The onset and progression of type 2 diabetes mellitus (T2DM) are strongly associated with imbalances in gut bacteria, making the gut microbiome a new potential therapeutic focus. This commentary examines the recent publication in World Journal of Diabetes. The article explores the association between T2DM and gut microbiota, with a focus on the pathophysiological changes related to dysbiosis. It proposes innovative microbiome-targeted therapeutic strategies and evaluates the challenges and future directions of such approaches. This editorial summarizes the key points of their discussion of the role of the gut microbiome in T2DM and elaborates on the influence of specific gut microbial species on the disease through the host-microbiota metabolic axis. It provides new insights for future research on gut-microbiota-based interventions for T2DM.

Acute liver failure is a drastic, unpredictable clinical syndrome with high mortality. Various preventive and adjuvant therapies based on modulating the gut flora have been proposed for hepatic injury. We aimed to explore the preventive and therapeutic effects of Bifidobacterium adolescentis CGMCC15058 on rat liver failure, as well as the potential microecological and immunological mechanisms of those effects. B. adolescentis CGMCC15058 (3 × 10⁹ CFU), isolated from healthy human stool, was gavaged to Sprague-Dawley rats for 14 days. Acute liver injury was induced on the 15th day by intraperitoneal injection of D-galactosamine. After 24 h, liver and terminal ileum histology, liver function, plasma cytokines, bacterial translocation and gut microbiota composition were assessed. We found that pretreatment with B. adolescentis significantly relieved elevated serum levels of alanine aminotransferase (ALT), total bile acid and lipopolysaccharide-binding protein and enhanced the expression of mucin 4 and the tight junction protein zonula occludens-1. B. adolescentis exhibited anti-inflammatory properties as indicated by decreased levels of mTOR and the inflammatory cytokines TNF-α and IL-6, as well as elevated levels of the anti-inflammatory cytokine interleukins-10 in the liver. Similar anti-inflammatory signs were also found in plasma. B. adolescentis significantly altered the microbial community, depleting the common pathogenic taxon Proteus and markedly enriching the taxa Coriobacteriaceae, Bacteroidales and Allobaculum, which are involved in regulating the metabolism of lipids and aromatic amino acids. Our findings not only suggest B. adolescentis acts as a prospective probiotic against liver failure but also provide new insights into the prevention and treatment of liver disease.

The intestinal microbiome has been the intense focus of recent study, but how the microbiota affects connected organs, such as the liver, has not been fully elucidated. The microbiome regulates intestinal permeability and helps to metabolise the human diet into small molecules, thus directly affecting liver health. Several studies have linked intestinal dysbiosis to the severity and progression of liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, primary sclerosing cholangitis, total parenteral nutrition-associated liver disease, and cystic fibrosis-associated liver disease. However, there is limited information and interpretation with regard to how the microbiome could contribute to liver disease in the paediatric population. Notably, the gut microbiota is distinct at birth and does not establish an adult profile until the third year of life. Clinical research suggests that paediatric liver disease differs in both severity and rate of progression compared with adult forms, suggesting independent mechanisms of pathogenesis. We discuss data linking the intestinal microbiome to liver disease development and therapeutic efforts to modify the microbiome in children.

To investigate the hypothesis that an oral supplementation of Bifidobacterium adolescentis protects against a diet-induced nonalcoholic steatohepatitis in a mouse model, C57BL/6 mice were fed either a Western-style or a control diet±tap water fortified with B. adolescentis (5×10(7) cfu/ml) ad libitum for 12 weeks. Mice fed a Western-style diet gained significantly more weight than mice fed a control diet and developed a mild steatohepatitis. Western-style diet fed groups concomitantly treated with B. adolescentis had significantly decreased liver damage, whereas portal endotoxin levels and toll-like receptor-4 protein levels as well as myeloid differentiation factor 88 mRNA were increased in livers of both Western-style diet fed groups. The protective effects of the B. adolescentis were associated with a significant attenuation of the formation of reactive oxygen species, activation of nuclear factor κB (NFκB) and induction of markers of inflammation in the liver. Taken together, our data suggest that an oral supplementation of the B. adolescentis attenuates diet-induced steatohepatitis, and this effect is associated with prevention from lipid peroxidation, NFκB activation and finally inflammation in the liver.

Intestinal microbiota of infants differ in response to gestational age, delivery mode and feeding regimen. Dietary supplementation of probiotic bacteria is one method of promoting healthy populations. We examined the impact of a novel probiotic strain of Bifidobacterium longum (AH1206) on the health, growth and development of neonatal pigs as a model for infants. Day-old pigs were fed milk-based formula containing AH1206 at 0, 10⁹, or 10¹¹ CFU/d for 18 d (n=10/treatment). Differences were not detected in growth, organ weights or body temperatures (P>0.1); however pigs fed the high dose showed a small (2%) reduction in feed intake. Bacterial translocation was not affected as indicated by total anaerobic and aerobic counts (CFU) in samples of spleen, liver and mesenteric lymph nodes (P>0.1). Feeding AH1206 had no effects on fecal consistency, but increased the density of B. longum in the cecum. Ileal TNF expression tended to increase (P=0.08) while IL-10 expression increased linearly (P=0.01) with supplementation. Based upon findings in the suckling piglet model, we suggest that dietary supplementation with B. longum (AH1206) may be safe for human infants based on a lack of growth, development or deleterious immune-related effects observed in piglets.

The present study aimed to determine whether any specific intestinal site or intestinal mucosal inflammation is highly correlated with bacterial translocation (BT). Enterostomy tubes were surgically placed in adult male Sprague-Dawley rats 5 days before induction of experimental model. After surgery, sterile water containing kanamycin (25 mg/L) was injected into each intestinal segment through the tubes for 3 days. Green fluorescent protein (GFP)-transfected Escherichia coli (n = 30 for lipopolysaccharide (LPS) group, and n = 30 for control group) or 0.9 % saline (n = 30 for blank group) were injected into each intestinal segment through the tubes for two consecutive days. Rats were then subjected to LPS-induced endotoxemia; lactulose and mannitol were injected into each intestinal segment through the tubes simultaneously. At 6 h after LPS injection, BT to distant organs and integrity of tight junctions (TJ) were examined by fluorescence and electron microscopy, respectively. The urinary excretion ratio of lactulose/mannitol (L/M) and intestinal mucosal cytokine levels were assessed. We found that the intestinal permeability, reflected by translocation rates of GFP-labeled E. coli, the levels of open TJ, the excretion ratio of L/M, and the inflammatory cytokine levels were higher in the LPS group than in the control and blank groups. The endotoxemia ileum showed the highest levels of both intestinal permeability and inflammatory cytokine, while the colon showed the lowest. The present study of endotoxemia rats suggests that LPS increases gut paracellular permeability and induces BT. The ileum is the site of greatest BT risk, while the colon is the lowest, and the difference in risk between these sites is correlated with intestinal mucosal inflammation.

The authors aimed to investigate the role of anti-tumor necrosis factor (TNF)-α monoclonal antibody treatment in a mouse model of parenteral nutrition-associated liver disease (PNALD).

C57BL/6J male mice (aged 6-8 weeks) were randomly assigned to 3 groups: parenteral nutrition (PN), PN with anti-TNF-α monoclonal antibody treatment (PN + mAb), and controls. A central venous catheter was inserted for intravenous infusion of a PN solution (PN and PN + mAb groups) or saline (controls) for 7 days. Liver pathology, hepatic biochemical indicators, and serum TNF-α concentrations were analyzed. Levels of hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA were also evaluated in each group.

The PN group showed significant increases in serum transaminase, direct bilirubin, and bile acids relative to the control group (P < .05). Histopathological changes in this group were consistent with early stage cholestasis. The pathological score and serum alanine aminotransferase, total bilirubin, and direct bilirubin levels were improved in the PN + mAb group relative to the PN group (P < .05). The PN group showed significantly lower hepatic bsep, mdr1a/mdr1b, mdr2, and mrp2 mRNA expression than the controls (P < .05), but these were significantly increased compared to the PN group (P < .05).

Infliximab administered at a single dose of 5 mg/kg body weight ameliorated the progression of PNALD and improved the expression of hepatic ABC transporter genes. Therefore, anti-TNF-α monoclonal antibody may be a beneficial therapy for patients with PNALD.

The aim of the present study was to investigate the effects of Bifidobacterium adolescentis (Bif) supplementation on visceral fat accumulation and insulin sensitivity of the metabolic syndrome in HF-diet-fed rats. Adult male Wistar rats (n 10 per group) were fed four different experimental diets for 12 weeks as follows: standard diet; high-fat (HF) diet; a mix of HF diet and Bif; a mix of standard diet and Bif. Liver, mesenteric fat, epididymal fat, retroperitoneal fat, and inguinal fat, pancreas and triceps surae in all four groups of the rats were weighed, while liver steatosis and insulin sensitivity were evaluated at the end point of the study. As the number of intestinal Bifidobacterium species decreased obviously, fat pad weight and body weight increased significantly in the HF group compared with in the other three groups (P <0·05). Addition of Bif led to a reduction in body weight and fat pad weight (P <0·05). With an increase in liver weight, more severe steatosis of hepatocytes was observed in the HF group compared with in the other three groups. A significant decrease of the glucose infusion rate and pancreas weight was found in the HF group (P <0·05). This deleterious effect was alleviated when Bif was added to the diets. Bifidobacterium supplementation ameliorated visceral fat accumulation and insulin sensitivity of the metabolic syndrome in HF-diet-fed rats.

Recent evidence suggests that intestinal Bifidobacterium species (spp.) positively correlates with improved insulin resistance and obesity, and this might be linked to metabolic inflammation. The expression of intestinal REG (regenerating) family proteins which are widely involved in inflammatory bowel disease and diabetes are still unknown in metabolic syndrome. Hence, we investigated the effects of Bifidobacterium longum (BIF) supplementation on metabolic parameters, intestinal function and expression of Reg family genes in a rat model of metabolic syndrome induced by a high-fat (HF) diet. We specifically increased the gut bifidobacterial content of HF-fed rats through BIF supplementation. Compared with the normal chow-fed control rats, HF feeding significantly reduced intestinal Bifidobacterium. As expected, BIF supplementation fed rats had totally restored quantities of Bifidobacterium. HF diet-fed rats showed significant increase in body weight, fat deposits, systolic blood pressure, fasting glucose, fasting triglycerides and reduced insulin sensitivity, while increases of intestinal Bifidobacterium did improve HF-diet-induced metabolic disorders. HF feeding led to significantly higher levels of the plasma lipopolysaccharide, interleukin-1β and intestinal myeloperoxidase, as well as intestinal inflammatory activity index, while these parameters were normalized to the control levels in the HF + BIF-treated rats. The levels of RegI mRNA and protein in the HF + BIF group were significantly higher than the control and the HF groups. Increasing Bifidobacterium in the gut improved HF-fed-induced metabolic syndrome by reducing metabolic endotoxin concentrations and intestinal inflammation, as well as upgrading the expression of intestinal Reg I as a regulator of growth factor.