Search

Antibiotic therapy may have important side effects. Guidelines recommend the administration of specific probiotics to reduce the risk of antibiotic-associated diarrhoea (AAD). The rates and determinants of antibiotics and co-prescription of probiotics in children remain poorly known in Asia-Pacific countries, which are very heterogenous in terms of economic development, health care organization and health policies. A survey among general practitioners (GPs) and paediatricians was performed in seven countries of the Asia-Pacific area (Australia, Japan, Indonesia, India, China, Singapore, and South Korea). Physicians completed an online questionnaire that explored their current habits and the determinants for prescribing antibiotics and probiotics. For the 731 physicians who completed the questionnaire (390 paediatricians and 341 GPs), 37% of all consultations for a child led to the prescription of antibiotics (ranging from 17% in Australia to 47% in India). A large majority of physicians (84%) agreed that antibiotics disrupted gut microbiota and considered probiotics an effective intervention to prevent AAD (68%). However, only 33% co-prescribed probiotics with antibiotics (ranging from 13% in Japan to 60% in South Korea). The main reasons for prescribing probiotics were previous episodes of AAD (61%), presence of diarrhoea (55%), prolonged antibiotic treatment (54%) or amoxicillin-clavulanic acid therapy (54%). Although current local guidelines recommend the use of selected probiotics in children receiving antibiotics in Asia-Pacific area, the rates of antibiotics and probiotics prescription significantly vary among countries and are deeply affected by country-related cultural and organisational issues.

Recommendations for probiotics are available in several regions. This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomized controlled trials in the region were revised. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by applying the Likert scale and rated using the GRADE system. Saccharomyces boulardii CNCM I-745 (Sb) and Lactobacillus rhamnosus GG ( LGG ) were strongly recommended as adjunct treatment to oral rehydration therapy for gastroenteritis. Lactobacillus reuteri could also be considered. Probiotics may be considered for prevention of (with the indicated strains): antibiotic-associated diarrhea (LGG or Sb); Clostridium difficile -induced diarrhea (Sb); nosocomial diarrhea (LGG); infantile colic ( L reuteri ) and as adjunct treatment of Helicobacter pylori (Sb and others). Specific probiotics with a history of safe use in preterm and term infants may be considered in infants for prevention of necrotizing enterocolitis. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations apply well to Asia pacific countries. These need to be validated with local randomized-controlled trials., Competing Interests: Conflict-of-interest statement: The working group meeting was funded by a medical education grant from Biocodex, France. Professor Yamashiro has received research funding from Yakult Honsha Co. Ltd. Japan. All other authors have no conflicts of interest to declare.

Gut bacterial translocation to the blood may play an important role in the development of insulin resistance in type 2 diabetes. Here, we performed an interventional randomised control study to investigate whether probiotics could reduce bacterial translocation and cause changes in the gut microbiota. Seventy Japanese patients with type 2 diabetes were randomised to two groups: the probiotic group drank Lactobacillus casei strain Shirota-fermented milk, while the control group ingested no probiotics. The trial was conducted for 16 weeks. At baseline, 8 and 16 weeks, the gut microbiota composition in feces and blood, fecal organic acids, and other biochemical parameters were measured. At the end of the study, the fecal counts of the Clostridium coccoides group and Clostridium leptum subgroup in the probiotic group were significantly higher than in the control group. As expected, the fecal counts of total Lactobacillus were significantly higher in the probiotic group. Intriguingly, the total count of blood bacteria was significantly lower in the probiotic group. However, fecal organic acids were comparable between the two groups. Our results showed that probiotic administration reduced bacterial translocation and altered the gut microbiota in Japanese patients with type 2 diabetes mellitus.

There are few data regarding the role of probiotics as a dietary intervention in the management of obesity in children. An open prospective examination was conducted to clarify the effects of Lactobacillus casei strain Shirota (LcS)-containing beverages in obese children. We compared the intestinal microbiota and organic acid levels between 12 obese (average age, 10.8 years; body mass index (BMI) Z score, 2.7±1.7) and 22 control children(average age, 8.5 years; BMI Z score, 0.1±0.7), and pre- and post-intervention in the obese children. The obese group underwent diet and exercise therapy for 6 months and then were given an LcS beverage daily for another 6 months and the body weight and serological markers were monitored. Significant reductions in the faecal concentrations of Bifidobacterium (obese group, 7.9±1.5 vs non-obese group, 9.8±0.5 Log 10 cells/g; P<0.01) along with a significant decline in the Bacteroides fragilis group, Atopobium cluster and Lactobacillus gasseri subgroup, and acetic acid (obese group, 45.1±16.9 vs non-obese group, 57.9±17.6 μmol/g; P<0.05) were observed in the obese group at baseline. A significant decline in body weight (-2.9±4.6%; P<0.05) and an elevation in the high density lipoprotein cholesterol level (+11.1±17.6%; P<0.05) were observed 6 months after ingestion of the LcS beverage compared to baseline. Furthermore, a significant increase in the faecal concentration of Bifidobacterium (7.0±1.2 before ingestion vs 9.1±1.2 Log 10 cells/g after ingestion; P<0.01) and an apparent increase in the acetic acid concentration (7.0±1.2 before ingestion vs 9.1±1.2 Log 10 cells/g after ingestion; P<0.01) were observed 6 months after ingestion. LcS contributed to weight loss while also improving the lipid metabolism in obese children via a significant increase in the faecal Bifidobacterium numbers and the acetic acid concentration.

Major surgical procedures can alter intestinal microbiota and disrupt the intestinal barrier function, leaving the patient at risk for infection. Probiotics are defined as live microorganisms that confer a health benefit on the host when administered in adequate amounts. Although the efficacy of administering probiotics perioperatively to adults has been reported, the clinical significance of probiotics in children undergoing surgery is still unclear. This study provides a brief overview of our randomized controlled trial of preoperative probiotic administration to children, and discusses the relationship between probiotics and their effects in the perioperative period, particularly focusing on bacteremia., (© 2017 S. Karger AG, Basel.)

The efficacy of perioperative probiotic administration has been reported in adults. We examined the effects of orally administered Bifidobacterium breve strain Yakult (BBG-01) on outcomes in pediatric surgical cases by assessing intestinal and blood microbiota. BBG-01 was well tolerated without adverse effects, and postoperative infectious complications were significantly decreased. Fecal analysis showed increased Bifidobacterium and decreased Enterobacteriaceae, Clostridium difficile, and Pseudomonas. Concentrations of fecal acetic acid were significantly increased, maintaining fecal pH at <7.0. The incidence of detecting bacteria in blood was significantly reduced. BBG-01 improved the intestinal environment, and may be implicated in suppressing bacterial translocation.

Backgrounds/aims: To clarify the usefulness of Lactobacillus casei strain Shirota (LcS)-fermented milk in the normalization of bowel movements and improvement of infection control for the elderly residents and staff of facilities for the elderly., Methods: A randomized placebo-controlled double-blind test was performed among the elderly residents (average age, 85) and staff members (average age, 37) of facilities for the elderly. The participants randomly received either LcS-fermented milk or a placebo beverage once daily for 6 months. Clinical data and enteric conditions were compared between the 2 groups., Results: A significantly lower incidence of fever and improved bowel movements were seen in the LcS-fermented milk group (n = 36) in comparison to the placebo group (n = 36). The numbers of Bifidobacterium and Lactobacillus were significantly higher (p < 0.01), the numbers of destructive bacteria such as Clostridium difficile were significantly lower (p < 0.05), and the fecal acetic acid concentration and total acidity were significantly higher in the LcS group. A significant difference in the intestinal microbiota, fecal acetic acid, and pH was also observed between the LcS and placebo groups among the facility's staff members., Conclusions: The long-term consumption of LcS-fermented milk may be useful for decreasing the daily risk of infection and improving the quality of life among the residents and staff of facilities for the elderly., (© 2015 S. Karger AG, Basel.)

Objectives: This study aims to establish the baseline profile of intestinal microbiota in pre-school and school-age Japanese children and to investigate the effects of a probiotic on the microbiota., Methods: We analyzed the intestinal microbiota and investigated the effects (before, during and after the ingestion period) on intestinal microbiota and the environment of 6 months of daily ingestion of a probiotic (Lactobacillus casei strain Shirota (LcS)-fermented milk)., Results: We performed an open trial in 23 children (14 boys, 9 girls; age 7.7 ± 2.4 years (mean ± SD); BMI 19.6 ± 4.6). The composition of intestinal microbiota of healthy pre-school and school-age children resembled that of adults. During probiotic supplementation, the population levels of Bifidobacterium and total Lactobacillus increased significantly, while those of Enterobacteriaceae, Staphylococcus and Clostridium perfringens decreased significantly. A significant increase in fecal concentrations of organic acids and also a decrease in fecal pH were observed during the ingestion period. However, the patterns of fecal microbiota and intestinal environment were found to revert to the baseline levels (i.e. before ingestion) within 6 months following the cessation of probiotic intake., Conclusion: Regular intake of an LcS-containing probiotic product may modify the gut microbiota composition and intestinal environment in pre-school and school-age children while maintaining the homeostasis of the microbiota., (© 2015 S. Karger AG, Basel.)

Unlabelled: Interaction of probiotic bacteria with the host immune system elicits beneficial immune modulating effects. Although, there are many published studies on interaction of probiotics with immune system focusing on activation of immune system by bacterial cell wall through the engagement of Toll-like receptor family; very few studies have focused on molecules involved in the T-cell activation, and not much work has been executed to study the correlation of probiotics and programmed death-1 in colorectal carcinogenesis in animal models. Hence, the present study was carried out to assess the effect of probiotic Dahi on expression of programmed death (PD-1) in colorectum of 1, 2-dimethylhydrazine treated Wistar rats., Methods: DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 168 male Wistar rats were randomly allocated to seven groups, each group having twenty-four animals. The rats were euthanized at the 8th, 16th and 32nd week of the experiment and examined for the expression of PD-1 in colorectal tissues by immunohistochemical staining., Results: Expression of PD-1 was observed in colorectal tissues of normal and DMH-treated rats. Feeding rats with probiotic Dahi or the treatment with piroxicam decreased the expression of PD-1 in DMH-induced colorectal mucosa, and the combined treatment with probiotic Dahi and piroxicam was significantly more effective in reducing the expression of PD-1., Conclusion: PD-1 expressed independent of carcinogen administration in normal colonic mucosa and may play a role in modulation of immune response in DMH-induced colorectal carcinogenesis. The present study suggests that probiotic Dahi can be used as an effective chemopreventive agent in the management of colorectal cancer.

For conducting effective risk management in long-stay elderly people at a health service facility, we performed an open case-controlled study to evaluate the effect of the intake of probiotic-fermented milk containing Lactobacillus casei strain Shirota (LcS-fermented milk) on norovirus gastroenteritis occurring in the winter season during the intake period. A total of seventy-seven elderly people (mean age 84 years) were enrolled in the study. During a 1-month period, there was no significant difference in the incidence of norovirus gastroenteritis between the LcS-fermented milk-administered (n 39) and the non-administered (n 38) groups; however, the mean duration of fever of >37°C after the onset of gastroenteritis was 1·5 (SD 1·7) d in the former and 2·9 (SD 2·3) d in the latter group, showing a significant shortening in the former group (P < 0·05). RT-quantitative PCR analysis targeting ribosomal RNA showed both Bifidobacterium and Lactobacillus to be significantly dominant, whereas Enterobacteriaceae decreased in faecal samples from the administered group (n 10, mean age 83 years), with a significant increase in faecal acetic acid concentration. Continuous intake of LcS-fermented milk could positively contribute to the alleviation of fever caused by norovirus gastroenteritis by correcting the imbalance of the intestinal microflora peculiar to the elderly, although such consumption could not protect them from the disease.

This review reports the beneficial effects, observed in our clinical studies, of Bifidobacterium breve for premature infants, and children with cancers undergoing chemotherapy. To investigate the protective effects of B. breve (M-16V) as a probiotic on necrotizing enterocolitis (NEC) and infection in premature infants, we carried out a clinical study in 338 very low birth weight infants over a five-year period. These patients were supplemented with B. breve starting several hours after birth (Bifido group). 226 premature infants served as controls. Infants of the Bifido group were administered B. breve in a daily dose of 1×10(9) cells/day. The incidence of NEC was significantly reduced in the Bifido group (nil) compared with that in controls (6 cases, P<0.01). Infection also decreased significantly. Thus, administration of B. breve as a probiotic looks to be a very effective treatment for preventing NEC and infection in preterm infants. Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of chemotherapy treatment. To evaluate the effects of the administration of B. breve (BBG-01, another strain than that used in the study of premature infants), a clinical study was performed to ascertain whether it attenuated intestinal mucositis in children with cancers on chemotherapy. A placebo-controlled trial was performed in patients with malignancies admitted for chemotherapy (n=42), who were randomised into two groups receiving probiotic or placebo. The frequency of fever and the use of intravenous antibiotics were significantly lower in the Bifido group than the placebo group. The B. breve administration enhanced the colonisation of anaerobes. Disruption of the intestinal microbiota after chemotherapy, such as the increase in the population levels of Enterobacteriaceae, was more pronounced in the placebo group. In conclusion, these data suggest that administration of B. breve is an effective approach to attenuating chemotherapy-induced mucositis in children with cancers. The study results strongly suggest that B. breve administration as a probiotic is an effective therapy for the prevention of NEC and infection in premature infants, and also a promising treatment for attenuating chemotherapy-induced mucositis in children with cancers.

Summary: In order to clarify the probiotic features of immunomodulation, cytokine production by murine spleen and Peyer's patch (PP) cells was examined in response to probiotic and pathogenic bacteria. In spleen cells, probiotic Lactobacillus casei induced interleukin (IL)-12 production by CD11b(+) cells more strongly than pathogenic Gram-positive and Gram-negative bacteria and effectively promoted the development of T helper (Th) type 1 cells followed by high levels of secretion of interferon (IFN)-gamma. Although the levels of IL-12 secreted by PP cells in response to L. casei were lower in comparison with spleen cells, Th1 cells developed as a result of this low-level induction of IL-12. However, IFN-gamma secretion by the L. casei-induced Th1 cells stimulated with a specific antigen was down-regulated in PP cells. Development of IL-17-producing Th17 cells was efficiently induced in PP cells by antigen stimulation. Lactobacillus casei slightly, but significantly, inhibited the antigen-induced secretion of IL-17 without a decrease in the proportion of Th17 cells. No bacteria tested induced the development of IL-10-producing, transforming growth factor-beta-producing or Foxp3-expressing regulatory T cells, thus suggesting that certain probiotics might regulate proinflammatory responses through as yet unidentified mechanisms in PP cells. These data show probiotic L. casei to have considerable potential to induce IL-12 production and promote Th1 cell development, but the secretion of proinflammatory cytokines such as IL-12 and IL-17 may be well controlled in PP cells.

Purpose: Probiotics are expected to be effective in prophylaxis of infection in cancer patient, since infections in neutropenics are mainly caused by endogenous flora through the intestinal mucosa. However, the experience with the use of probiotics in immunocompromised patients is limited, and precise fecal bacteria analysis has not been reported. The aim of the study was to evaluate the effects of the enteral administration of the probiotic, Bifidobacterium breve strain Yakult, on its ability to prevent infection, fecal micro flora, and intestinal environments in cancer patients on chemotherapy., Methods: A placebo-controlled trial was performed at Juntendo University Hospital. Patients with malignancies admitted for chemotherapy (n = 42) were randomized into two groups receiving probiotic or placebo. The effects on infectious complications, natural killer cells, fecal micro flora, fecal organic acid concentrations, and fecal pH were studied., Results: The frequency of fever and the use of intravenous antibiotics were lower in the probiotic group than the placebo group. The probiotic administration enhanced the habitation of anaerobes. Disruption of the intestinal microbiota after chemotherapy such as the increase in the population levels of Enterobacteriaceae was observed at more pronounced manner in the placebo group in comparison to the probiotic group. The concentrations of total organic acids were maintained most of the time at the normal level, which constantly maintained the pH below 7.0 only in the probiotic group., Conclusion: These data, although based on a limited number of patients and samples, suggest that administration of B. breve strain Yakult could be an effective approach for achieving clinical benefits in immunocompromised hosts by improving their intestinal environments.

As part of medical risk management in a long-term stay facility for the elderly, we introduced probiotic fermented milk containing Lactobacillus casei strain Shirota (LcS-fermented milk) in an open case-control study of its effect of (1 bottle a day) on winter-time norovirus gastroenteritis. During the 1 month from December 1 to 31, 2006, norovirus gastroenteritis occurred in 21 (55%) of 38 cases in the nonmilk group, and in 27 (64%) of 39 cases in the milk group, showing no statistically significant difference. The mean duration of >37 degrees C fever after disease onset, however, was 2.9+/-2.3 days in the non-milk group and 1.5+/-1.7 days in the milk group, showing significant shortening (p<0.05). The duration of > 38 degrees C fever after disease onset also tended to be shorter. No significant differences were seen in age, gender, days of antipyretic use, or stool-free days. These results suggested that continuous intake of LcS-fermented milk could aggravate fever duration in elderly long-term rest home residents although it probably did not prevent noroviral gastroenteritis onset.

Objectives: Transforming growth factor (TGF) beta1 displays a broad spectrum of activities in mucosal regulation, including induction of oral tolerance, potent anti-inflammatory effects, mucosal IgA expression and effects on epithelial cell proliferation and differentiation. The present study examined the effect of probiotics on the immunologic system of preterm infants in relation to TGF-beta signaling., Methods: Subjects comprised 19 preterm infants divided into 2 groups: receiving Bifidobacterium breve supplementation (B. breve group) and without supplementation (controls). Blood samples were collected from both groups on days 0, 14 and 28 after birth. Serum cytokine levels were measured using enzyme-linked immunosorbent assay, and expression levels of the TGF-beta signaling molecule, Smad, were examined using semiquantitative reverse transcriptase-polymerase chain reaction., Results: Serum TGF-beta1 level was elevated on day 14 and remained elevated on day 28 in the B. breve group. Level of messenger RNA expression was enhanced for Smad3 and reduced for Smad7 (antagonistic Smad) after B. breve administration relative to levels in controls on day 28., Conclusions: These results demonstrated that the administration of B. breve to preterm infants can up-regulate TGF-beta1 signaling and may possibly be beneficial in attenuating inflammatory and allergic reactions in these infants.