Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probioticsLactobacillus acidophilusNCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated thatLapre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (sem1290·4)v. 4950·9 (sem1689·3) mm³,P < 0·001). Inoculation withLareduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover,Laenhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated withLa(P < 0·05) compared with untreated mice.Lapre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P < 0·05). In addition,Lapre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probioticsLamay play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated thatLamay be associated with modulating the cellular response triggered by colon carcinogenesis.

Infections with intestinal helminth and bacterial pathogens, such as enteropathogenicEscherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminthHeligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacteriumCitrobacter rodentiuminfection, BALB/c and STAT 6 knockout (KO) mice were infected withH. polygyrus,C. rodentium, or both. We found that only BALB/c mice coinfected withH. polygyrusandC. rodentiumdisplayed a marked morbidity and mortality. The enhanced susceptibility toC. rodentiumand intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition,C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promoteC. rodentiuminfection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude thatH. polygyruscoinfection can promoteC. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.

Background: Acute diarrhea is a major cause of childhood morbidity and an economic burden for families. The aim of this study is to explore the effect of probiotics on clinical symptoms, intestinal microbiota, and inflammatory markers during childhood diarrhea. Methods: Children (n = 81) aged six months to six years (mean age 2.31 years) hospitalized for acute diarrhea were randomized to receive probiotics (Lactobacillus casei variety rhamnosus; n = 42) or no probiotics (n = 39) orally twice daily for seven days. Feces samples were also collected to evaluate microbial content using a traditional agar plate and next-generation sequencing. Immunoglobulin A (IgA), lactoferrin, and calprotectin were determined by enzyme-linked immunosorbent assay (ELISA) and compared in different groups. Other clinical symptoms or signs, including fever, vomiting, diarrhea, abdominal pain, bloated abdomen, daily intake, appetite, and body weight were also assessed. Results: Data were collected from 81 individuals across three different time points. Total fecal IgA levels in fecal extracts of the probiotics group were higher than those in the control group, reaching statistical significance (p < 0.05). Concentrations of fecal lactoferrin and calprotectin were significantly downregulated in patients with probiotic Lactobacillus casei variety rhamnosus (Lc) consumption compared to those of the control (p < 0.05). Probiotic Lc administration may be beneficial for gut-microbiota modulation, as shown by the data collected at one week after enrollment. Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotic group. Appetite and oral intake, body-weight gain, abdominal pain, bloating, as well as bowel habits (diarrhea) were much better in children receiving probiotics compared with those in the control group. Conclusion: Fecal IgA increased during acute diarrhea under Lc treatment; in contrast, fecal lactoferrin and calprotectin were downregulated during acute diarrhea under Lc treatment. Probiotic Lc may be a useful supplement for application in children during acute diarrhea to reduce clinical severity and intestinal inflammatory reaction.

Acute infectious diarrhea is a major cause of childhood morbidity and economic burden for families. We evaluate the clinical, microbiologic, and immunologic effects of probiotics in acute infectious diarrhea. Children (n = 304) aged 3 months to 6 years hospitalized for acute diarrhea were randomized to receive Bio-three (a mixture of Bacillus mesentericus, Enterococcus faecalis, and Clostridium butyricum) or placebo orally 3 times daily for 7 days. Fecal samples were homogenized for bacterial culture and blood cells were isolated for cell culture and cytokine analysis. This study is registered (NCT00463190). The mean duration of diarrhea after start of therapy was 60.1 hours in the probiotics group versus 86.3 hours in the placebo group (P = 0.003). Hospital stay was shorter in the probiotics group than in the placebo group (P = 0.009). Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotics (Bio-three) group. IL-10 was increased in the serum and supernatants of cell culture in the probiotics group, and tumor necrosis factor-α values were down-regulated. Interferon-γ and IL-12 were mildly elevated in the probiotics group, compared with the placebo group. This probiotics mixture reduced the severity of diarrhea and length of hospital stay in children with acute diarrhea. In addition to restoring beneficial intestinal flora, probiotics may enhance host protective immunity such as down-regulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines.