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Abstract The interactive pathway of the gut-liver axis underscores the significance of microbiome modulation in the pathogenesis and progression of various liver diseases, including hepatocellular carcinoma (HCC). This study aims to investigate the disparities in the composition and functionality of the hepatic microbiota between tumor tissues and adjacent normal liver tissues, and their implications in the etiology of HCC. We conducted a comparative analysis of the hepatic microbiome between adjacent normal liver tissues and tumor tissues from HCC patients. Samples were categorized according to the modified Union for International Cancer Control (mUICC) staging system into Non-tumor, mUICC stage I, mUICC stage II, and mUICC stage III groups. Microbial richness and community composition were analyzed, and phylogenetic profiles were examined to identify significantly altered microbial taxa among the groups. Predicted metabolic pathways were analyzed using PICRUSt2. Our analysis did not reveal significant differences in microbial richness and community composition with the development of HCC. However, phylogenetic profiling identified significantly altered microbial taxa among the groups. Sphingobium, known for degrading polychlorinated biphenyls (PCBs), exhibited a significantly negative correlation with clinical indices in HCC patients. Conversely, Sphingomonas, a gut bacterium associated with various liver diseases, showed a positive correlation. Predicted metabolic pathways suggested a correlation between atrazine degradation and valine, leucine, and isoleucine biosynthesis with mUICC stage and tumor size. Our results underscore the critical link between hepatic microbial composition and function and the HCC tumor stage, suggesting a potentially pivotal role in the development of HCC. These findings highlight the importance of targeting the hepatic microbiome for therapeutic strategies in HCC.

Abstract Background The association of gut microbiota with cancer etiology and prognosis has been demonstrated in humans and rodents but has not been studied in dogs with different types of tumors. Hypothesis/Objectives To analyze microbiome composition according to tumor progression based on metastasis, recurrence, and therapeutic response in canine tumors. Animals Thirty‐two client‐owned dogs were divided into 3 groups: healthy (n = 9), with lymphoma (n = 12), with nonlymphoid tumors (n = 11). Methods Retrospective case series included animals were divided into subgroups according to the nature and severity of their tumors. Feces were screened for the 16S rRNA gene. Results Overall, alpha diversity was significantly reduced in dogs with tumors (n = 23; 12 lymphoid and 11 nonlymphoid) compared to healthy dogs (n = 9). Bacteroides had lower abundance in canine tumors at genus level. Staphylococcus showed significantly reduced abundance in dogs with aggressive tumor progression. Higher white blood cell (WBC) and neutrophil counts and lower hematocrit were significant in dogs with aggressive tumor. Spearman's rank correlation coefficient analysis revealed several measurements that showed moderate to strong correlations, including Coprococcus with total WBC count, neutrophil count, and hematocrit in the aggressive tumor group, and Saccharimonas with serum albumin and sodium concentration in all tumor dogs. Conclusion and Clinical Importance The diversity of the gut microbiome was significantly reduced in dogs with tumors compared to healthy dogs. Correlations were found between changes in blood measurements and changes in microbiome composition in relation to paraneoplastic syndrome.

Bovine coronavirus (BCoV) is associated with severe diarrhea, dehydration, and depression, which result in significant economic damages in the dairy and beef cattle industries worldwide. However, differences in the gut microbiota structure and their correlations with differing physiological parameters between BCoV-infected calves with diarrhea and recovered calves are not well understood. In this study, fecal specimens were collected from 10 post-weaned calves, before and after 2 months of fluid therapy, and the samples were used for microbiota analysis. Following recovery, the alpha-diversity profiles (observed operational taxonomic units [OTUs], and Chao1, Shannon, and Simpson indices) changed significantly when compared with those of calves with diarrhea. Beta-diversity analysis exhibited significant differences in gut microbiota compositions between calves with diarrhea and those in the recovered state. The abundances of eight phyla and thirteen genera in feces changed markedly after restoration of BCoV diarrhea. In addition, our correlation study clearly revealed that increased abundances of the genera Caproiciproducens, Pseudoflavonifractor, and Oscillibacter negatively correlated with serum glucose, and phosphorus levels, but positively correlated with serum chloride in calves with diarrhea, whereas increased abundances of the genera Peptostreptococcaceae;Clostridium (Clostridium cluster XI), Intestinibacter, Cellulosilyticum, Ruminococcus, Romboutsia, Paeniclostridium, Clostridiaceae;Clostridium and Turicibacter in recovered calves showed the opposite pattern. These results suggest that structural changes of the gut microbiota after recovery from BCoV infection correlate with changes in physiological parameters. In conclusion, our data provide evidence of gut microbiota-composition changes and their correlations with the physical profiles of post-weaned calves, before and after fluid therapy for BCoV-related diarrhea.

Subclinical doses of antimicrobials are commonly used in the swine industry to control infectious diseases and growth performance. Accumulating evidence suggests that swine administered with antibiotics are susceptible to disease development due to disruption of the beneficial gut microbial community, which is associated with host immune regulation, nutrient digestion, and colonization resistance against pathogens. In this study, we found that finishing swine administered with lincomycin showed gut dysbiosis and increased diarrhea incidence compared with control swine. 16S rRNA amplicon sequencing was used to analyze the gut microbiota in finishing swine administered with lincomycin. The relative abundance of detrimental microbes, such as species of Clostridium, Aerococcus, Escherichia-Shigella, and Corynebacterium was increased in the feces of lincomycin-administered finishing swine, but that of bacteria associated with fiber degradation, such as species of Treponema, Succinivibrio, Fibrobacter, and Cellulosilyticum was decreased. Moreover, administration of lincomycin significantly increased the enrichment of metabolic pathways related to pathogenicity and deficiency of polysaccharide degradation. These results suggest that lincomycin treatment could cause severe disruption of the commensal microbiota in finishing swine.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, which can cause severe bone and joint damage. Leuconostoc citreum WiKim56 is a lactic acid bacterium isolated from gatkimchi, fermented mustard leaves. We evaluated the ability of Leu. citreum WiKim56 to modulate T cell responses and suppress RA in a mouse model of collagen-induced arthritis. Leu. citreum WiKim56 lowered the incidence of arthritis, attenuated symptom severity, and inhibited RA progression in the mice. Leu. citreum WiKim56 decreased serum levels of collagen-specific IgG and IgG2a, and reduced the expression of collagen-specific pro-inflammatory cytokines in the spleen and peripheral lymph nodes. Moreover, the proportion and function of regulatory T cells in splenocytes was significantly enhanced by WiKim56 treatment. These data suggest that Leu. citreum ameliorates RA symptoms by suppressing inflammatory responses, and that Leu. citreum WiKim56 may prevent or lessen damage due to inflammatory autoimmune reactions, including those associated with RA.

Lactobacillus sakei WIKIM30 is a Gram-positive facultative anaerobic bacterium isolated from kimchi, a Korean fermented vegetable food. In this study, we found that WIKIM30 promoted regulatory T cell (Treg) differentiation by inducing dendritic cells with tolerogenic properties. The production of the T helper (Th) 2-associated cytokine interleukin (IL)-4 was decreased, but that of the Treg-associated cytokine IL-10 was increased in splenocytes from ovalbumin-sensitized mice treated with WIKIM30. We also investigated the inhibitory capacity of WIKIM30 on the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD), a Th2-dominant allergic disease in mice. Oral administration of L. sakei WIKIM30 significantly reduced AD-like skin lesions and serum immunoglobulin E and IL-4 levels while decreasing the number of CD4+ T cells and B cells and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in peripheral lymph nodes and enhancing Treg differentiation and IL-10 secretion in mesenteric lymph nodes. In addition, WIKIM30 modulated gut microbiome profiles that were altered in AD mice, which showed increases in Arthromitus and Ralstonia and a decrease in Ruminococcus abundance. These changes were reversed by WIKIM30 treatment. Notably, the increase in Ruminococcus was highly correlated with Treg-related responses and may contribute to the alleviation of AD responses. Together, these results suggest that oral administration of L. sakei WIKIM30 modulates allergic Th2 responses enhancing Treg generation and increases the relative abundance of intestinal bacteria that are positively related to Treg generation, and therefore has therapeutic potential for the treatment of AD.