The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.

Postoperative insulin resistance (IR) is a metabolic disorder characterized by decreased insulin sensitivity and elevated blood glucose levels following major surgery. Our previous clinical study identified a notable correlation between postoperative IR and gut microbiota, particularly butyrate-producing bacteria, yet the mechanisms remain unclear. In this study, we established gastric resection SD rat models to evaluate the impact of Clostridium butyricum NCU-27 (butyrate-producing bacteria) on postoperative IR. The results demonstrated significant reductions in fasting blood glucose (FBG), fasting insulin (FIns) levels, and HOMA-IR (6.64 ± 0.76 vs. 11.47 ± 1.32; 4.27 ± 0.59 vs. 7.40 ± 0.54) in the postoperative period compared to the control group (P < 0.05). Additionally, glucose tolerance and hepatic glycogen content were markedly improved (P < 0.001). Further exploration of butyrate demonstrated effects similar to C. butyricum NCU-27, potentially mediated through the gut-liver axis by inhibiting mTORC1 expression in liver cells, activating the IRS1/AKT pathway, enhancing glucose uptake and glycogen synthesis, suppressing gluconeogenesis, increasing insulin sensitivity, and improving IR. Finally, the use of mTORC1 agonists and inhibitors further confirmed the critical role of the mTORC1 pathway in mediating the beneficial effects of C. butyricum NCU-27 and butyrate on postoperative IR. In conclusion, this study elucidated that C. butyricum NCU-27 improves postoperative IR by regulating butyrate metabolism and inhibiting the mTORC1 pathway, offering new insights for preventing and treating post-gastrectomy IR.

Identifying dietary patterns in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is critical, since nutrition is a modifiable risk factor that contributes to the etiology and progression of the disease. This study evaluated the association between dietary patterns and lipid and glycemic profiles, liver biomarkers, and degrees of steatosis and fibrosis in patients with MASLD. In this cross-sectional study, 70 patients who completed the entire dietary assessment were included in the analyses. Dietary intake was assessed through 24-hour dietary recalls, and 4 dietary patterns were identified by exploratory factor analysis and principal component analysis. Mean scores were analyzed by sex, age group, and nutritional status, and associations with main outcomes were tested by binomial logistic regression, with significance set at P > .05. There was greater adherence to the prudent pattern among men (95% CI 2.1-2.84), which consisted of fresh fruits and fruit juices, whole grains and breads, eggs and egg-based preparations, and coffee and tea, and a lower chance of advanced steatosis in individuals with greater adherence to the traditional Brazilian pattern (OR 0.46, 95% CI 0.20-0.97). This pattern, based on minimally processed foods rich in fiber, bioactive compounds, and antioxidants, was shown to be protective against advanced steatosis.

Gastrointestinal (GI) cancers remain a leading cause of cancer-related mortality worldwide, with metabolic reprogramming recognized as a central driver of tumor progression and therapeutic resistance. Among the key regulatory layers, N6-methyladenosine (m6A) RNA modification-mediated by methyltransferases (writers such as METTL3/14), RNA-binding proteins (readers like YTHDFs and IGF2BPs), and demethylases (erasers including FTO and ALKBH5), plays a pivotal role in controlling gene expression and metabolic flux in the tumor context. Concurrently, the gut microbiota profoundly influences GI tumorigenesis and immune evasion by modulating metabolite availability and remodeling the tumor microenvironment. Recent evidence has uncovered a bidirectional crosstalk between microbial metabolites and m6A methylation: microbiota-derived signals dynamically regulate m6A deposition on metabolic and immune transcripts, while m6A modifications, in turn, regulate the stability and translation of key mRNAs such as PD-L1 and FOXP3. This reciprocal interaction forms self-reinforcing epigenetic circuits that drive tumor plasticity, immune escape, and metabolic adaptation. In this review, we dissect the molecular underpinnings of the microbiota-m6A-metabolism axis in GI cancers and explore its potential to inform novel strategies in immunotherapy, metabolic intervention, and microbiome-guided precision oncology.

The embryo implantation quality during early pregnancy is the predominant factor for embryo survival and litter performance in sows. Gut microbiota is demonstrated to show a correlation to pregnancy outcomes by participating in regulating maternal metabolism. However, the specific functional microbiota and its mechanical effects on regulating embryo implantation and survival remain unclear. The objective of this study was to clarify whether embryo implantation and litter performance were affected by maternal intestinal microbiota, and to identify specific microbial communities and its mechanism in regulating embryo implantation.

In this study, we first conducted 16S rRNA sequencing and metabolomic analysis revealing the intestinal microbiota and metabolism of 42 sows with different litter size to select the potential functional microbiota that may contribute to embryo survival. Then, we explored the effects of that microbiota on embryo implantation and litter performance through microbiota transplantation in mice and sows. We found that maternal intestinal L. vaginalis exhibits enrichment in sows with higher litter size, which could facilitate embryo implantation and survival and ultimately increases litter size in mice. We further employed transcriptomic analysis to determine the characteristics of uterus, which found an enhanced uterine receptivity after L. vaginalis gavage. The plasma untargeted metabolomic analysis after L. vaginalis gavage in mice and targeted metabolomics analysis of in vitro cultured medium of L. vaginalis were used to evaluate the metabolic regulation of L. vaginalis and to reveal the underlying functional metabolites. Next, an increasing adhesion rate of endometrial-embryonic cells and an obvious increasing formation of pinopodes in cell surface of porcine endometrial epithelial cells were observed after treatments of L. vaginalis metabolites, especially galangin and daidzein. Also, the gene expression levels related to uterine receptivity were increased after treatments of L. vaginalis metabolites in porcine endometrial epithelial cells. Finally, we found that L. vaginalis or its metabolites supplementation during early gestation significantly increased the litter performance in sows.

Overall, intestinal microbial-host interactions can occur during early pregnancy and may be contribute to maternal metabolic changes and influence pregnancy outcomes in mammals. Our study provides insights of maternal intestinal L. vaginalis to enhance uterine receptivity and to benefit embryo/fetal survival through a gut-uterus axis, contributing to advanced concept and novel strategy to manipulate gut microbiota during early pregnancy, and in turn to improve embryo implantation and reduce embryo loss in sows. Video Abstract.

Oral microbiota and serum metabolites play crucial roles in diabetes, but their relationship with post-transplant diabetes mellitus (PTDM), a common complication post-kidney transplantation, is not well characterized. This study investigated the relationship of oral microbiota and serum metabolites with PTDM using integrative analysis of 16S rDNA sequencing and serum metabolomics. We recruited 61 kidney transplant recipients, including 30 in the PTDM group and 31 in normal glucose tolerance controls. Oral samples and serum samples were collected from all the kidney transplant patients to perform 16S rDNA sequencing and serum metabolomics analysis. We annotated 689 oral microbial species, including 134 species unique to the PTDM group and 157 species unique to the control group. PTDM group showed upregulation of 36 metabolites and downregulation of 19 metabolites. Based on the random forest machine learning algorithm, genera such as UCG-005 (AUC = 0.9355), Succinivibrio (AUC = 0.8108); Akkermansia (AUC = 0.7742), Anaerovibrio (AUC = 0.2667), and Schwartzia (AUC = 0.2667), and serum metabolites such as LPI 18:0 (AUC: 0.8086), methylglyoxal (AUC: 0.7946), Vulgarin (AUC: 0.7828), 2-mercaptobenzothiazole (AUC: 0.7591), and PI(18:0/20:3(5Z,8Z,11Z)) (AUC: 0.7419) showed high diagnostic potential and may serve as clinical biomarkers. Furthermore, clinical indicators in PTDM patients, such as creatinine, cystatin C, and urea, showed a significant association with the differential oral microbiota and serum metabolites. Dysbiosis in the oral microbiota of the PTDM patients was associated with changes in the serum metabolites and alterations in their functions. These findings provide new insights toward identifying mechanisms by which oral microbiota and serum metabolites contribute to the development of PTDM.IMPORTANCEThis study reveals an imbalance in oral microbiota in patients with post-transplant diabetes and uncovers the potential relationship between oral microbiota and serum metabolites. These findings provide new insights into the role of oral microbiota and serum metabolites in the treatment of post-transplant diabetes, offering relevant biomarkers for clinicians and future research.

The gut microbiome has been identified as a significant factor in host metabolism, playing a key role in the etiology of obesity, type 2 diabetes and cardiometabolic risk. Butyrate, produced by the gut microbiome from indigestible carbohydrates, has been shown to have beneficial effects on body weight control, inflammation, and insulin resistance, primarily evidenced by animal studies and in vitro experiments. However, translating these benefits to humans remains challenging due to variability in mode of butyrate administration or production upon fermentation of dietary fibers, as well as in butyrate absorption, and its metabolism. For instance, oral butyrate supplementation can directly increase circulating butyrate levels, thereby targeting peripheral tissues. In contrast, butyrate produced by the gut microbiome may also influence metabolism through local signaling mechanisms affecting peripheral tissues. Additionally, there may be large heterogeneity in the response of the individuals to butyrate interventions. Future research should aim to better understand butyrate kinetics and dynamics and its mechanisms in regulating intestinal and metabolic health. In human studies, longer-term, placebo-controlled trials are needed to establish the efficacy of either targeting butyrate production or supplementation in individuals with obesity and/or metabolic disturbances. Personalized dietary interventions based on individual microbiota composition and/or function and metabolic profiles may optimize butyrate production and its metabolic benefits. This could pave the way for effective butyrate-based interventions to improve metabolic health and prevent obesity-related complications.

Although preclinical data support the hypothesis that butyric acid supplementation improves kidney health, the clinical significance of dietary butyric acid intake in patients with chronic kidney disease (CKD) remains unconfirmed in large-sample studies. This study aimed to investigate the association between dietary butyric acid intake and all-cause mortality in the United States population, stratified by kidney function.

We examined the relationship between dietary butyric acid intake, assessed through a 24-h dietary recall, and all-cause mortality among 23,008 consecutive adult participants from the National Health and Nutrition Examination Surveys (NHANES, 2005-2018), categorized by impaired versus normal kidney function (estimated glomerular filtration rate <60 vs ≥ 60 mL/min/1.72 m2), using multivariable Cox models. We also employed a restricted cubic spline based on Cox regression models to elucidate the nonlinear relationship between dietary butyric acid intake and mortality in patients.

In participants with impaired kidney function, high dietary butyric acid intake was associated with lower mortality, while lower intake levels (reference) showed no such association: adjusted HRs (aHRs) were 0.67 (95 % CI: 0.45, 1.00), 0.65 (95 % CI: 0.45, 0.94), and 0.58 (95 % CI: 0.38, 0.89) for intake levels of the square root of butyric acid 0.25-0.45, 0.45-0.75, and >0.75 g/day, respectively. However, in participants with normal kidney function, no association between butyric acid levels and mortality was observed. Additionally, we identified an L-shaped association between the levels of the square root of dietary butyric acid intake and all-cause mortality in the CKD population, reaching a plateau at 0.52 g/day (butyric acid intake of approximately 0.27 g/day).

This study revealed a nonlinear association between high dietary butyric acid intake and reduced all-cause mortality in patients with chronic kidney disease. A plateau occurs after 0.27 g/day, and for individuals with CKD whose butyric acid intake is below approximately 0.27 g/day, increasing a butyrate-rich diet or supplementing with butyric acid preparations may help prevent progression to renal failure and associated adverse outcomes in CKD patients, thereby reducing mortality. Therefore, it can be considered a new therapeutic strategy for the treatment of chronic kidney disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unclear causes and limited treatment options. Sodium butyrate (NaB), a byproduct of dietary fiber in the intestine, has demonstrated efficacy in treating inflammation. However, the precise anti-inflammatory mechanisms of NaB in colon inflammation remain largely unexplored. This study aims to investigate the effects of NaB on dextran sulfate sodium (DSS)-induced colitis in rats. The findings indicate that oral administration of NaB effectively prevent colitis and reduce levels of serum or colon inflammatory factors. Additionally, NaB demonstrated in vitro inhibition of RAW264.7 inflammation cytokines induced by LPS, along with suppression of the ERK and NF-κB signaling pathway activation. Moreover, NaB mitigated LPS and Nigericin-induced RAW264.7 pyroptosis by reducing indicators of mitochondrial damage, including increased mitochondrial membrane potential (JC-1) levels and decreased Mito-ROS production. NaB increases ZO-1 and Occludin expression in CaCo2 cells by inhibiting RAW264.7 pyroptosis. These results suggest that NaB could be utilized as a therapeutic agent or dietary supplement to alleviate colitis.

Cholera, a diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, remains a global health threat in developing countries due to its high transmissibility and increased antibiotic resistance. There is a pressing need for alternative strategies, with an emphasis on anti-virulent approaches to alter the outcome of bacterial infections, given the increase in antimicrobial-resistant strains. V. cholerae causes cholera by secreting virulence factors in the intestinal epithelial cells. These virulence factors facilitate bacterial colonization and cholera toxin production during infection. Here, we demonstrate that sodium butyrate (SB), a small molecule, had no effect on bacterial viability but was effective in suppressing the virulence attributes of V. cholerae. The production of cholera toxin (CT) was significantly reduced in a standard V. cholerae El Tor strain and two clinical isolates when grown in the presence of SB. Analysis of mRNA and protein levels further revealed that SB reduced the expression of the ToxT-dependent virulence genes like tcpA and ctxAB. DNA-protein interaction assays, conducted at cellular (ChIP) and in vitro conditions (EMSA), indicated that SB weakens the binding between ToxT and its downstream promoter DNA, likely by blocking DNA binding. Furthermore, the anti-virulence efficacy of SB was confirmed in animal models. These findings suggest that SB could be developed as an anti-virulence agent against V. cholerae, serving as a potential alternative to conventional antibiotics or as an adjunctive therapy to combat cholera.

The world has been facing an upsurge in cholera cases since 2021, a similar trend continuing into 2022, with over 29 countries reporting cholera outbreaks (World Health Organization, 16 December 2022, Disease Outbreak News, Cholera-global situation). Treatment of cholera involves oral rehydration therapy coupled with antibiotics to reduce the duration of the illness. However, in recent years, indiscriminate use of antibiotics has contributed to the emergence of antibiotic-resistant strains. In this study, we have addressed the problem of antibiotic resistance by targeting virulence factors. Screening various compounds using in silico methods led to the identification of a small molecule, SB, that inhibits the virulence cascade in V. cholerae. We demonstrated that (i) SB intervened in ToxT protein-DNA binding and subsequently affected the expression of ToxT-regulated virulence genes (ctxAB and tcpA) and (ii) SB is a potential therapeutic candidate for the development of a novel antimicrobial agent.

The coating of microbiota by secretory immunoglobulins (sIgs) determines which bacteria colonize the gut and influences bacterial metabolism. Previous work has identified sIgA and sIgT as mediators of gut homeostasis. However, sIgM coats a large proportion of the gut microbiota in humans and teleost fish, thus suggesting a conserved role of sIgM in microbiota homeostasis. Here, to investigate this hypothesis, we used the teleost rainbow trout as a model system. Depletion of IgM from trout resulted in severe microbiota-dependent gut tissue damage, body weight loss, bacterial translocation and gut dysbiosis. IgM depletion led also to alterations in microbiota-derived metabolites, including short-chain fatty acids and essential amino acids. Supporting a protective role for sIgM in the gut, high mortality of IgM-depleted fish occurred in an experimental colitis model as a result of severe systemic bacteraemia and septic shock. Our findings uncover sIgM as a previously unrecognized regulator of microbiota homeostasis and metabolism.

Intestinal ischemia-reperfusion injury (II/RI) is a critical acute condition characterized by complex pathological mechanisms, including various modes of cell death. Among these, pyroptosis has garnered significant attention in recent years. This review explores the characteristics, molecular mechanisms, and implications of pyroptosis in II/RI, with a focus on therapeutic strategies targeting the pyroptosis pathway. Key processes such as NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation, caspase-1 activation, and gasdermin D (GSDMD)-mediated membrane pore formation are identified as central to pyroptosis. Compounds like MCC950, CY-09, metformin, and curcumin have shown promise in attenuating II/RI in preclinical studies by modulating these pathways. However, challenges remain in understanding non-canonical pyroptosis pathways, unraveling the exact mechanisms of GSDMD-induced pore formation, and translating these findings into clinical applications. Addressing these gaps will be crucial for developing innovative and effective treatments for II/RI.

This study aimed to investigate the efficacy of polysaccharides from Artemisia sphaerocephala Krasch (ASK) seed in alleviating high fat diet (HFD) caused obesity. Here, three polysaccharide fractions (ASKP1, ASKP2 and ASKP3) were purified from ASK seed. Chemical characteristic analysis revealed that ASKP1 is a neutral heteropolysaccharide with the average molecular weight of 9.08 × 105 Da, while ASKP2 and ASKP3 are acidic heteropolysaccharides with the molecular weight of 9.39 × 105 and 8.41 × 105 Da, respectively. Animal experiment found that three ASKP fractions obviously relieved obesity and related metabolic disorders induced by HFD, while ASKP1 was more effective in reducing the blood glucose and serum LDL levels. 16S rDNA sequencing showed that ASKP fractions improved the gut microbiota imbalance of obese mice, and ASKP1 promoted the proliferation of beneficial bacterium Akkermansia more effectively than ASKP2 and ASKP3. Furthermore, ASKP fractions facilitated thermogenesis of brown adipose tissue (BAT) of obese mice, as evidenced by increased expression of thermogenic marker genes UCP1 in BAT, and the thermogenesis effect of ASKP1 was the most obvious. Taken together, our results show that ASKP1 is a novel prebiotic that may be used to treat obesity and its related abnormal metabolism.

The objective of this research was to explore the changes of morphological parameters, short chain fatty acid contents and butyric acid transporter expression levels in the large intestine with growth and development of sucking lambs.

A total of 48 newborn male Hu sheep lambs (body weight = 2.94±0.22 kg) were selected in this experiment. At 0, 7, 14, 28 and 42 days of ages, 6 lambs were slaughtered to collect cecal and colonic samples to analyze morphological parameters, short chain fatty acid contents and butyric acid transporter mRNA expression.

The organ index of the cecum in d 0, 28 and 42 groups was higher (p<0.05) than that in d 7 and 14 groups. Compared with other age groups, the organ index of the colon was significantly increased (p<0.05) in d 42 group. After 7 days of age, the contents of acetic, propionic and butyric acids in the cecum and colon were significantly increased (p<0.05) as age increased. A similar trend of mRNA expressions of butyric acid transporters, including monocarboxylate transporter, sodium-coupled monocarboxylate transporter, sodium-hydrogen exchanger, down regulated in adenoma, putative anion transporter-1 and anion exchanger-2, was found. In the cecum, the Escherichia coli count in d 14 group was higher (p<0.05) than that in other age groups, whereas an opposite tendency was found in Lactobacillus count between d 14 and other groups. Additionally, in the cecum and colon, the relative expression of claudin-1 in d 14 group was lower (p<0.05) than in d 42 group.

Overall, the current results indicate that the expression levels of butyric acid transporters in the cecum and colon of lambs are significantly influenced by days of age.

Flaxseed (Linum usitatissimum L.) and chia seed (Salvia hispanica L.) have become increasingly popular in the design of various functional food products. However, information on their functional properties is scarce. The aim of this study is to comparatively evaluate the effects of the dietary fibers (DFs) of flaxseed and chia seed on colonic microbiota composition and metabolic outputs. The neutral and acidic monosaccharide compositions of DFs of flaxseed and chia seed were determined using gas chromatography/mass spectrometry (GC/MS) and spectrophotometer, respectively. Next, in vitro fecal fermentation assays were applied, and samples were collected at different time points for short-chain fatty acids (SCFA) measurements using GC, and fecal microbiota changes before and after fermentation were evaluated through 16S rRNA sequencing. The results revealed that DFs of flaxseed were dominated by xylose and uronic acid moieties, while that of chia seed was dominated by glucose units, indicating that their DFs are structurally different. Higher SCFA generations were observed in the case of flaxseed, suggesting that flaxseed DFs are more readily fermentable by gut microbiota. Flaxseed and chia seed DFs differentially impacted the microbiota compositions at the OTU level; for example, significant increases in the relative abundances of Acidaminococcaceae and Bacteroides stercoris related OTUs, which are known to be propionate producers, were observed in the case of flaxseed, but not chia seed. Interestingly, flaxseed, but not chia seed, DFs suppressed the growth of some pathogenic bacteria. Overall, this study suggests that the functionality of flaxseed and chia seed DFs in relation to colonic microbiota may differ, with flaxseed being more readily fermented and potentially promoting beneficial microbes to a greater extent. Thus, flaxseed could hold promise for developing functional food recipes aimed at supporting colonic health.

Prenatal alcohol exposure (PAE) can severely impact fetal development, including alterations to the developing immune system. Immune perturbations, in tandem with gut dysbiosis, have been linked to brain and behavioral dysfunction, but this relationship is poorly understood in the context of PAE. This study takes an ontogenetic approach to evaluate PAE-induced alterations to brain and serum cytokine levels and both the composition and metabolic output of the gut microbiota. Using a well-established rat model of PAE, cytokine levels in the serum, prefrontal cortex, amygdala, and hypothalamus as well as gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed at three postnatal (P) timepoints: P8 (infancy), P22 (weaning), and P38 (adolescence). Male PAE rats had increased cytokine levels in the amygdala and hypothalamus, but not prefrontal cortex, at P8. This altered neuroimmune function was not seen in the PAE females. The effect of PAE on central cytokine levels was reduced at P22/38, the same age at which PAE-induced alterations in serum cytokine levels emerge in both sexes. PAE reduced bacterial diversity in both sexes at P8, but only in females at P38, where a PAE-induced unique community composition emerged. Both sexes had alterations to specific bacterial taxa (e.g., Firmicutes), some of which are important in producing the SCFA butyric acid, which was decreased in PAE animals at P22. These results demonstrate that PAE leads to sex- and age-specific alterations in immune function, gut microbiota and SCFA production, highlighting the need to consider both age and sex in future work.

Although various prebiotics, probiotics, and postbiotics are available, their safety and efficacy in combination are unknown.

We investigated the safety and functionality of a newly developed supplement, previously unreported in pet animals, containing 26 types of biotic material bacteria (2 prebiotics, 1 probiotic, and 23 postbiotics) in cats and dogs. The biotic materials included were selected based on current evidence from cats and dogs.

A new supplement developed using species tested in cats and dogs was administered. One-way analysis was used for data obtained from 3 cats (7 days of treatment and 7 days of nontreatment), and a parallel, controlled study was performed in 20 dogs (n = 10 each in control and test groups, for 27 days).

In cats, no abnormal values were observed in complete blood count or blood chemistry tests, whereas significant decreases in blood glucose and total cholesterol were confirmed (p < 0.05 each). In the feline lymphocyte subset test, significant increases were observed in T and B cells (p < 0.05). A significant difference in fecal pH was observed in the test group (p < 0.01). In addition, 60% (9/15) of the test group had an increase in total organic acids. In dogs, only indole showed a consistent decrease among putrefactive products (p = 0.055). Regarding analyses of intestinal flora from feces using a gene sequencer at the genus level, no changes were observed in cats. Conversely, Lachnospira and Anaeroplasma genera tended to be decreased in the control group but increased by 23.1% and 45%, respectively, in the test group. In addition, Escherichia-Shigella and Tyzzerella genera showed slight increases or changes in the control group but significant decreases in the test group. Regarding the Firmicutes/Bacteroidetes ratio, an increase in the control group and a decrease in the test group were observed in all cats, whereas no differences were observed in dogs.

The supplement is safe for both cats and dogs. Results of comprehensive analyses suggested that the supplement improved the intestinal environment by regulating the gastrointestinal microbiota.

Gut microbiota are important for uric acid (UA) metabolism within hyperuricemia (HUA); however, the underlying mechanisms of how the gut microbiota regulate intestinal UA metabolism remain unclear. This study aimed to explore the function of the intestine in HUA and to further reveal the possible mechanism.

We conducted gut microbiota depletion to validate the role of gut microbiota in UA metabolism. A mouse model of HUA was established, and the gut microbiota and microbiome-derived metabolites were analyzed via 16S RNA gene sequencing and metabolomics analysis. The mechanism of the gut microbiota in HUA was elucidated by in vivo and in vitro experiments.

Antibiotic treatment elevated serum UA, disturbed purine metabolism, and decreased the relative abundance of Lactobacillus. HUA mice had a lower relative abundance of Lactobacillus johnsonii (L. johnsonii) and decreased gut butyrate concentration. Supplementation of L. johnsonii significantly reduces serum UA in hyperuricemia mice by preventing UA synthesis and promoting the excretion of gut purine metabolites. In addition, L. johnsonii enhanced intestinal UA excretion by heightening the urate transporter ABCG2 (adenosine triphosphate-binding cassette transporter, subfamily G, member 2) expression, and increasing the levels of butyrate, which upregulated ABCG2 expression via the Wnt5a/b/β-catenin signaling pathway.

Our results suggest that gut microbiota and microbiota-derived metabolites directly regulate gut UA metabolism, highlighting potential applications in the treatment of diet-induced HUA by targeting gut microbiota and its metabolites.

During cold stress, gut microbes play crucial roles in orchestrating energy metabolism to enhance environmental adaptation. In sheep, hindgut microbes ferment carbohydrates to generate short-chain fatty acids (SCFAs) as an energy source. However, the mechanisms by which hindgut microbes and their metabolites interact with the host to facilitate adaptation to cold environments remain ambiguous. Herein, we simulated a winter environment (- 20 °C) and provided a rationed diet to compare the cold adaptation mechanisms between Hulunbuir and Hu sheep.

Our findings show that cold exposure enhances SCFA metabolism in the sheep cecum. In Hu sheep, acetate, butyrate, and total SCFA concentrations increased, whereas in Hulunbuir sheep, propionate and butyrate concentrations increased, with a notable increase in total SCFAs. Notably, butyrate concentration was higher in Hulunbuir sheep than in Hu sheep under cold stress. Following cold exposure, the proinflammatory cytokine IL-1β levels increased in both breeds. In addition, Hu sheep showed increased IL-10, whereas Hulunbuir sheep exhibited elevated secretory IgA levels. The cecal microbiota responded differently, Hu sheep showed no notable changes in alpha and beta diversity, whereas Hulunbuir sheep exhibited considerable alterations. In Hu sheep, the abundance of fungi, specifically Blastocystis sp. subtype 4, decreased, and that of several Lachnospiraceae species (Roseburia hominis, Faecalicatena contorta, and Ruminococcus gnavus) involved in SCFA metabolism increased. Pathways related to carbohydrate metabolism, such as starch and sucrose metabolism, galactose metabolism, and pentose and glucuronate interconversions, were upregulated. In Hulunbuir sheep, the abundance of Treponema bryantii, Roseburia sp. 499, and Prevotella copri increased, with upregulation in pathways related to amino acid metabolism and energy metabolism. Cold exposure increased node connectivity within the symbiotic networks of both breeds, with increased network vulnerability in Hu sheep. Following cold exposure, the microbial community of Hulunbuir sheep showed a decrease in the influence of stochastic processes on community assembly, with a corresponding increase in the role of environmental selection. Conversely, no such shift was evident in Hu sheep. Further transcriptomic analysis revealed distinct regulatory mechanisms between breeds. In Hu sheep, protein synthesis, energy metabolism, and thermogenesis pathways were substantially upregulated. By contrast, Hulunbuir sheep showed considerable upregulation of immune pathways and energy conservation through reduced ribosome synthesis. Correlation analysis indicated that butyrate holds a central position in both networks, with Hulunbuir sheep exhibiting a more complex and tightly regulated network involving SCFAs, microbiota, microbial functions, and transcriptomes. Partial least squares path modeling revealed that cold exposure substantially altered the cecal microbiota and transcriptomes of Hulunbuir sheep, affecting SCFAs and cytokines.

The findings of this study suggest that under cold exposure, Hu sheep enhance acetate fermentation and rely on tissue thermogenesis for adaptation. By contrast, Hulunbuir sheep exhibit changes in microbial diversity and function, leading to increased propionate and butyrate metabolism. This may promote physiological energy conservation and innate immune defense, balancing heat loss and enhancing cold adaptation.

Various types of non-digestible oligosaccharides (NDOs) have attracted tremendous interest due to their healthy functions in regulating intestinal microbiota. Whereas the specificity of different NDOs towards certain intestinal bacterial species remains unclear. In this study, konjac manna-oligosaccharides (KMOS) were selected from eight NDOs through in vitro faecal batch fermentation. KMOS accelerated increase of recognised probiotics (Bifidobacterium spp. and Akkermansia spp.) and achieved the highest productions of lactic acid and total short-chain fatty acids (42.0 mM). β-Mannosidase and β-glucosidase played important role in the utilisation of KMOS, and mannobiose and glucosyl-mannobiose were preferentially consumed by faecal microbiota. In pure culture, the utilisation of KMOS was tested with nine Bifidobacterium strains. Amongst, KMOS increased the cell density of B. animalis BB-12 by 3.5 folds and improved its adhesion ability to Caco-2 cell by 3.1 folds, suggesting that KMOS and B. animalis BB-12 may be developed as a potential synbiotic combination.

This study investigated the longitudinal effects of acute (7-day) and prolonged (3-month) high-altitude exposure on gut microbiota in healthy adult males, addressing the limited data available in human populations. A cohort of 406 healthy adult males was followed, and fecal samples were collected at three time points: baseline at 800 m (406 samples), 7 days after ascending to 4,500 m (406 samples), and 2 weeks post-return to 800 m following 3 months at high altitude (186 samples). High-throughput 16S ribosomal DNA sequencing was employed to analyze microbiota composition and diversity. Results revealed significant changes in alpha- and beta-diversity, with acute high-altitude exposure inducing more pronounced effects compared to prolonged exposure. Specifically, acute exposure increased opportunistic pathogens (Ruminococcus and Oscillibacter) but decreased beneficial short-chain fatty acid producers (Faecalibacterium and Bifidobacterium). Notably, these changes in microbiota persisted even after returning to low altitude, indicating long-term remodeling. Functional analyses revealed substantial changes in metabolic pathways, suggesting microbiota-driven adaptations to energy utilization under high-altitude hypoxic conditions. In summary, acute high-altitude exposure caused dramatic changes in gut microbiota, while prolonged exposure led to structural and functional reshaping. These findings enhance our understanding of how high-altitude environments reshape gut microbiota.

This study is the first to investigate the impact of high-altitude exposure on gut microbiota adaptation in a large-scale longitudinal cohort. It seeks to enhance understanding of how high-altitude environments reshape gut microbiota. Acute exposure to high altitude significantly affected both α-diversity and β-diversity of gut microbiota, with acute exposure causing more pronounced changes than prolonged adaptation, indicating temporary disruptions in microbial communities. Notable shifts in microbial abundance were observed, including increased levels of genera linked to hypoxic stress (e.g., Gemmiger, Ruminococcus, and Parabacteroides) and decreased levels of beneficial bacteria (e.g., Faecalibacterium, Roseburia, and Bifidobacterium), suggesting possible adverse health effects. Functional analysis indicated changes in metabolism-related pathways post-exposure, supporting the idea that high-altitude adaptations involve metabolic adjustments for energy management. These findings enhance understanding of high-altitude physiology, illustrating the role of gut microbiota in hypoxic health.

Breakthroughs in metabolomics technology have revealed the direct regulatory role of metabolites in physiology and disease. Recent data have highlighted the bioactive metabolites involved in the etiology and prevention and treatment of metabolic diseases such as obesity, nonalcoholic fatty liver disease, type 2 diabetes mellitus, and atherosclerosis. Numerous studies reveal that endogenous metabolites biosynthesized by host organisms or gut microflora regulate metabolic responses and disorders. Lipids, amino acids, and bile acids, as endogenous metabolic modulators, regulate energy metabolism, insulin sensitivity, and immune response through multiple pathways, such as insulin signaling cascade, chemical modifications, and metabolite-macromolecule interactions. Furthermore, the gut microbial metabolites short-chain fatty acids, as signaling regulators have a variety of beneficial impacts in regulating energy metabolic homeostasis. In this review, we will summarize information about the roles of bioactive metabolites in the pathogenesis of many metabolic diseases. Furthermore, we discuss the potential value of metabolites in the promising preventive and therapeutic perspectives of human metabolic diseases.

In recent years, advancements in metagenomics, metabolomics, and single-cell sequencing have enhanced our understanding of the intricate relationships between gut microbiota and their hosts. Gut microbiota colonize humans from birth, with their initial composition significantly influenced by the mode of delivery and feeding method. During the transition from infancy to early childhood, exposure to a diverse diet and the maturation of the immune system lead to the gradual stabilization of gut microbiota's composition and distribution. Numerous studies have demonstrated that gut microbiota can influence a wide range of physiological functions and pathological processes by interacting with various tissues and organs through the gut-organ axis. Different intestinal segments exhibit unique physical and chemical conditions, which leads to the formation of vertical gradients along the intestinal tract: aerobes and facultative aerobes mainly live in the small intestine and anaerobic bacteria mainly live in the large intestine, and horizontal gradients: mucosa-associated microbiota and lumen-associated microbiota. In this review, we systematically summarize the distribution characteristics of gut microbiota across six intestinal segments: duodenum, jejunum, ileum, cecum, colon, and rectum. We also draw a conclusion that gut microbiota distributed in different intestinal segments affect the progression of different diseases. We hope to elucidate the role of microbiota at specific anatomic sites within the gut in precisely regulating the processes of particular diseases, thereby providing a solid foundation for developing novel diagnostic and therapeutic strategies for related diseases.

This study investigated whether the supplementation of prebiotic inulin to gestating sows programmatically affects offspring growth performance and meat quality while exploring its epigenetic effects through histone acetylation modulation. After mating, sixty multiparous sows (Landrace × Yorkshire; parity 2-3) were assigned to a 2 × 2 factorial arrangement with inulin (0% vs. 1.5%) and fat (0% or 5%) supplementation until farrowing. Post-weaning, five litters (10 piglets per litter) per treatment were selected and maintained in their original litter for fattening under standardized feeding. The results demonstrated that maternal inulin supplementation during gestation accomplished the following: (1) Increased offspring liver index by 13.4% at weaning and 6.8% at finishing (p < 0.05) while reducing the finishing-phase backfat thickness by 11.6% (p < 0.01), with a significant inulin × fat interaction attenuating fat-induced abdominal lipid accumulation at weaning (p = 0.05). (2) Decreased longissimus dorsi muscle lightness (L*) by 4.5% in finishing pigs (p = 0.02) without altering the other meat quality parameters. (3) Suppressed offspring liver lipid deposition at birth and finishing (p < 0.05), concomitant with upregulated hepatic PGC-1α and CPT1A expression (p < 0.05). (4) Elevated neonatal serum butyrate by 15.6% (p = 0.06) while inhibiting hepatic histone deacetylase (HDAC) activity and enhancing histone H3/H4 acetylation (p < 0.01). These findings suggest that maternal inulin supplementation during gestation mitigates offspring hepatic lipid deposition through butyrate-mediated epigenetic regulation, where microbial-derived butyrate from inulin fermentation inhibits HDAC activity, enhances histone acetylation levels, and upregulates fatty acid β-oxidation gene expression. This study provides novel mechanistic insights into how maternal dietary fiber nutrition programs offspring development through epigenetic reprogramming.

In this study, type-3 resistant starch (RS) with enhanced thermal stability and excellent short-chain fatty acid (SCFA) production was obtained through the butyrylation and subsequent recrystallization at 4 °C of high-amylose maize starch (HAMS). We comprehensively examined and contrasted the structural attributes and in vitro human fecal fermentation behavior of butyrylated RS (BRS) with varying degrees of substitution. Fourier-transform infrared analysis validated the successful integration of carbonyl groups into the starch matrix. This phenomenon was evident through the characteristic peaks at 1727 cm-1. X-ray diffraction and thermal stability analyses delineated the distinct B-type crystalline structure and high relative crystallinity of 25.31 % and 22.23 % of the 10 % and 15 % butyric anhydride BRS-10 and BRS-15, respectively, which differed from that of HAMS. Their second peak gelatinization temperature values reached 95.6 °C and 92.6 °C. The in vitro fermentation of BRS fostered SCFA production, boosting the relative abundance of beneficial bacteria (e.g., Ligilactobacillus and Roseburia). Meanwhile, the extensively modified BRS favored the propagation of Faecalibacterium and Bifidobacterium, maintaining intestinal microbiota advantage. These findings underscore the significant effects of butyrylation modification on fermentation kinetics, metabolite profiles, and gut microbiota composition, providing invaluable insights into the development of functional food products that aim to bolster colonic health.

240 64-week-old Lohman LSL-Lite laying hens were used to evaluate the effect of ahiflower seed (AS) and its press cake (APC) on egg yolk fatty acid profile, production performance, apparent total tract nutrient digestibility (ATTD), egg quality, eggshell mineral content, and fecal microbiota composition for 12 weeks in a completely randomized design, with 6 replicates of 5 birds in a cage. The diets included a control (CD), CD supplemented with 10 % flaxseed (FS), and CD supplemented with AS at 1, 5, and 10 % inclusion levels and APC at 5, 10, and 15 % inclusion levels. Diet did not affect eggshell Ca (P=0.1168) and P (P=0.8212) levels, and feed conversion ratio (P=0.136), but the 10 % FS reduced body weight gain (P=0.044), hen day egg production (P= 0.000) and feed intake (P<.0001) compared to other treatments. The yolk lightness L* was reduced (P=0.030) by 5 % APC compared to 10 % APC, redness a* was reduced (P= 0.002) by 10 % FS and 15 %APC compared to 10 %APC, CD, and 1 % AS. The 10 % FS and 15 %APC also reduced (P<0.001) yellowness *b compared to 1 %AS and 5 %APC. Apparent metabolizable energy (AME) and nitrogen-corrected apparent metabolizable energy (AMEn) increased (P<0.001) in 10 %FS and all AS and APC levels compared to CD. Compared to CD (87 %), ATTD of energy was increased (P<0.001) in hens fed 10 %FS (93 %), 1 %AS (93 %), and 15 %APC (92 %). However, 10 %FS (78.7 %) and 1 %AS (81.7 %) had higher (P=0.011) ATTD of P than 10 %APC (64.6 %). Similarly, ATTD of Ca was reduced (P<0.001) in hens fed 10 %APC compared to CD and 10 %AS. Compared to other treatments, total n-3 and stearidonic acids were increased (P<0.001) by 10 %FS and 10 %AS, respectively, and the total n-6 FAs and linoleic acid were highest (P=0.001) in 15 %APC. Both 10 %AS and 10 %FS increased (P<0.001) eicosapentaenoic, docosahexaenoic, and alpha-linolenic acid, compared to CD. The n-6/n-3 ratio was reduced (P<0.001) by 10 %FS and 10 %AS compared to APC and CD. Dietary treatments modulated fecal microbiota differently, but notably, Lactobacillus was more abundant when hens were fed 5 %AS compared to other treatments. In conclusion, the dietary supplementation of 10 %AS increased n3-FAs deposition in eggs similar to 10 %FS. However, 10 %FS reduced production performance. All levels of AS and APC increased diet metabolizable energy with no negative effect on production performance.

Dietary protein level and amino acid (AA) balance are crucial determinants of animal health and productivity. Supplementing rumen-protected AAs in low-protein diets was considered as an efficient strategy to improve the growth performance of ruminants. The colon serves as a crucial conduit for nutrient metabolism during rumen-protected methionine (RPMet) and rumen-protected lysine (RPLys) supplementation, however, it has been challenging to clarify which specific microbiota and their metabolites play a pivotal role in this process. Here, we applied metagenomic and metabolomic approaches to compare the characteristic microbiome and metabolic strategies in the colon of lambs fed a control diet (CON), a low-protein diet (LP) or a LP diet supplemented with RPMet and RPLys (LR).

The LP treatment decreased the average daily weight gain (ADG) in lambs, while the LR treatment tended to elicit a remission in ADG. The butyrate molar concentration was greater (P < 0.05), while acetate molar concentration (P < 0.05) was lower for lambs fed the LP and LR diets compared to those fed the CON diet. Moreover, the LP treatment remarkably decreased total AA concentration (P < 0.05), while LR treatment showed an improvement in the concentrations of methionine, lysine, leucine, glutamate, and tryptophan. Metagenomic insights proved that the microbial metabolic potentials referring to biosynthesis of volatile fatty acids (VFAs) and AAs in the colon were remarkably altered by three dietary treatments. Metagenomic binning identified distinct microbial markers for the CON group (Alistipes spp., Phocaeicola spp., and Ruminococcus spp.), LP group (Fibrobacter spp., Prevotella spp., Ruminococcus spp., and Escherichia coli), and LR group (Akkermansia muciniphila and RUG099 spp.).

Our findings suggest that RPMet and RPLys supplementation to the low-protein diet could enhance the microbial biosynthesis of butyrate and amino acids, enriche the beneficial bacteria in the colon, and thereby improve the growth performance of lambs.

The current experiment aimed to investigate the effects of sodium butyrate (SB) and vitamin D3 (VD3) supplementation on the growth performance, immune status, antioxidant capacity, and gut health of young broilers under cold stress. A total of 144 1-day-old Arbor Acres chicks were randomly allotted to three treatments with 6 replicates of 8 birds: (1) basal diet; (2) basal diet + cold stress; and (3) basal diet with 1 g/kg SB and 2000 IU/kg VD3 + cold stress. Birds were exposed to cold stress at 16 ± 1 °C for 72 h (d 18-21) and 26 ± 1 °C for the control. The results indicated that the SB/VD3 diet could alleviate the reduction in average daily gain (ADG) caused by cold stress (p < 0.05). The SB/VD3 diet decreased the serum endotoxin level and ileal interleukin-1β gene expression and upregulated interleukin-10 and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression compared with cold-stressed birds (p < 0.05). Furthermore, cold stress altered the composition of gut microbiota, including a decrease in Clostridium_sensu_stricto_1, whereas the SB/VD3 diet prevented the reduction. In conclusion, the SB/VD3 diet mitigated the negative effects of cold stress on growth performance and the intestines by strengthening intestinal barrier function and stabilizing gut microbiota balance in broiler chicks, and these results can help to manage cold stress.

Diabetic retinopathy (DR) is a microvascular complication of diabetes, affecting 34.6% of diabetes patients worldwide. Early detection and timely treatment can effectively improve the prognosis of DR. Metabolomic analysis provides a powerful tool for studying pathophysiological processes. Conducting metabolomic analyses on DR-related biofluids helps identify differential metabolic expressions during disease progression, thereby discovering potential biomarkers to support clinical diagnosis and treatment. Here, an innovative workflow for vitreous liquid analysis is established, and a machine learning-based DR analysis platform integrating vitreous liquid metabolic fingerprint (VL-MF) and plasma metabolic fingerprint (P-MF) derived via nanoparticle enhanced laser desorption/ionization mass spectrometry is developed. Direct VL-MF and P-MF are obtained with desirable reproducibility (coefficient of variation, CV <5%) and remarkable speed (3 s per sample), and DR patients are distinguished from healthy controls applying dual biofluid-MF with an area under the curve (AUC) of 0.957. Moreover, a biomarker candidate panel from vitreous liquid and plasma with an AUC of 0.945 is constructed and the related metabolic pathways are identified by metabolomics pathway analysis (MetPA). This work offers a powerful multi-biofluid platform that can not only contribute to DR but also provide solid references for other clinical applications.

Pectin, a plant-derived polysaccharide, is highly valued for its gelling, thickening, and stabilizing properties, with extensive applications in the food and pharmaceutical industries. This review provides a comprehensive analysis of pectin's structure, categorized by its degree of methyl esterification (DM) and key components, including homogalacturonan (HG) and rhamnogalacturonans (RG-I and RG-II). The influence of diverse extraction methods, such as subcritical water and microwave-assisted techniques, on its structure and functionality is critically examined. Furthermore, the review investigates the absorption, distribution, metabolism, and excretion (ADME) profiles of pectin, emphasizing how structural factors like molecular weight, DM, and neutral sugars impact bioavailability and interactions with gut microbiota. Notably, this review highlights emerging research methodologies, offering novel insights into pectin's pharmacokinetics. By addressing these interrelationships, the review underscores pectin's potential applications in functional foods, personalized nutrition, and targeted therapeutics and identifies key knowledge gaps for future research.

Gout is a prevalent form of inflammatory arthritis that occurs due to high levels of uric acid in the blood leading to the formation of urate crystals in and around the joints, particularly affecting the elderly. Recent research has provided evidence of distinct differences in the gut microbiota of patients with gout and hyperuricemia compared to healthy individuals. However, the link between gut microbiota and age-related gout remained underexplored. Our study found that gut microbiota plays a crucial role in determining susceptibility to age-related gout. Specifically, we observed that age-related gut microbiota regulated the activation of the NLRP3 inflammasome pathway and modulated uric acid metabolism. More scrutiny highlighted the positive impact of 'younger' microbiota on the gut microbiota structure of old or aged mice, enhancing butanoate metabolism and butyric acid content. Experimentation with butyrate supplementation indicated that butyric acid exerts a dual effect, inhibiting inflammation in acute gout and reducing serum uric acid levels. These insights emphasize the potential of gut microbiome rejuvenation in mitigating senile gout, unraveling the intricate dynamics between microbiota, aging, and gout. It potentially serves as a therapeutic target for senile gout-related conditions.

Dietary patterns, such as the Mediterranean diet (MD) and the Western diet (WD), influence gut microbiota composition and functionality, which play important roles in energy metabolism and nutrient absorption.

A descriptive cross-sectional study was designed to evaluate the gut microbiota of 19 Spanish adolescents and to investigate the association of MD and ultra-processed food (UPF) intake with microbial diversity and community structure.

Functional diversity of gut microbiota was evaluated using Biolog EcoPlates, taxonomic composition was assessed with 16S rRNA sequencing via MinION, and phenotypic responses to antibiotics were analyzed using the cenoantibiogram technique under aerobic and anaerobic conditions.

Adolescents with higher adherence to the MD exhibited greater functional diversity, as per the Shannon-Weaver index. In addition, this group showed higher abundance of bacterial genera previously described as beneficial, such as Paraclostridium, Anaerobutyricum, Romboutsia, and Butyricicoccus. In contrast, adolescents reporting greater UPF intakes had a microbiota composition similar to those with low adherence to the MD, characterized by decreased abundance of beneficial genera. Regarding antibiotic resistance, significant differences were only observed under anaerobic conditions, with individuals with low adherence to the MD showing more sensitivity for most antibiotics tested.

These results suggest that the MD promotes a healthier and more balanced gut environment, potentially improving metabolic functions in adolescents. Despite the lack of differences in α-diversity, comparisons of microbial community structure between adolescents following the MD and those with high UPF (characteristic of the WD) showed clear differences in terms of β-diversity. These findings suggest that dietary patterns influence the composition of the gut microbiota in a more complex manner, beyond just taxonomic richness. The outcomes of this exploratory study highlight opportunities for future research to deepen understanding of the long-term health implications of these dietary patterns, as well as the mechanisms regulating the composition, functionality, and phenotypic responses to antibiotics of gut microbial communities.

Patulin (PAT), a foodborne toxin, causes severe intestinal damage. To mitigate this health threat, mice were pretreated with apple polyphenols (AP) in their drinking water (0.01 % and 0.05 %) for eight weeks, followed by exposure to PAT during the last two weeks. Subsequently, histopathological and biochemical evaluations of intestinal tissues were conducted, alongside assessments of alterations in gut microbiota, colonic content metabolome, and hepatic metabolome. Consequently, AP alleviated PAT-induced villus and crypt injury, mucus depletion, GSH level decline, GSH-Px and SOD activity reduction, and MPO activity elevation. Notably, AP counteracted PAT-mediated microbiota disruptions and promoted the abundance of beneficial bacteria (Dubosiella, Akkermansia, Lachnospiraceae, and Lactobacillus). Furthermore, AP counteracted PAT-induced metabolic disorders in the colonic contents and liver. Ultimately, AP prevented intestinal injury by regulating the gut microbiota and amino acid, purine, butanoate, and glycerophospholipid metabolism in the gut-liver axis. These results underscore the potential of AP to prevent foodborne toxin-induced intestinal damage.

The term "gut microbiota" primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual's health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.

Antibiotics, as the most commonly prescribed class of drugs in neonatal intensive care units, have an important impact on the developing neonatal gut microbiota. Therefore, comprehending the effects of commonly used antibiotic therapy on the gut microbiota and butyrate-producers in early infants could provide information for therapeutic decision-making in the NICU.

To explore the effects of antibiotic therapy on the early development of gut microbiota and butyrate-producers in early infants.

A total of 72 infants were included in the study. We performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients who received amoxicillin-clavulanic acid (AC, n = 10), moxalactam (ML, n = 28) and non-antibiotics (NA, n = 34). We then compared the taxonomic composition between treatment regimens, focusing on differences in butyrate-producers.

Our study showed that there were significant differences in Shannon index (p = 0.033) and Beta diversity (p = 0.014) among the three groups. At the family level, compared with the other two groups, the relative abundance of Clostridiaceae (p < 0.001) and Veillonellaceae (p = 0.004) were significantly higher, while the relative abundance of Enterococcidae (p < 0.001) was significantly lower in the NA group. The relative abundance of Enterobacteriaceae (p = 0.022) in the AC group was greater than that in the other two groups. Additionally, butyrate-producers (p < 0.001), especially Clostridiaceae (p < 0.001), were noticeably more abundant in the NA group. The relative abundance of Clostridiaceae and butyrate-producers were the lowest in the ML group (p < 0.001).

We found that antibiotic therapy had an adverse impact on the initial development of gut microbiota and leaded to a reduction in the abundance of butyrate-producers, particularly Clostridiaceae. Furthermore, moxalactam had a more pronounced effect on the gut microbiota compared to amoxicillin-clavulanic acid.

Prior studies have established correlations between gut microbiota (GM) dysbiosis, circulating metabolite alterations, and gastric cancer (GC) risk. However, the causal nature of these associations remains uncertain.

We utilized summary data from genome-wide association studies (GWAS) on GM (European, n=8,956), blood metabolites (European, n=120,241; East Asian, n=4,435), and GC (European, n=476,116; East Asian, n=167,122) to perform a bidirectional Mendelian randomization (MR) analysis, investigating the causal effects of GM and metabolites on GC risk. Additionally, we conducted mediation analysis (two-step MR) to identify potential metabolite mediators in the GM-GC relationship.

We identified twelve negative and seven positive associations between specific GM taxa and GC risk. For blood metabolites, seven traits were found to be significantly associated with reduced GC risk in the European population, with these findings subsequently validated in the East Asian cohort. Three GM taxa showed potential causal associations with five metabolic traits: the Bacteroidia class and Bacteroidales order were positively correlated with five metabolites (all P < 0.013), while Bacteroides OTU97_27 exhibited a negative correlation with one metabolite (P = 0.007). Two-step MR analysis indicated that total lipids in intermediate-density lipoprotein (IDL), IDL particle concentration, phospholipids in medium low-density lipoprotein (LDL), phospholipids in small LDL, and free cholesterol in small LDL indirectly influenced the association between Bacteroidia class/Bacteroidales order and GC, with mediation proportions of 1.71% (P = 0.048), 1.69% (P = 0.048), 2.05% (P = 0.045), 1.85% (P = 0.048), and 1.99% (P = 0.045), respectively.

The present study provides suggestive evidence of a causal relationship between specific GM, blood metabolites, and GC risk, potentially offering new insights into GC etiology.

Butyrate, a short-chain fatty acid, is a crucial product of gut microbial fermentation with significant implications for various metabolic and physiological processes. Dietary sources of butyrate are limited, primarily derived from the fermentation of dietary fibers by butyrate-producing gut bacteria. Butyrate exerts its effects primarily as a histone deacetylase (HDAC) inhibitor and through signaling pathways involving G protein-coupled receptors (GPCRs). Its diverse benefits include promoting gut health, enhancing energy metabolism, and potentially alleviating complications associated with obesity. However, the exact role of butyrate in obesity is still under investigation, with a limited number of human trials necessitating further research to determine its efficacy and safety profile. Moreover, butyrate impact on the gut-brain axis and its modulation of microbiome effect on behavior highlight its broader importance in regulating host physiology. A thorough understanding of the metabolic pathways and mechanisms of butyrate is essential for developing targeted interventions for metabolic disorders. Continued research is crucial to fully realize its therapeutic potential and optimize its clinical applications in human health. In summary, this review illuminates the multifaceted role of butyrate as a potential mediator of obesity and related metabolic changes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder marked by ovarian dysfunction and metabolic abnormality. This study explores the therapeutic potential of leonurine (SCM-198) in PCOS. Our results show that SCM-198 treatment significantly improved ovarian function, hormone disorders and insulin resistance while reducing granulosa cell ferroptosis. This study provides the first evidence that SCM-198 modulates the gut microbiota composition, increases the abundance of Christensenella minuta, and boosts butyrate levels. Transcriptomic and metabolomic analyses revealed that PCOS patients exhibit granulosa cell ferroptosis and decreased butyrate levels in follicular fluid. Butyrate was shown to alleviate ferroptosis in granulosa cells via the SLC7A11/TXNRD1/GPX4 pathway, as confirmed in vitro with KGN cells. The therapeutic mechanism of SCM-198 in the management of PCOS via the gut microbiota-ovary axis involves the enhancement of gut microbiota and its metabolites. This intervention improves ovarian function and alleviates PCOS symptoms by targeting ferroptosis in granulosa cells.