Ulcerative colitis (UC) is characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options. Here, we demonstrate that Lactobacillus delbrueckii is commonly reduced in low-birth-weight piglets, dextran sulfate sodium (DSS)-induced colitis mice, and UC patients. L. delbrueckii and its surface proteins mitigate intestinal inflammation in a macrophage-dependent manner. We further identify P4430, a DUF4430-domain-containing protein, as a key surface protein that protects against intestinal inflammation by suppressing M1 polarization and downregulating inflammatory responses of macrophages. Mechanistically, P4430 reduces inflammation by binding to and inhibiting Mincle, a C-type lectin receptor. These findings elucidate a key effector molecule of L. delbrueckii in modulating inflammatory responses and highlight the therapeutic potential of commensal bacteria and their cellular components in treating UC and possibly other intestinal inflammatory diseases.

BACKGROUND:The rising global incidence of inflammatory bowel disease (IBD) underscores the pressing demand for effective therapeutic approaches. Among promising next-generation probiotics (NGPs), certain Bacteroides species, notably Bacteroides cellulosilyticus, have attracted increasing interests. However, their mechanisms of action remain incompletely elucidated. METHODS:Six Bacteroides strains were isolated from porcine intestine, among which B. cellulosilyticus LYH2 was selected for detailed functional characterisation. Genomic and metabolic profiling were conducted to evaluate its polysaccharide-degrading capacity, short-chain fatty acid (SCFA) production, and antimicrobial metabolite synthesis. In vitro and in vivo studies assessed its dose-dependent effects on pathogen inhibition, macrophage infection, immune modulation, and metabolic safety. A dextran sulphate sodium (DSS)-induced colitis model (male C57BL/6J mice), along with Ffar3-deficient mice, was employed to investigate anti-inflammatory efficacy and underlying mechanisms. FINDINGS:B. cellulosilyticus LYH2 demonstrated broad-spectrum antimicrobial activity, effectively suppressed macrophage infection, and reduced pro-inflammatory gene expression in vitro. Long-term oral administration proved safe in mice and improved metabolic parameters. In DSS-induced colitis, B. cellulosilyticus LYH2 outperformed a reference Bacteroides strain, mesalamine, and Lactobacillus reuteri in mitigating inflammation and restoring colonic goblet cell numbers. Mechanistically, B. cellulosilyticus LYH2 enhanced colonic propionate production, modulated gut microbiota composition, and activated Ffar3 signalling, consequently attenuating M1 macrophage polarisation. Genetic ablation of Ffar3 largely abolished these protective effects. INTERPRETATION:B. cellulosilyticus LYH2 represents a safe and functionally potent NGP that alleviates experimental colitis via propionate-Ffar3 signalling, supporting its therapeutic potential for intestinal inflammatory disorders. FUNDING:This research was supported by grants from National Natural Science Foundation of China (32372900) and Natural Science Foundation of Sichuan Province (2023NSFSC0237).

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by immunological dysregulation and microbial dysbiosis in the colon. Although D-mannose has emerged as a promising candidate for the amelioration of UC, the underlying mechanisms remain incompletely defined. This study investigated the regulatory role of D-mannose in the gut microbiota-host gene axis in murine colitis and delineated the key signaling pathways involved. The results demonstrated that D-mannose markedly ameliorated colitis in mice, concomitant with obvious remodeling of the gut microbial ecosystem, as evidenced by altered α-diversity and β-diversity, an elevated gut microbiota health index, and a reduced dysbiosis index. Notably, the microbial taxa most responsive to D-mannose comprise Akkermansia muciniphila, Limosilactobacillus reuteri, and Lactobacillus johnsonii. Transcriptomic profiling revealed that D-mannose impeded the expression of ten hub genes (Il6, Mmp9, Ccl2, Fgf2, Cxcl1, Ptgs2, Il1β, Timp1, Cxcl5, and Spp1), which were upregulated in colonic tissue following DSS exposure. The abundance of A. muciniphila, L. reuteri, and L. johnsonii exhibited a negative correlation with the expression levels of Il6, Il1β, Ccl2, Mmp9, Timp1, Fgf2, Ptgs2, and Spp1. Enrichment analysis revealed the PI3K/AKT signaling pathway as a vital regulatory route in the D-mannose-driven mitigation of colitis. In vitro experiments on RAW264.7 macrophages indicated that D-mannose suppressed lipopolysaccharide-induced activation of AKT and its downstream NF-κB, resulting in a decrease in the expression of pro-inflammatory cytokines Il1β and Il6. The molecular docking results further validated the molecular interaction between D-mannose and AKT. In summary, D-mannose ameliorates DSS-induced colitis by reshaping the gut microbiota-host gene axis and restraining PI3K/AKT/NF-κB signaling. These findings offer novel mechanistic insights into the role of D-mannose in mitigating colonic inflammation, underscoring its potential as a dietary intervention for ulcerative colitis.

Methanogens, strictly anaerobic archaea within the gut microbiota of monogastric animals, play dualistic roles in host health through their unique molecular and metabolic characteristics. Distinguished by conserved 16S rRNA sequences, ether-linked membrane lipids, and archaea-specific cofactors (e.g., Coenzymes M and F420), these microorganisms drive methanogenesis via hydrogenotrophic, aceticlastic, and methylotrophic pathways. Despite their low abundance (~1%–10% of gut anaerobes), methanogens critically regulate the host's metabolic homeostasis by scavenging hydrogen to enhance fibrolytic bacterial activity, improving dietary fiber degradation and nutrient absorption. However, their overgrowth correlates with metabolic disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and chronic constipation, underscoring a functional duality. Host-specific distribution patterns reveal the dominance of Methanobrevibacter smithii in humans and pigs, while Methanomassiliicoccales and Methanosphaera occupy niche roles in rabbits and companion animals. Their abundance is shaped by developmental stages (e.g., maternal transmission, post-weaning shifts), dietary fiber intake, physiological states (e.g., IBD-linked reduction, IBS/obesity-associated proliferation), and environmental stressors (e.g., ammonia tolerance). Current research limitations include bacterial-centric biases, undefined pathogenic thresholds, and scarce cross-species comparisons. Future directions emphasize multi-omics integration to elucidate methanogen–host interactions, develop 'archaebiotics' for targeted population modulation, and engineer ecological strategies (e.g., enhancing hydrogen sinks) to mitigate methane-related disorders. Advancing this knowledge will optimize therapeutic interventions for metabolic diseases, improve nutrient utilization, and reduce environmental methane emissions.

This study employed a porcine model to investigate the dynamic effects of inulin (INU) and microcrystalline cellulose (MCC) on the profiles of intestinal short-chain fatty acids (SCFAs) and the composition of rectal fungal communities. Twenty-four healthy growing pigs were randomly allocated to three groups: a control group (CON), a 5

Background: Glutamate, a nutritionally non-essential amino acid, is a key intermediate in nitrogen metabolism. Despite more studies on its functional role in intestine health, it remains unknown how glutamate regulates nitrogen metabolism in animals fed a low-protein diet. Methods: Herein, we investigated the effects of glutamate supplementation on colonic amino acid transport, barrier protein expression, microbiota alterations, fecal nitrogen emissions, hepatic amino acid transport, and protein synthesis in weaned rats. Results: We found that protein restriction diminished the mucus thickness, reduced goblet cell numbers, and the expression of EAAT3, y+LAT2 in the colon. In contrast, glutamate supplementation reversed these effects, increasing the colon length and enhancing the expression of ZO-1, Occludin, and Claudin-1 in the colon. At the genus level, glutamate increased the abundance of Lactococcus and Clostridia_sensu_stricto_18. Additionally, glutamate supplementation resulted in an increased apparent nitrogen digestibility, reduced the ratio of fecal nitrogen to total nitrogen intake, and increased the ratio of fecal microbial nitrogen to total nitrogen intake. Protein restriction decreased the mRNA level of ATP1A1, EAAT3, SNAT9/2, and ASCT2, and the protein level of p-mTOR, mTOR, p-mTOR/mTOR, and p-p70S6K/p70S6K as well as p-4EBP1/4EBP1 in the liver. These effects were reversed by glutamate supplementation. Conclusions: In conclusion, glutamate supplementation upregulates amino acid transporters and barrier protein expression in the colon, modulates microbiota composition to reduce fecal nitrogen excretion, and enhances amino acid transport and protein synthesis in the liver by activating the mTOR/p70S6K/4EBP1 pathway, which influences nitrogen metabolism in weaned rats fed a low-protein diet.

Intrauterine growth restriction (IUGR) commonly occurs in pigs and poses a significant challenge to the swine industry. This study investigated the effect of fermented milk on growth performance and intestinal health in IUGR-affected piglets. A total of 24 28-day-old weaned piglets with IUGR were randomly assigned to a corn-soybean basal diet (control) or a basal diet mixed with fermented milk (3:1 w/v, treatment). The results showed that fermented milk increased the average daily gain and decreased the feed-to-gain ratio (p < 0.05). Fermented milk increased the villus height in the duodenum and decreased the jejunal crypt depth (p < 0.05). Pigs in the treatment showed higher activities of lipase, α-amylase, and sucrase in the duodenum, along with an elevation in jejunal sucrase activity (p < 0.05). The ileal glutathione concentration was increased by the treatment (p < 0.05). Moreover, fermented milk upregulated the protein expression of occludin and claudin-3 while decreasing the gene expression of interleukin 1 beta, interleukin 6, and tumor necrosis factor αlpha in the jejunum (p < 0.05). Collectively, these results indicate that dietary supplementation with fermented milk significantly improved growth performance through the enhancement of intestinal functions in IUGR piglets, highlighting the potential of fermented milk as a nutritional strategy to improve postnatal growth in IUGR piglets.

Intestinal fungi, collectively referred to as mycobiota, constitute a small (0.01–2%) but crucial component of the overall intestinal microbiota. While fungi are far less abundant than bacteria in the gut, the volume of an average fungal cell is roughly 100-fold greater than that of an average bacterial cell. They play a vital role in nutrient metabolism and maintaining intestinal health. The composition and spatial organization of mycobiota vary across different animal species and are influenced by a multitude of factors, including age, diet, and the host’s physiological state. At present, quantitative research on the composition of mycobiota in monogastric animals remains scarce, and investigations into the mechanisms underlying their metabolic functions are also relatively restricted. This review delves into the distribution characteristics of mycobiota, including Candida albicans, Saccharomyces cerevisiae, Kazachstania slooffiae, in monogastric animals, the factors influencing their composition, and the consequent impacts on host metabolism and health. The objective is to offer insights for a deeper understanding of the nutritional significance of intestinal fungi in monogastric animals and to explore the mechanisms by which they affect host health in relation to inflammatory bowel disease (IBD), diarrhea, and obesity. Through a systematic evaluation of their functional contributions, this review shifts our perception of intestinal fungi from overlooked commensals to key components in gut ecosystem dynamics, emphasizing their potential in personalized metabolic control regulation and the enhancement of disease prevention and treatment strategies.

Grape seed proanthocyanidin (GSP) is a type of plant polyphenol with a wide variety of biological activities, such as antioxidant properties. This study investigated the effects of GSP supplementation on growth performance and meat quality in growing-finishing pigs. A total of 180 pigs (with an initial average body weight of 30.37 +/- 0.66 kg) were randomly assigned to five treatments: a control diet or a control diet supplemented with GSP at 15, 30, 60, and 120 mg/kg. Each treatment group comprised six replicate pens (6 pigs per pen). Results showed that GSP supplementation linearly increased the average daily gain (P = 0.048) and quadratically decreased the feed intake to gain ratio (P = 0.049) with the lowest values at 30 and 60 mg/kg GSP. Serum concentrations of immunoglobulins (Ig) (IgA, IgG, IgM), total antioxidative capacity, catalase, and total superoxide dismutase were elevated with the peak levels at 30 mg/kg GSP (P < 0.05). Serum glutathione peroxidase increased and malondialdehyde decreased quadratically (P < 0.05), with peak and trough levels at 120 and 60 mg/kg GSP, respectively. The GSP also improved dressing percentage and muscle redness (a & lowast;(45 min)) with optimal levels at 30 and 60 mg/kg (P < 0.05). Additionally, GSP supplementation quadratically reduced the muscle yellowness (b & lowast;(24 h)) and shear force (P < 0.05), with the lowest values at 120 mg/kg. The expression level of myosin heavy chain I in muscle was quadratically increased with maximum expression at 30 and 60 mg/kg (P = 0.015). Furthermore, the expression levels of fatty acid synthase, phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase in the muscle were decreased quadratically (P < 0.05) with the lowest values at 120 mg/kg. Additionally, GSP supplementation at 60 mg/kg upregulated the expression of hepatic hormone-sensitive triglyceride lipase and PEPCK (P < 0.05). These results suggest that GSP enhances carcass characteristics and meat quality in growing-finishing pigs, potentially through improved antioxidative capacity, modified muscle fiber type distribution, and altered glucose-lipid metabolism in muscle and liver. (c) 2025 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

Lactobacillus species have been shown to alleviate gut inflammation and oxidative stress. However, the effect of different lactobacilli components on gut inflammation has not been well studied. This study aims to identify the differences in the effect and mechanisms of different forms and components of Limosilactobacillus mucosae (LM) treatment in the alleviation of gut inflammation using a colitis mouse model that is induced by dextran sodium sulfate (DSS). Seventy-two C57BL/6 mice were divided into six groups: control, DSS, live LM+DSS (LM+DSS), heat-killed LM+DSS (HKLM+DSS), LM cell-free supernatant + DSS (LMCS+DSS), and MRS medium + DSS (MRS+DSS). The mice were treated with different forms and components of LM for two weeks before DSS treatment. After that, the mice were sacrificed for an assessment of their levels of inflammatory cytokines, serotonin (5-HT) receptors (HTRs), and tryptophan metabolites. The results showed that, compared to other treatments, LMCS was more effective (p < 0.05) in the alleviation of DSS-induced body weight loss and led to an increase in the disease activity index score. All three forms and components of LM increased (p < 0.05) the levels of indole-3-acetic acid but reduced (p < 0.05) the levels of 5-HT in the colon. HKLM or LMCS reduced (p < 0.05) the percentages of CD3+CD8+ cytotoxic T cells but increased (p < 0.05) the percentages of CD3+CD4+ T helper cells in the spleen. LM or HKLM increased (p < 0.05) abundances of CD4+Foxp3+ regulatory T cells in the spleen. The LM and LMCS treatments reduced (p < 0.05) the expression of the pro-inflammatory cytokines Il6 and Il17a. The mice in the HKLM+DSS group had higher (p < 0.05) mRNA levels of the anti-inflammatory cytokine Il10, the cell differentiation and proliferation markers Lgr5 and Ki67, the 5-HT degradation enzyme Maoa, and HTRs (Htr1a, Htr2a, and Htr2b) in the colon. All three forms and components of LM reduced the phosphorylation of STAT3. The above findings can help to optimize the functionality of probiotics and develop new dietary strategies that aid in the maintenance of a healthy gut.

Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected phytochemicals and Trp metabolites on the ion transport and 5-HT metabolism and signaling in the ileum of mice in vitro using the Ussing chamber technique. During the in vitro incubation, vanillylmandelic acid (VMA) reduced (p < 0.05) the short-circuit current, and 100 μM chlorogenic acid (CGA) (p = 0.12) and perillic acid (PA) (p = 0.14) had a tendency to reduce the short-circuit current of the ileum. Compared with the control, PA and N-acetylserotonin treatment upregulated the expression of tryptophan hydroxylase 1 (Tph1), while 100 μM cinnamic acid, indolelactic acid (ILA), and 10 μM CGA or indoleacetaldehyde (IAld) treatments downregulated (p < 0.05) the mRNA levels of Tph1. In addition, 10 μM IAld or 100 μM ILA upregulated (p < 0.05) the expression of monoamine oxidase A (Maoa). However, 10 μM CGA or 100 μM PA downregulated (p < 0.05) Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p < 0.05) the expression of Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p < 0.05) the ratios of Htr1a/Htr7 and Htr4/Htr7. These findings may help to elucidate the effects of phytochemicals and Trp metabolites on the regulation of gut ion transport and 5-HT signaling-related gut homeostasis in health and disease.

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

Backgrounds The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. Results In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. Conclusion These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-β-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development. Graphical Abstract

Background: Intrauterine growth restriction (IUGR) resulted in high mortality and many physiological defects of piglets, causing huge economic loss in the swine industry. Lactobacillus amylovorus (L. amylovorus) was identified as one of the main differential bacteria between IUGR and normal piglets. However, the effects of L. amylovorus on the growth performance and intestinal health in IUGR piglets remained unclear. Objectives: This study aimed to investigate the promoting effects of L. amylovorus Mafic1501, a new strain isolated from normal piglets, on the growth performance and intestinal barrier functions in IUGR piglets. Methods: Newborn mice or piglets were assigned into 3 groups: CON (normal birth weight, control), IUGR (low birth weight), and IUGR thorn L. amy (low birth weight), administered with sterile saline or L. amylovorus Mafic1501, respectively. Growth performance, lactose content in the digesta, intestinal lactose transporter, and barrier function parameters were profiled. IPEC-J2 cells were cultured to verify the effects of L. amylovorus Mafic1501 on lactose utilization and intestinal barrier functions. Results: L. amylovorus Mafic1501 elevated body weight and average daily gain of IUGR mice and piglets (P < 0.05). The lactose content in the ileum was decreased, whereas gene expression of glucose transporter 2 (GLUT2) was increased by L. amylovorus Mafic1501 in IUGR piglets during suckling period (P < 0.05). Besides, L. amylovorus Mafic1501 promoted intestinal barrier functions by increasing the villus height and relative gene expressions of tight junctions (P < 0.05). L. amylovorus Mafic1501 and its culture supernatant decreased the lactose level in the medium and upregulated gene expressions of transporter GLUT2 and tight junction protein Claudin-1 of IPEC-J2 cells (P < 0.05). Conclusion: L. amylovorus Mafic1501 improved the growth performance of IUGR piglets by promoting the lactose utilization in small intestine and enhancing intestinal barrier functions. Our results provided the new evidence of L. amylovorus Mafic1501 for its application in the swine industry.

Tryptophan (Trp) has been shown to regulate immune function by modulating gut serotonin (5-HT) metabolism and signaling. However, the mechanisms underlying the microbial modulation of gut 5-HT signaling in gut inflammation with gut microbiota dysbiosis require further investigation. Here, we investigated the effects of Trp supplementation on the composition and metabolism of the gut microbiome and 5-HT signaling-related gut immune function using a dextran sodium sulfate (DSS)-induced colitis mouse model coupled with antibiotic exposure. The results showed that antibiotic treatment before but not during DSS treatment decreased the immunoregulatory effects of Trp and aggravated gut inflammation and body weight loss in mice. Metagenomic analysis revealed that the fecal microbiota transplantation of Trp-enriched gut microbiota to recipient mice subject to antibiotic pre-exposure and DSS treatment alleviated inflammation by increasing the relative abundances of Lactobacillus and Parabacteroides and the microbial production of indole coupled with the activation of the 5-HT receptor 2B (HTR2B) in the colon. Transcriptomic analysis showed that HTR2B agonist administration strengthened the beneficial effects of Trp in DSS-induced colitis mice with antibiotic exposure by reducing gut lipopolysaccharide-binding protein (LBP) production, IκB-α/nuclear factor-κB signaling, and M1 macrophage polarization. Indole treatment reduced LBP production and M1 macrophage polarization both in mice with DSS-induced colitis and in lipopolysaccharide-treated mouse macrophages; however, the HTR2B antagonist reversed the effects of indole. Our findings provide the basis for developing new dietary and therapeutic interventions to improve gut microbiota dysbiosis-associated inflammatory gut disorders and diseases.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-kappa B activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders. Here, Yujun Wu and colleagues report that a synbiotic composed of galactooligosaccharides and Limosilactobacillus reuteri alleviates gut inflammation in animals by enriching pentadecanoic acid synthesis from Bacteroides acidifaciens, showing potential for treating ulcerative colitis.

Background: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life.Objectives: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice.Methods: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and in-flammatory cytokines such as IL-1 & beta;, TNF-& alpha; , IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation.Results: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly down-regulated. IL-1 & beta; and TNF-& alpha; were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b thorn CD16/32 thorn M1 macrophages (P < 0.05) and fewer CD206 thorn M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexoki-nase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). Conclusions: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of in-testinal inflammation in LBW animals.