Bao Yi

The growing recognition of the gut microbiota and its associated metabolites as central regulators of host physiology has reshaped our understanding of metabolic disorders. The Research Topic entitled "Advances in Gut Microbiota, Metabolites, and Metabolic Disorders" highlights the multifaceted roles of microbial ecology and metabolite profiling in related diseases. The articles in this collection explore how gut microbiota and its metabolites interact with the host to influence metabolic and immune processes. These metabolic disorders not only include the most common conditions such as obesity and cardiovascular diseases, but also involve some clinical illnesses closely related to various gastrointestinal diseases and metabolic disorders, including rosacea， sudden sensorineural hearing loss, and Helicobacter pylori infection.A central theme emerging from this collection is the identification of disease-associated metabolites alterations and their potential microbial origins. Zhang et al. performed untargeted blood metabolomic analyses across different subtypes of rosacea. Their findings provide important insights into how systemic metabolic alterations distinguish clinical subtypes of rosacea, suggesting that metabolic profiling may aid in disease stratification. Notably, they identified changes in metabolites potentially derived from the gut microbiota, supporting a role of the gut microbiota in inflammatory disease development. Similarly, Ma et al. conducted untargeted plasma metabolomic profiling in patients with sudden sensorineural hearing loss and identified distinct metabolic signatures associated with the condition. In particular, they reported a significant decrease in indole-3-acetamide, a tryptophan-derived metabolites linked to gut microbial metabolism. The authors proposed that the reduced level of indole-3acetamide may contribute to disease pathogenesis through the promotion of inflammation responses. Together, these findings highlight the relevance of microbiotarelated metabolic alterations in disease development.Beyond metabolite-centered findings, this Research Topic further expands the scope to microbial exposure and infection, strengthening the link between microbiota and metabolic health. Liu et al. reported an association between Helicobacter pylori infection and alterations in the apolipoprotein B/ apolipoprotein A1 ratio, suggesting a potential link between microbial exposure and cardiovascular risk. This finding broadens the scope of microbiota-related research beyond commensal microbial communities to include pathogen-associated metabolic consequences.Importantly, beyond observational and associated findings, studies in this collection address whether gut microbiota and their metabolic outputs can be actively modulated to influence disease development. Dong et al. demonstrate that swimming training modulates cecal microbial community and their metabolic outputs in rats fed a high-fat diet, highlighting physical activity as a modifiable factor influencing host-microbiome interactions. Complementing this, Liu et al. showed that electroacupuncture and manual acupuncture exert differential effects on gut microbiota composition and associated metabolic pathways in spontaneously hypertensive rats, providing mechanistic insights into how traditional therapeutic interventions may influence systemic metabolism.These intervention-based studies underscore the transactional potential of targeting microbiota and its metabolites.Collectively, these studies underscore the complex network involving gut microbial community, microbial metabolites, and host responses in metabolism-related disorders. Advancing our understanding in this field may facilitate the identification of novel biomarkers and therapeutic targets. Nevertheless, several challenges remain before these findings can be translated into clinical applications. The heterogeneity of microbiome composition, the dynamic nature of metabolite production, and the difficulty in establishing causal relationships require more integrative approaches. Future studies leveraging multi-omics integration, longitudinal designs, and mechanistic validation will be essential to move from association to intervention.In summary, this Research Topic expands our understanding of the role of gut microbiota and its metabolites across diverse disease contexts. By bridging observational findings with emerging intervention strategies, it provides a foundation for future efforts to harness microbiota-metabolite interactions in the prevention and treatment of metabolic disorders.

Objective: This study investigated the effects of chemically protected sodium butyrate (CSB) on growth performance, serum indicators, rumen fermentation parameters, and microbial communities in Gangba sheep.Methods: Twenty-four healthy 5-month-old male Gangba sheep with an initial body weight of 19.54±1.04 kg were randomly assigned to four groups and fed diets containing 0, 1.0, 5.0, and 10.0 g/kg CSB for 74 days. After a 14-day adaptation period, the daily feed intake of Gangba sheep was measured. Fecal samples were collected during the last 7 days of the trial, and serum and rumen fluid were sampled on the final day.Results: CSB improved final body weight, average daily dry matter intake, and average daily gain while reducing the feed conversion ratio of Gangba sheep (p<0.05). In addition, CSB improved the apparent digestibility of crude protein, dry matter, and neutral detergent fiber (p<0.05). Furthermore, CSB increased serum immunoglobulin G levels while decreasing tumor necrosis factor-α levels (p<0.05). Meanwhile, CSB increased serum growth hormone-releasing hormone levels (p<0.05). Furthermore, CSB increased rumen fluid pH and concentrations of ammonia nitrogen, acetic acid, iso-butyric acid, butyric acid, and total volatile fatty acids, as well as activities of lipase and butyrate kinase (p<0.05). Besides, CSB enhanced the rumen microbiota structure by increasing the relative abundance of Fibrobacter, unclassified Oscillospiraceae, and Ruminococcus.Conclusion: CSB improved immunological and hormone indicators, enhanced the rumen ecological environment, and increased feed digestibility and utilization, thereby promoting the growth of Gangba sheep. It is recommended to use a dosage of 5.0 g/kg dry matter for optimal growth performance and health benefits.

Early intestinal development plays a significant role in determining long-term broiler health and performance; however, information on the effects of new buffer salt-protected sodium butyrate (NBSB) during this stage remains limited. The present study evaluated the early stage effects of NBSB on growth performance, intestinal health, and cecal microbiota, building on our previous 42-day study using ELISA, RT-qPCR, gas chromatography, and 16S rRNA sequencing. In total, 192 day-old male broiler chicks were allocated to three groups using a completely randomized design with eight replicate cages per treatment (eight chicks per cage): (1) a corn soybean basal diet (CTRL), (2) CTRL + 0.01% aureomycin antibiotic (ANBX), and (3) CTRL + 0.08% NBSB. Compared with the CTRL, NBSB increased the final body weight by 6.1%, ADG by 8.0%, and reduced FCR by 5.0% (P < 0.05), with no significant difference from the ANBX group. NBSB also significantly increased IL-10, IgA, IgG, and decreased TNF-α levels (P < 0.05) compared to ANBX. Additionally, NBSB increased villus height (VH) in the ileum and the VH: CD ratio in both the jejunum and ileum (P < 0.05). It further upregulated the expression of tight junction proteins, SOD, and T-AOC/MDA ratio in both intestinal segments, along with T-AOC levels in the jejunum (P < 0.05). NBSB also elevated acetic (AA) and butyric (BA) acid contents in the small and large intestines (P < 0.05). 16S rRNA analysis revealed that NBSB was associated with changes in microbial composition, including significant enrichment of SCFA-producing taxa, such as Ruminococcaceae, Eubacterium_hallii_group, and Ruminococcus (P < 0.05). These associations suggest that NBSB may have potential as a supportive alternative to antibiotics in healthy broilers, although further studies under disease challenge conditions are needed.

High-altitude grazing animals are continuously exposed to strong wind and low temperature, which challenge physiological homeostasis and energy metabolism. Improving living conditions and nutritional supplementation are two commonly used strategies. In this study, sixty 7-month-old Gangba sheep (initial body weight (BW) 21.00 ± 1.90 kg) were allocated to a 42-day trial with four groups (open-air sheepfold, mobile sheepfold, open-air sheepfold + supplementary feeding, mobile sheepfold + supplementary feeding) to investigate their effects on growth performance, serum parameters and gut microbiota in naturally grazing Gangba sheep. Mobile sheepfolds increased the temperature–humidity index (THI) and reducing the wind chill index (WCI) (p < 0.05). The sheep with mobile sheepfold showed higher serum total antioxidant capacity and lower levels of heat shock proteins HSP70 and HSP90 (p < 0.05), indicating alleviated stress. Supplementary feeding markedly increased final BW and average daily gain (p < 0.05). The interaction between sheepfold type and feeding supplementation showed increasing IgA levels in the open-air sheepfold with supplementary feeding group and increasing IL-4 levels in the mobile sheepfold with supplementary feeding group, while TNF-α concentrations were reduced in all three treatment groups (p < 0.05). Meanwhile, KB and FFAs were increased in the open-air sheepfold with supplementary feeding group but decreased in the mobile sheepfold with supplementary feeding group (p < 0.05). The mobile sheepfold also increased the Bacillota-to-Bacteroidota ratio, suggesting improved microbial community structure. Functional predictions showed enrichment of reductive acetogenesis and reduction in aerobic chemoheterotrophy and sulfur-related respiration pathways (p < 0.05). Moreover, key microbial genera were significantly correlated with THI and WCI (p < 0.05). Collectively, these results demonstrated that mobile sheepfold together with feeding supplementation improve stress responses, serum immune and lipid metabolic indicators, and potentially altered gut microbial composition and function, providing insights into host–microbiota interaction in extreme high-altitude environments.

Wheat bran, a significant cereal by-product, is widely used in animal husbandry and the food industry. Our previous study identified a correlation between fiber utilization in Tibetan pigs and their efficient hindgut fermentation capacity. In this study, the Bacillus altitudinis strain Z-99, capable of cellulose degradation, was identified and isolated from Tibetan pigs. The results of solid-state fermentation demonstrated a significant reduction in neutral detergent fiber (NDF), acid detergent fiber (ADF), and hemicellulose content by 12.26 % (P < 0.01), 1.58 % (P < 0.05), and 10.68 % (P < 0.01), respectively, while crude protein content increased by 1.90 % (P < 0.01). Compared to the control group, supplementation with Bacillus altitudinis strain Z-99 enhanced the in vitro fermentation characteristics of wheat bran. In particular, it significantly increased the theoretical maximum gas production (P < 0.05) and elevated the content of acetic acid (P < 0.05), butyric acid (P < 0.05), isobutyric acid (P < 0.01), valeric acid (P < 0.05), and total short-chain fatty acids (P < 0.01). Furthermore, the addition of Bacillus altitudinis strain Z-99 significantly increased the abundance of Bifidobacterium (P < 0.05) and Blautia (P < 0.05), while decreasing the abundance of disease-associated Enterococcus (P < 0.01) and Actinobacillus (P < 0.05). Overall, a Bacillus altitudinis strain Z-99 with cellulose-degrading capacity was isolated from Tibetan pigs, and its functionality was validated through solid-state fermentation and in vitro fermentation methods. This study provided valuable insights into the utilization of wheat bran and the exploration of cellulose-degrading bacteria.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. A total of 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs’ content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI and ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and the VH/CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum were significantly up-regulated in the NSB group. Additionally, SOD (p < 0.05) and the T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05), showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, and serum anti-inflammatory cytokines, and by regulating the intestinal barrier function and antioxidant capacity, SCFAs’ content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

Dihydroquercetin (DHQ) is a natural flavonoid with multiple bioactivities, including hepatoprotective effects. This study aimed to investigate whether DHQ improved lipid dysmetabolism in the body, especially in the liver, and whether there is a relationship between hepatic metabolism and altered gut flora in high-fat diet (HFD)-induced mice. HFD-induced mice were given 50 mg/kg body weight DHQ intragastrically for 10 weeks. The data showed that DHQ reduced body weight, the weight of the liver and white adipose tissue as well as serum leptin, LPS, triglyceride and cholesterol levels. RNA-seq results indicated that DHQ down-regulated lipogenesis-related genes and up-regulated fatty acid oxidation-related genes, including MOGAT1 and CPT1A. Furthermore, DHQ had a tendency to decrease hepatic cholesterol contents by reducing the mRNA levels of cholesterol synthesis genes such as FDPS and HMGCS1. 16S rRNA sequencing analysis indicated that DHQ significantly decreased the richness of Lactococcus, Lachnoclostridium, and Eubacterium_xylanophilum_group. Correlation analysis further demonstrated that these bacteria, Lactococcus and Eubacterium_xylanophilum_group in particular, had significantly positive correlation with lipid and cholesterol synthesis genes, and negative correlation with fatty acid oxidation genes. In conclusion, DHQ could improve hepatic lipid dysmetabolism potentially by improved gut microbial community, which may be used as an intervention strategy in hepatic metabolism diseases.

Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as Cd36, Mogat1, Cyp39a1, Abcc3, and Gpat3. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including Lachnospiraceae, Coriobacteriaceae_UCG-002, Enterorhabdus, Faecalibaculum, and Desulfovibrio. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.

Colitis, a chronic inflammatory bowel disease, is characterized by bloody diarrhea and inflammation in the colon. Lonicera hypoglauca (“Shanyinhua” in Chinese) and Scutellaria baicalensis (“Huangqin” in Chinese) are two traditional Chinese medicinal plants rich in polyphenols, such as chlorogenic acid (CGA) and baicalin (BA), with the effects of anti-inflammation and antioxidation. However, it remains unknown whether extracts from L. hypoglauca and S. baicalensis (LSEs) could mitigate colonic inflammation. In the present study, ICR mice (22.23 ± 1.65 g) were allocated to three groups treated with chow diet without (CON) or with dextran sulfate sodium (DSS) (CON+DSS) in water or LSE supplementation in diet with DSS (LSE+DSS), and then inflammatory and oxidative parameters and colonic microbiota were detected. The results showed that LSE (500 mg/kg) treatment mitigated DSS-induced colitis symptoms and restored the shortened colon length, the increased disease activity index (DAI), and the damaged intestinal barrier. In serum, LSE supplementation significantly decreased levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) and increased IL-10 level. Meanwhile, superoxide dismutase (SOD) and catalase (CAT) were increased, and malondialdehyde (MDA) and reactive oxygen species (ROS) levels were decreased. In the colon tissue, qPCR results showed that LSE supplementation dramatically downregulated the transcriptional expression of IL-1β, IL-6, TNF-α, and MDA and upregulated the expression of SOD1, CAT, and IL-10. Additionally, the damaged gut barriers occludin and zonula occludens-1 (ZO-1) in the CON+DSS group were enhanced with LSE supplementation. Furthermore, LSE treatment regulated the gut microbial communities with higher relative abundance of Dubosiella and Ruminococcus torques group and lower relative abundance of Bacteroides and Turicibacter. Moreover, the contents of short-chain fatty acids (SCFAs) as products of gut microbiota were also increased. Correlation analysis showed that the mRNA expression of SOD1 was negatively correlated with TNF-α (r = -0.900, P < 0.05); the mRNA expression of IL-6 (r = -0.779, P < 0.05) and TNF-α (r = -0.703, P < 0.05) had a dramatically negative correlation with Dubosiella. In conclusion, LSE supplementation could effectively ameliorate inflammation by modulating oxidative stress and gut microbiota in a colitis mouse model.