitive fatigue. Daily intake of EPPH rich in glycine, glutamate, arginine, alanine, leucine, lysine, and oligopeptides (0.16–0.31 mL/kg bw; 5 mg nitrogen/mL) alleviates exercise-induced fatigue in an animal model by decreasing fatigue-related metabolite concentrations, including lactate, blood urinary nitrogen, and creatinine, reducing liver damage, and increasing glycogen deposition in the liver and skeletal muscles. EPPH inhibits stress-related signaling and elevates hippocampal neurotrophic factors to improve cognitive function. EPPH also reduces oxidative stress and inflammation in the skeletal muscles, liver, and brain. These findings suggest that EPPH is a potential therapeutic agent for treating exercise-induced fatigue. Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal model. The objectives of the study were to examine the hypothesis and the action mechanism of EPPH in relieving physical and cognitive fatigue. Fifty male Sprague–Dawley rats aged 8 weeks (body weight: 201 g) were classified into five groups, and rats in each group were given oral distilled water, EPPH (5 mg nitrogen/mL) at doses of 0.08, 0.16, or 0.31 mL/kg body weight (BW)/day, or glutathione (100 mg/kg BW/day) by a feeding needle for 5 weeks, which were named as the control, L-EPPH, M-EPPH, H-EPPH, or positive-control groups, respectively. Ten additional rats had no intense exercise with water administration and were designated as the no-exercise group. After 2 weeks, the rats were subjected to intense exercise and forced swimming trial for 30 min once per week for an additional 4 weeks. At 5 min after the intense exercise, lactate concentrations and lactate dehydrogenase (LDH) activity in the serum and the gastrocnemius muscle were higher in the control group, whereas M-EPPH and H-EPPH treatments suppressed the increase better than in the positive-control (p < 0.05). Intense exercise decreased glycogen content in the liver and gastrocnemius muscle, and M-EPPH and H-EPPH inhibited the decrement (p < 0.05). Moreover, lipid peroxide contents in the gastrocnemius muscle and liver were higher in the control group than in the M-EPPH, H-EPPH, positive-control, and no-exercise groups (p < 0.05). However, antioxidant enzyme activities such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were opposite to the lipid peroxide contents. Hypothalamic corticosterone and hippocampal mRNA expressions of tumor necrosis factor (TNF)-α and IL-1β were higher. However, hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression and protein contents were lower in the control group than in the positive-control group. M-EPPH, H-EPPH, and positive-control suppressed the changes via activating hippocampal cAMP response element-binding protein phosphorylation, and H-EPPH showed better activity than in the positive-control (p < 0.05). In conclusion, EPPH (0.16–0.31 mL/kg BW) intake reduced exercise-induced physical and cognitive fatigue in rats and could potentially be developed as a therapeutic agent for relieving fatigue in humans. [ABSTRACT FROM AUTHOR] more...

The gut microbiota has been demonstrated to play a critical role in maintaining cognitive function via the gut-brain axis, which may be related to the parasympathetic nervous system (PNS). However, the exact mechanism remains to be determined. We investigated that patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) could exhibit an altered gut microbiota through the suppression of the PNS, compared to the healthy individuals, using the combined gut microbiota data from previous human studies. The hypothesis was validated in rats to suppress the PNS by scopolamine injections. The human fecal bacterial FASTA/Q files were selected and combined from four different AD studies (n = 410). All rats had a high-fat diet and treatments for six weeks. The MD rats had memory impairment by scopolamine injection (2 mg/kg body weight; MD, Control) or no memory impairment by saline injection. The scopolamine-injected rats had a donepezil intake as the positive group. In the optimal model generated from the XGboost analysis, Blautia luti, Pseudomonas mucidoiens, Escherichia marmotae, and Gemmiger formicillis showed a positive correlation with MCI while Escherichia fergusonii, Mycobacterium neglectum, and Lawsonibacter asaccharolyticus were positively correlated with AD in the participants with enterotype Bacteroides (ET-B, n = 369). The predominant bacteria in the AD group were negatively associated in the networking analysis with the bacteria in the healthy group of ET-B participants. From the animal study, the relative abundance of Bacteroides and Bilophilia was lower, and that of Escherichia, Blautia, and Clostridium was higher in the scopolamine-induced memory deficit (MD) group than in the normal group. These results suggest that MCI was associated with the PNS suppression and could progress to AD by exacerbating the gut dysbiosis. MCI increased Clostridium and Blautia, and its progression to AD elevated Escherichia and Pseudomonas. Therefore, the modulation of the PNS might be linked to an altered gut microbiota and brain function, potentially through the gut-brain axis. [ABSTRACT FROM AUTHOR] more...

Bioactive compounds in some herbs can, directly and indirectly, protect against photoaging. We evaluated the effects of Gastrodia elata Blume (GE) and Poria cocos Wolf (PC) water extracts on ultraviolet (UV) B-induced skin lesions by acute UVB exposure in ICR mice and explored their mechanism of action. After removing the hair on the back of the mice, UVB (280–310 nm) was exposed to the back for 30 min to induce skin damage. Four UVB exposure groups were divided into the following according to the local application (1,3-butanediol extract) on the dorsal skin and oral intake (0.3 g water extract/kg body weight/day): 1,3-butanediol and cellulose(control; UV-Con), retinoic acid (positive-control; UV-Positive), PC extracts (UV-PC), and GE extracts (UV-GE). The fifth group had no UVB exposure with the same treatment as the UV-Con (Normal-control). The erythema, burns, erosion, and wounds of the UV-PC and UV-PC groups were alleviated, and the most significant improvements occurred in the UV-PC group. PC and GE reduced the thickness of the dorsal skin tissue, the penetration of mast cells, and malondialdehyde contents. The mRNA expression of TNF-α, IL-13, and IL-4, inflammatory factors, were also reduced significantly in the dorsal skin of the UV-PC and UV-GE groups. UV-PC, UV-GE, and UV-Positive showed improvements in UV-induced intestinal tissue inflammation. UV-Con deteriorated the intestinal morphology, and PC and GE alleviated it. The α-diversity of the fecal microbiota decreased in the UV-control, and UV-PC and UV-GE prevented the decrease. Fecal metagenome analysis revealed increased propionate biosynthesis in the UV-PC group but decreased lipopolysaccharide biosynthesis in the UV-PC and UV-GE groups compared to UV-Con. In conclusion, the local application and intake of PC and GE had significant therapeutic effects on acute UV-induced skin damage by reducing oxidative stress and proinflammatory cytokines, potentially promoting the gut-microbiota-gut-skin axis. [ABSTRACT FROM AUTHOR] more...

Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer's disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and λ-carrageenan would improve memory impairment in Alzheimer's disease-induced rats caused by an infusion of toxic amyloid-β(Aβ). Fucoidan and λ-carrageenan were dissected into low-MW by Luteolibacter algae and Pseudoalteromonas carrageenovora. Rats receiving an Aβ(25–35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW λ-carrageenan (AD-C-H), and 1% low-MW λ-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3→pAkt→pGSK-3β pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating. [ABSTRACT FROM AUTHOR] more...

A high salt intake may exacerbate menopausal symptoms and substituting for different types of traditionally made kanjang (TMK; soy sauce) may prevent it. This study examined whether substituting salt with lyophilized TMK containing low and high Bacillus and biogenic amines in a high-fat diet might modulate the menopausal symptoms and the energy, glucose, and lipid metabolism in ovariectomized (OVX) rats. They were categorized into salt (Control), TMK with high Bacillus and low biogenic amines (HBLB), TMK with high Bacillus and high biogenic amines (HBHB), TMK with low Bacillus and low biogenic amines (LBLB), and TMK with low Bacillus and high biogenic amines (LBHB). Sham-operated rats consumed the same diet as the Control. HBLB, HBHB, and LBHB prevented increased tail skin temperature compared to the Control. HBHB and HBLB partially inhibited the increased weight gain and abdominal fat mass by reducing the food efficiency without changing the serum 17β-estradiol concentrations. Serum glucose and insulin concentrations and the insulin resistance index by the homeostatic model assessment for insulin resistance showed a positive association for weight gain. HBLB and HBHB decreased the serum malondialdehyde and tumor-necrosis factor-α levels. Hepatic triglyceride storage was lower in all TMK groups than in the Control, while hepatic glycogen accumulation was higher in the HBLB, HBHB, and LBHB groups than in the Control and LBLB groups. Accordingly, the mRNA expression of peroxisome proliferator-activated receptors-γ(PPAR-γ) was higher in the HBLB and HBHB groups compared to the Control, and that of fatty acid synthase was opposite to PPAR-γ expression. However, HBLB and HBHB improved dyslipidemia and insulin resistance compared to the Control, but their improvement did not reach that of the Normal-control. The acetic acid concentrations in the portal vein were lower in the LBLB than in the Control, while the butyric acid contents were higher in the LBHB and HBLB groups than in the Control. HBHB, HBLB, and LBHB elevated Akkermansia and Lactobacillus, and HBLB and LBLB increased Bacteroides and Ruminococcus compared to the Control. Polycyclic aromatic hydrocarbon degradation, bile acid synthesis, and unsaturated fatty acid biosynthesis were significantly higher in the HBLB group than in the Control group. In conclusion, substituting salts to TMK with a high Bacillus content regardless of the bioamine contents partially improved the menopausal symptoms and metabolic disturbance in estrogen-deficient animals. [ABSTRACT FROM AUTHOR] more...

Bile acid metabolism, involved with the digestion and absorption of nutrients in the gut, is linked to the gut microbiota community, greatly impacting the host's metabolism. We examined the hypothesis that the modulation of bile acid metabolism by dietary fat contents, gallbladder removal (GBX; cholecystectomy), and bile acid sequestrant (BAS; cholestyramine) treatment could alter energy, glucose, and lipid metabolism through the changes in the gut microbiota. Mice were randomly assigned to the following six groups: (1) Sham GBX surgery (Sham) + low fat/high carbohydrate diet (LFD), (2) Sham + high fat diet (HFD), (3) Sham + HFD + BAS, (4) GBX + LFD, (5) GBX + HFD, and (6) GBX + HFD + BAS. BAS groups received 2% cholestyramine. After an 8-week intervention, energy, glucose, and lipid metabolism, and the gut microbiota community were measured. HFD groups exhibited higher body weight gain than LFD, and GBX increased the weight gain comped to Sham groups regardless of BAS in HFD (p < 0.05). Homeostatic model assessment for insulin resistance (HOMA-IR) was higher in HFD than LFD, and GBX increased it regardless of BAS. Serum lipid profiles were worsened in GBX + HFD compared to Sham + LFD, whereas BAS alleviated them, except for serum HDL cholesterol. Hepatic tumor-necrosis-factor-α (TNF-α) mRNA expression and lipid peroxide contents increased with GBX and BAS treatment compared to Sham and no BAS treatment (p < 0.05). Hepatic mRNA expression of sterol regulatory element-binding transcription factor 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma (PPAR-γ) exhibited the same trend as that of tumor necrosis factor-α (TNF-α). The α-diversity of gut bacteria decreased in GBX + HFD and increased in GBX + HFD + BAS. Akkermentia, Dehalobacterium, SMB53, and Megamonas were high in the Sham + LFD, and Veillonella and Streptococcus were rich in the Sham + HFD, while Oscillospira and Olsenella were high in Sham + HFD + BAS (p < 0.05). GBX + LFD increased Lactobacillus and Sutterella while GBX + HFD + BAS elevated Clostridium, Alistipes, Blautia, Eubacterium, and Coprobacillus (p < 0.05). In conclusion, the modulation of bile acid metabolism influences energy, glucose, and lipid metabolisms, and it might be linked to changes in the gut microbiota by bile acid metabolism modulation. [ABSTRACT FROM AUTHOR] more...

No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague–Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-α and IL-1β concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-α contents and mRNA TNF-α and IL-1β expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the α-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5–4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment. [ABSTRACT FROM AUTHOR] more...

Background: Insulin resistance is a common etiology of metabolic syndrome, but receiver operating characteristic (ROC) curve analysis shows a weak association in Koreans. Using a machine learning (ML) approach, we aimed to generate the best model for predicting insulin resistance in Korean adults aged > 40 of the Ansan/Ansung cohort using a machine learning (ML) approach. Methods: The demographic, anthropometric, biochemical, genetic, nutrient, and lifestyle variables of 8842 participants were included. The polygenetic risk scores (PRS) generated by a genome-wide association study were added to represent the genetic impact of insulin resistance. They were divided randomly into the training (n = 7037) and test (n = 1769) sets. Potentially important features were selected in the highest area under the curve (AUC) of the ROC curve from 99 features using seven different ML algorithms. The AUC target was ≥0.85 for the best prediction of insulin resistance with the lowest number of features. Results: The cutoff of insulin resistance defined with HOMA-IR was 2.31 using logistic regression before conducting ML. XGBoost and logistic regression algorithms generated the highest AUC (0.86) of the prediction models using 99 features, while the random forest algorithm generated a model with 0.82 AUC. These models showed high accuracy and k-fold values (>0.85). The prediction model containing 15 features had the highest AUC of the ROC curve in XGBoost and random forest algorithms. PRS was one of 15 features. The final prediction models for insulin resistance were generated with the same nine features in the XGBoost (AUC = 0.86), random forest (AUC = 0.84), and artificial neural network (AUC = 0.86) algorithms. The model included the fasting serum glucose, ALT, total bilirubin, HDL concentrations, waist circumference, body fat, pulse, season to enroll in the study, and gender. Conclusion: The liver function, regular pulse checking, and seasonal variation in addition to metabolic syndrome components should be considered to predict insulin resistance in Koreans aged over 40 years. [ABSTRACT FROM AUTHOR] more...

Short-term fermented soybeans (chungkookjang) with specific Bacillus (B.) spp. have anti-obesity, antidiabetic, and anti-stroke functions. We examined the hypothesis that the long-term consumption of B. amyloliquefaciens SCGB 1 fermented (CKJ1) and B. subtilis SCDB 291 (CKJ291) chungkookjang can alleviate clinical symptoms and hyperglycemia after ischemic stroke by promoting the gut microbiota–brain axis. We examined this hypothesis in Mongolian male gerbils with stroke symptoms induced by carotid artery occlusion. The artery-occluded gerbils were divided into five groups: no supplementation (Control, Normal-control), 4% cooked soybeans (CSB), CKJ1, or CKJ291 in a high-fat diet for 3 weeks. The carotid arteries of gerbils in the Control, CSB, CKJ1, and CKJ291 groups were occluded for 8 min and they then continued on their assigned diets for an additional 3 weeks. Normal-control gerbils had no artery occlusion. The diets in all groups contained an identical macronutrient composition using starch, casein, soybean oil, and dietary fiber. The CSB, CKJ1, and CKJ291 groups exhibited less neuronal cell death than the Control group, while the CKJ1 group produced the most significant reduction among all groups, as much as 85% of the Normal-control group. CKJ1 and CKJ291 increased the blood flow and removal of blood clots, as determined by Doppler, more than the Control. They also showed more improvement in neurological disorders from ischemic stroke. Their improvement showed a similar tendency as neuronal cell death. CKJ1 treatment improved memory impairment, measured with Y maze and passive avoidance tests, similar to the Normal-control. The gerbils in the Control group had post-stroke hyperglycemia due to decreased insulin sensitivity and β-cell function and mass; the CKJ291, CSB, and CKJ1 treatments protected against glucose disturbance after artery occlusion and were similar to the Normal-control. CKJ1 and CKJ291 also reduced serum tumor necrosis factor-α concentrations and hippocampal interleukin-1β expression levels, compared to the Control. CKJ1 and CKJ291 increased the contents of Lactobacillus, Bacillus, and Akkermansia in the cecum feces, similar to the Normal-control. Picrust2 analysis showed that CKJ1 and CKJ291 increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced the lipopolysaccharide biosynthesis and fatty acid metabolism compared to the Control. In conclusion, daily CKJ1 and CKJ291 intake prevented neuronal cell death and memory dysfunction from the artery occlusion by increasing blood flow and β-cell survival and reducing post-stroke-hyperglycemia through modulating the gut microbiome composition and metabolites to influence the host metabolism, especially inflammation and insulin resistance, protecting against neuronal cell death and brain dysfunction. CKJ1 had better effects than CKJ291. [ABSTRACT FROM AUTHOR] more...

Background: Skeletal muscle mass (SMM) and fat mass (FM) are essentially required for health and quality of life in older adults. Objective: To generate the best SMM and FM prediction models using machine learning models incorporating socioeconomic, lifestyle, and biochemical parameters and the urban hospital-based Ansan/Ansung cohort, and to determine relations between SMM and FM and metabolic syndrome and its components in this cohort. Methods: SMM and FM data measured using an Inbody 4.0 unit in 90% of Ansan/Ansung cohort participants were used to train seven machine learning algorithms. The ten most essential predictors from 1411 variables were selected by: (1) Manually filtering out 48 variables, (2) generating best models by random grid mode in a training set, and (3) comparing the accuracy of the models in a test set. The seven trained models' accuracy was evaluated using mean-square errors (MSE), mean absolute errors (MAE), and R² values in 10% of the test set. SMM and FM of the 31,025 participants in the Ansan/Ansung cohort were predicted using the best prediction models (XGBoost for SMM and artificial neural network for FM). Metabolic syndrome and its components were compared between four groups categorized by 50 percentiles of predicted SMM and FM values in the cohort. Results: The best prediction models for SMM and FM were constructed using XGBoost (R2 = 0.82) and artificial neural network (ANN; R2 = 0.89) algorithms, respectively; both models had a low MSE. Serum platelet concentrations and GFR were identified as new biomarkers of SMM, and serum platelet and bilirubin concentrations were found to predict FM. Predicted SMM and FM values were significantly and positively correlated with grip strength (r = 0.726) and BMI (r = 0.915, p < 0.05), respectively. Grip strengths in the high-SMM groups of both genders were significantly higher than in low-SMM groups (p < 0.05), and blood glucose and hemoglobin A1c in high-FM groups were higher than in low-FM groups for both genders (p < 0.05). Conclusion: The models generated by XGBoost and ANN algorithms exhibited good accuracy for estimating SMM and FM, respectively. The prediction models take into account the actual clinical use since they included a small number of required features, and the features can be obtained in outpatients. SMM and FM predicted using the two models well represented the risk of low SMM and high fat in a clinical setting. [ABSTRACT FROM AUTHOR] more...

Metabolic syndrome is associated with usual dietary patterns that may be involved in enterotypes. We aimed to understand the potential relationship of enterotypes and dietary patterns to influence metabolic syndrome in the Koreans. Using the Korea National Health and Nutrition Examination Survey (KNHANES)-VI in 2014, metabolic parameters were also analyzed among the dietary patterns classified by principal component analysis in Korean adults. The fecal microbiota data of 1199 Korean adults collected in 2014 were obtained from the Korea Centers for Disease Control and Prevention. Enterotypes were classified based on Dirichlet multinomial mixtures (DMM) by Mothur v.1.36. The functional abundance of fecal bacteria was analyzed using the PICRUSt2 pipeline. Korean adults were clustered into three dietary patterns including Korean-style balanced diets (KBD, 20.4%), rice-based diets (RBD, 17.2%), and Western-style diets (WSD, 62.4%) in KNHANES. The incidence of metabolic syndrome was lowered in the order of RBD, WSD, and KBD. The participants having a KBD had lower serum C-reactive protein and triglyceride concentrations than those with RBD and WSD (p < 0.05). Three types of fecal bacteria were classified as Ruminococcaceae type (ET-R, 28.7%), Prevotella type (ET-P, 52.2%), and Bacteroides type (ET-B, 42.1%; p < 0.05). ET-P had a higher abundance of Prevotella copri, while ET-R contained a higher abundance of Alistipes, Akkermansia muciniphila, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. ET-B had a higher abundance of the order Bilophila (p < 0.05). Metabolism of propanoate, starch, and sucrose in fecal microbiome was higher in ET-P and ET-R, whereas fatty acid metabolism was enhanced in ET-B. Fecal microbiota in ET-P and ET-B had higher lipopolysaccharide biosynthesis activity than that in ET-R. The metabolic results of KBD and RBD were consistent with ET-R and ET-P's gut microbiota metabolism, respectively. In conclusion, Korean enterotypes of ET-P, ET-B, and ET-R were associated with RBD, WSD, and KBD, respectively. This study suggests a potential link between dietary patterns, metabolic syndrome, and enterotypes among Korean adults. [ABSTRACT FROM AUTHOR] more...

Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be related to gut microbes. Schizonepeta Tenuifolia Briquet (STB) and Alpinia Oxyphylla Miquel (AOM) has traditionally been used for anti-inflammatory activity. We evaluated the effects of STB, AOM and STB+AOM extracts on 2,4-dinitro-1-chlorobenzene (DNCB)-induced AD skin lesions in Nc/Nga mice and action mechanism was explored. AD lesions were induced in the dorsal skin of Nc/Nga mice by topical application of 1% followed by 0.2% DNCB. After DNCB was applied, the mice had topical applications of either 30% water, 0.01% dexamethasone, 30% STB, 30% AOM, 15% STB + 15% AOM extracts in butylene glycol (BG). Each group was also fed corresponding high-fat diets with 1% dextrin (AD-Con and AD-Positive), 1% STB (AD-STB), 1% AOM (AD-AOM) and 0.5% STB + 0.5% (AD-MIX). Normal-control mice had no DNCB application. The study evaluated the skin AD severity, scratching behavior and weight changes of AD mice for 5 weeks. Compared with AD-Con, AD-STB, AD-AOM and AD-MIX alleviated the clinical AD symptoms (erythema, pruritus, edema, erosion and lichenification and scratching behaviors), normalized immune chemistry (serum IgE concentration, mast cells and eosinophil infiltration), improved skin hyperplasia and enhanced the gut microbiome. AD-STB, AD-AOM, AD-MIX and AD-positive treatments inhibited cutaneous mRNA expression of TNF-α, IL-4 and IL-13 and serum IgE concentrations. AD-MIX most effectively reduced clinical AD symptoms and proinflammatory cytokines. AD-Positive also reduced them but serum GOT and GPT concentrations were abnormally high. AD-STB and AD-MIX increased the alpha-diversity of fecal bacteria and reduced the serum acetate concentration, compared to the AD-Con. In conclusion, the mixture of STB and AOM is effective for treating AD symptoms locally and systemically without adverse effects and are potential interventions for atopic dermatitis. [ABSTRACT FROM AUTHOR] more...

Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control more...

Rice porridge containing Allium fistulosum (Welsh onion) root water extract (RAFR) has anti-inflammatory bioactive compounds. We examined whether the long-term administration of rice porridge with RAFR would prevent or delay the progression of osteoarthritis and menopausal symptoms in estrogen-deficient animals by ovariectomy. The rats consumed 40% fat energy diets containing 250 mg RAFR (rice: Allium fistulosum root = 13:1)/kg body weight (bw) (OVX-OA-RAFR-Low), 750 mg RAFR/kg bw (OVX-OA-RAFR-High) and 750 mg starch and protein/kg bw(OVX), respectively. After consuming the assigned diets for eight weeks, monoiodoacetate (OVX-OA) or saline (OVX) were injected into the knee joints of the rats for an additional three weeks. Sham rats were administered saline injections (normal-control). OVX-OA-RAFR improved oral glucose tolerance and also protected against decreases in bone mineral density and lean body mass in the legs and increases in fat mass in the abdomen, compared to the OVX and OVX-OA. OVX-OA-RAFR improved swelling and limping scores, normalized weight distribution between the osteoarthritic and normal limbs, and increased maximum running speeds compared to the OVX-OA. The OVX-OA deteriorated the articular cartilage by reducing the articular matrix and bone loss in the knee joint and it prevented knee joint deterioration when compared to the OVX. The improvement in osteoarthritis symptoms in OVX-OA-RAFR decreased the mRNA expression of matrix metallo-proteinase-1 and matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1β and interleukin-6 in the articular cartilage compared to OVX-OA rats. In conclusions, RAFR is effective in treating osteoarthritis symptoms and it may be used for a therapeutic agent in osteoarthritis-induced menopausal women. [ABSTRACT FROM AUTHOR] more...