title: Multicentric study of the effect of milk fermented by Lactobacillus casei on the incidence of diarrhoea. Enhancement of the Circulating Antibody Secreting Cell Response in Human Diarrhea by a Human Lactobacillus Strain A trial in the Karelian Republic of oral rehydration and Lactobacillus GG for treatment of acute diarrhoea Lactic Acid Bacteria in the Treatment of Acute Rotavirus Gastroenteritis Oral bacterial therapy reduces the duration of symptoms and of viral excretion in children with mild diarrhea. Lactobacillus GG and acute diarrhoea in young children in the tropics. Management of acute diarrhoea with low osmolarity oral rehydration solutions and Lactobacillusstrain GG Clinical evaluation of the addition of lyophilized, heat-killed Lactobacillus acidophilus LB to oral rehydration therapy in the treatment of acute diarrhea in children. Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial. A placebo-controlled trial of Lactobacillus GG to prevent diarrhea in undernourished Peruvian children. The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114 001) on acute diarrhoea in children attending day care centres. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children. Lactobacillus GG promotes recovery from acute nonbloody diarrhea in Pakistan. Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus
abstract: The aim of this study was to determine if supplementation of healthy children with milk fermented by yogurt cultures and Lactobacillus casei strain DN-114 001 could affect the incidence of acute diarrhoea when compared with traditional yogurt . The study was a multicentre , r and omised , double-blind trial , conducted over four months , on 928 children aged , at inclusion , 6 - 24 months . The study consisted of two periods : supplementation and observation . Subjects were supplemented daily with 100 g of one of the two dairy products being tested : st and ard yogurt and milk fermented by yogurt cultures and Lactobacillus casei ( 10(8 ) cfu/ml ) . Frequency or duration of any diarrhoea episode was evaluated . As far as frequency was concerned there was a statistically significant difference between the groups , the incidence of diarrhoea being significantly reduced by supplementation with L. casei fermented milk ( 15.9 % ) compared with yogurt ( 22 % ) ( p = 0.03 ) . These results suggest an additional benefit of L. casei in acute diarrhoea in children compared with st and ard yogurt ABSTRACT : Human Lactobacillus sp strain GG ( Lactobacillus GG ) administered during acute rotavirus diarrhea has been shown to promote clinical recovery . To eluci date the immune mechanisms behind such a favorable outcome , the ELISPOT ( solid phase enzyme-linked immunospot ) assay of Ig- and specific antibody-secreting cells among circulating lymphocytes was used , giving indirect evidence of the immunologic events in the gut . After rehydration , 39 children with acute rotavirus diarrhea , mean age 16 ( SD 6 ) mo , r and omly received either a Lactobacillus GG fermented milk product ( study group ) or a pasteurized yogurt ( placebo group ) . The duration of diarrhea was significantly shorter in the study group than in the placebo group [ mean 1.1 ( SD 0.6 ) versus 2.5 ( SD 1.4 ) d , p = 0.001 ] . Lactobacillus GG therapy was associated with a significantly enhanced nonspecific humoral response during the acute phase of the infection , reflected in the IgG , IgA , and IgM Ig-secreting cell numbers . At convalescence , 90 % of the study group versus 46 % of the placebo group had developed an IgA specific antibody-secreting cell response to rotavirus ( p = 0.006 ) . The results indicate that Lactobacillus GG promotes recovery from rotavirus diarrhea via augmentation of the local immune defense . Furthermore , specific IgA response to rotavirus is endorsed , which is possibly relevant in protection against reinfections In a controlled trial in Petrozavodsk , Karelia , the effects of oral rehydration and Lactobacillus strain GG ( LGG ) on  recovery  from  acute diarrhoea ( 27 % rotavirus , 21 % bacterial aetiology ) were studied in 123 children aged between 1 and 36 months of age . On admission to hospital , the patients were first r and omized to receive either isotonic oral rehydration solution ( ORS ) with osmolality 311mosmol/l and sodium 90mmol/l ( WHO‐ORS ) , or a hypotonic ORS with osmolality 224mosmol/l and sodium 60mmol/l ( Light‐ORS ) , and thereafter r and omized to receive either 5 × 109 colony forming units of LGG or a matching placebo . The two ORS performed equally for acute rehydration , and oral rehydration with either ORS was associated with a shorter duration of diarrhoea than intravenous rehydration ( p= 0.036 ) . Patients receiving LGG had a significantly shorter duration of watery diarrhoea [ mean ( SD ) 2.7 ( 2.2 ) days ] than those receiving the placebo [ 3.7 ( 2.8 ) days , p= 0.03 ] . LGG significantly shortened the duration of rotavirus diarrhoea but not diarrhoea with confirmed bacterial aetiology We compared different lactic acid bacteria for their effect on the immune response to rotavirus in children with acute rotavirus gastroenteritis . After initial oral rehydration , 49 children aged 6 to 35 months with rotavirus gastroenteritis r and omly received cither Lactobacillus casei subsp . casei strain GG ( LGG ) , L. casei subsp . rhamnosus ( Lactophilus ) , or a combination of Streptococcus thermophilus and L. delbriickii subsp . bulgaricus ( Yalacta ) twice daily for 5 days . Serum antibodies to rotavirus , total number of immunoglobulin-sec rct ing cells ( ISC ) , and specific antibody-secreting cells ( sASC ) to rotavirus were measured at the acute stage and at convalescence . The mean ( SD ) duration of diarrhea was 1.8 ( 0.8 ) days in children who received LGG , 2.8 ( 1.2 ) days in those receiving Lactophilus , and 2.6 ( 1.4 ) days in those receiving Yalacta ( F = 3.3 , p = 0.04 ) . The ISC response was comparable in the three study groups , but the rotavirus-specific immune responses were different . LGG therapy was associated with an enhancement of IgA sASC to rotavirus and serum IgA antibody level at convalescent stage . We conclude that certain strains of lactic acid bacteria , particularly LGG , promote serum and intestinal immune responses to rotavirus , and thus may be important in establishing immunity against rotavirus BACKGROUND Oral administration of live Lactobacillus casei strain GG is associated with the reduction of duration of diarrhea in children admitted to the hospital because of diarrhea . The purpose s of this work were to investigate the clinical efficacy of oral administration of Lactobacillus in children with mild diarrhea who were observed as out patients , and to see whether Lactobacillus GG can reduce the duration of rotavirus excretion . METHODS Duration of diarrhea was recorded in 100 children seen by family pediatricians and r and omly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized Lactobacillus casei , strain GG .  Rotavirus was looked for in the stools of all children and in those in whom results were positive , stools were examined again 6 days after the onset of diarrhea . RESULTS In 61 children results were positive for rotavirus and in 39 results were negative . Duration of diarrhea was reduced from 6 to 3 days in children receiving Lactobacillus GG , with a similar pattern in rotavirus-positive and -negative children . Six days after the onset of diarrhea , stools in only 4 out of 31 children that received Lactobacillus GG were positive for rotavirus compared with positive findings in 25 out of 30 control subjects . CONCLUSIONS Oral administration of Lactobacillus GG is effective in rotavirus-positive and rotavirus-negative ambulatory children with diarrhea . Furthermore , it reduces the duration of rotavirus excretion A prospect i ve , placebo controlled , triple blind clinical trial was undertaken in Thail and to determine the effect of Lactobacillus GG on recovery from acute diarrhoea in children . Thirty-nine children ( mean age = 8 months ) were enrolled and following rehydration received either oral Lactobacillus GG ( n = 20 ) as a freeze-dried preparation or placebo ( n = 19 ) twice daily for 2 days . The clinical characteristics of the study groups were similar . There was no significant difference overall in clinical response detected between the study groups . When only those with acute non-bloody diarrhoea ( n = 26 ) were considered , the mean duration of diarrhoea was significantly shorter in the lactobacillus group ( 1.9 days ) than in the placebo group ( 3.3 days ) ( P < 0.055 ) . Stool frequency was less on the second day in the lactobacillus group ( P < 0.05 ) . The results suggest that Lactobacillus GG accelerates  recovery  from acute watery diarrhoea in young children in a tropical setting Two hypotonic oral rehydration solutions with osmolarities of 224 mosmol/l ( Na+ 60 mmol/l , glucose 84 mmol/l ) and 204 mosmol/l ( Na+ 60 mmol/l , glucose 64 mmol/l ) , respectively , and oral treatment withLactobacillus GG were evaluated in a double blind trial in children aged 6–36 months hospitalised for acute diarrhoea . Early administration ofLactobacillus GG at the start of oral rehydration result ed in the shortest duration of diarrhoea , best weight gain , and fastest correction of acidosis . A reduced osmolarity oral rehydration solution  ( 224 mosmol/l ) combined with early administration of Lactobacillus GG is an effective treatment for acute diarrhoea  in young children ; further reduction of osmolarity may not be beneficial BACKGROUND Addition of a medication to the World Health Organization protocol for treatment of acute diarrhea in children is controversial . In this trial , the clinical efficacy of a medication ( Lactéol Fort sachets ; Laboratoire du Lactéol du Docteur Boucard , Houdan France ) containing lyophilized heat-killed Lactobacillus acidophilus LB was assessed as an adjunct to oral rehydration therapy . METHODS Children aged 3 to 24 months with acute diarrhea and mild or moderate dehydration were enrolled in the study . Children received oral rehydration therapy for the first 4 hours . After this first rehydration phase , undiluted milk formula or breast milk was fed alternately with oral rehydration solution . Children were fed rice gruel as tolerated . They received either one sachet containing 10 billion of lyophilized heat-killed L. acidophilus LB or placebo at admission and at 12-hour intervals for five doses . RESULTS Seventy-three children ( 37 L. acidophilus LB , 36 placebo ) were enrolled , of whom 40 ( 17 L. acidophilus LB , 23 placebo ) received an antibiotic before inclusion . Rotavirus was identified in approximately 50 % of the children in each group . After 24 hours of treatment , the number of rotavirus-positive children with watery stools was significantly lower ( p = 0.012 ) in the L. acidophilus LB group . Mean duration of diarrhea was decreased ( p = 0.034 ) with L. acidophilus LB ( 43.4 hours ) versus placebo ( 57.0 hours ) . This decreased duration was particularly marked in children with no antibiotic therapy before inclusion ( 31.1 hours ) : 42.9 hours for the L. acidophilus LB group versus 74.0 hours for the placebo group ( p = 0.016 ) . CONCLUSIONS Addition of L. acidophilus LB to oral rehydration therapy was effective in the treatment of children with acute diarrhea by decreasing the duration of diarrhea BACKGROUND Certain lactic acid bacteria may accelerate recovery from acute diarrhea .  Lactobacillus reuteri is a commonly occurring Lactobacillus species with therapeutic potential in diarrhea . DESIGN Prospect i ve , r and omized , placebo-controlled trial in two hospitals . METHODS Children between 6 and 36 months of age admitted for rotavirus-associated diarrhea were r and omized into three groups to receive either 10(10 ) or 10(7 ) colony-forming units ( cfu ) of L. reuteri or a matching placebo once a day for up to 5 days . RESULTS The main effect of L. reuteri was on the duration of watery diarrhea . The mean ( + /-SD ) duration of watery diarrhea after initiation of treatment was 2.5 ( 1.5 ) days in the placebo group ( n = 25 ) vs. 1.9 ( 0.9 ) days in the small dosage ( n = 20 ) and 1.5 ( 1.1 ) days in the large dosage ( n = 21 ) L. reuteri recipients ( P = 0.01 ) . By the second day of treatment watery diarrhea persisted in 80 % of the placebo , 70 % of the small dosage and 48 % of the large dosage L. reuteri recipients ( P = 0.04 , large dosage vs. placebo ) . Stool cultures for lactobacilli confirmed that administration of L. reuteri result ed in good colonization of the GI tract . The mean ( + /-SD ) of total Lactobacillus count 2 days after treatment initiation was 2.8 ( 1.6 ) log 10 cfu/g in the placebo group , 4.5 ( 2.0 ) log 10 cfu/g in the small dosage L. reuteri group and 6.1 ( 1.2 ) log 10 cfu/g in the large dosage L. reuteri group ( P = 0.0004 ) . CONCLUSIONS L. reuteri effectively colonized the gastrointestinal tract after administration and significantly shortened the duration of watery diarrhea associated with rotavirus . There was a correlation between the dosage of L. reuteri and the clinical effect BACKGROUND The probiotic Lactobacillus GG is effective in promoting a more rapid recovery of acute , watery diarrhea in children with rotavirus enteritis . Very limited information is available , however , on the potential role of such agents in non-rotaviral diarrheal episodes . Furthermore , no evidence is available concerning the efficacy of Lactobacillus GG administered in the oral rehydration solution during oral rehydration therapy . A multicenter trial was conducted to evaluate the efficacy of Lactobacillus GG administered in the oral rehydration solution to patients with acute-onset diarrhea of all causes . METHODS Children 1 month to 3 years of age with acute-onset diarrhea were enrolled in a double-blind , placebo-controlled investigation . Patients were r and omly allocated to group A , receiving oral rehydration solution plus placebo , or group B , receiving the same preparation but with a live preparation of Lactobacillus GG ( at least 10(10 ) CFU/250 ml ) . After rehydration in the first 4 to 6 hours , patients were offered their usual feedings plus free access to the same solution until diarrhea stopped . RESULTS One hundred forty children were enrolled in group A , and 147 in group B. There were no differences at admission between the groups in age , sex , previous types of feeding , previous duration of diarrhea , use of antibiotics , weight , height , weight-height percentile , prevalence of fever , overall status , degree of dehydration , and percentage of in- versus out patients . Duration of diarrhea after enrollment was 71.9 + /- 35.8 hours in group A versus 58.3 + /- 27.6 hours in group B ( mean + /- SD ; P = 0.03 ) . In rotavirus-positive children , diarrhea lasted 76.6 + /- 41.6 hours in group A versus 56.2 + /- 16.9 hours in groups B ( P < 0.008 ) . Diarrhea lasted longer than 7 days in 10.7 % of group A versus 2.7 % of group B patients ( P < 0.01 ) . Hospital stays were significantly shorter in group B than in group A. CONCLUSIONS Administering oral rehydration solution containing Lactobacillus GG to children with acute diarrhea is safe and results in shorter duration of diarrhea , less chance of a protracted course , and faster discharge from the hospital OBJECTIVE Lactobacillus GG ( L-GG ) , an acid- and bile-resistant strain that colonizes the intestinal mucosa , has been used to manage diarrhea in children . Our objective was to evaluate the prophylactic use of L-GG to prevent diarrhea in children at high risk from a developing country in a r and omized , placebo-controlled trial . STUDY DESIGN Two hundred four undernourished children 6 to 24 months old from an indigent peri-urban Peruvian town received either L-GG or placebo in flavored gelatin once daily , 6 days a week , for 15 months . Episodes of diarrhea were documented by daily home visits , and diagnostic studies were done in a subset of cases . Recovery of L-GG in stool from subjects and from family contacts was examined . RESULTS Subjects in the L-GG group had significantly fewer episodes of diarrhea ( 5.21 episodes diarrhea/child/year [ ' ecy ' ] L-GG group , 6 . 02 ecy placebo group ; P = .028 ) . The decreased incidence of diarrhea in the L-GG group was greatest in the 18- to 29-month age group ( P = . 004 ) and was largely limited to nonbreastfed children ( Breastfed : 6 . 59 ecy L-GG , 6.32 ecy placebo , P = .7 ; Nonbreastfed : 4.69 ecy L-GG , 5 . 86 ecy placebo , P = .005 ) . The duration of diarrhea episodes and the causes of diarrhea were similar in both groups , except adenovirus was more common in the placebo group . CONCLUSION L-GG supplementation may be useful as a prophylactic measure to control diarrhea in undernourished children at increased risk , especially nonbreastfed children in the toddler age group The objective of this study was to determine if supplementation with milk fermented by yogurt cultures and Lactobacillus casei ( strain DN-114 001 ) could lessen  acute diarrhoea in healthy children . The study was conducted over six months , with 287 children aged 18.9 ( SD 6.0 ) months , comprising three periods of one month supplementation , each month being followed by one month without supplementation . Subjects were supplemented daily with either 125 g or 250 g ( according to age ) of one of three tested dairy products : st and ard yogurt , milk fermented by yogurt cultures and Lactobacillus casei ( 10(8 ) cfu/ml ) , or a jellied milk ( control product ) . A daily record was kept of the number and type of stools . Although the incidence of diarrhoea was not shown to be different between the groups , the severity of diarrhoea over the six-month study was significantly decreased ( 4.3 days ) with the supplementation of L. casei fermented milk compared with the jellied milk ( 8.0 days ) ( p = 0.009 ) To determine the effect of a human Lactobacillus strain  ( Lactobacillus casei sp strain GG , Gefilac ) on  recovery from acute diarrhea ( 82 % rotavirus ) , 71 well-nourished children between 4 and 45 months of age were studied . After oral rehydration , the patients r and omly received either Lactobacillus GG-fermented milk product , 125 g ( 10(10 - 11 ) colony-forming units ) twice daily ( group 1 ) ; Lactobacillus GG freeze-dried powder , one dose ( 10(10 - 11 ) colony-forming units ) twice daily ( group 2 ) ; or a placebo , a pasteurized yogurt ( group 3 ) 125 g twice daily ; each diet was given for 5 days , in addition to normal full diet otherwise free of fermented dairy products . The mean ( SD ) duration of diarrhea after commencing the therapy was significantly shorter in group 1 ( 1.4 [ 0.8 ] days ) and in group 2 ( 1.4 [ 0.8 ] days ) than in group 3 ( 2.4 [ 1.1 ] days ) ; F = 8.70 , P less than 0.001 . After rehydration , each dietary group maintained a positive weight trend . The urinary lactulose-mannitol recovery ratios ( means [ 95 % confidence intervals ] ) on admission were 0.09 ( 0.03 , 0.24 ) in group 1 , 0.12 ( 0.07 , 0.22 ) in group 2 , and 0.08 ( 0.04 , 0.18 ) in group 3 ; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation . The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea . It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea BACKGROUND Certain strains of lactobacilli may promote recovery from acute diarrhea . Lactobacillus reuteri is of human origin and is a natural colonizer of gastrointestinal tract . In this trial , exogenously administered L. reuteri was studied as a therapeutic agent in acute diarrhea . METHODS Forty patients between 6 and 36 months of age hospitalized with acute diarrhea ( 75 % rotavirus ) were studied . After parental consent , the patients were r and omized to one of two treatment groups to receive either 10(10 ) to 10(11 ) colony-forming units of L. reuteri or a matching placebo daily for the length of hospitalization or up to 5 days . The clinical outcome of diarrhea and colonization of L. reuteri were evaluated . RESULTS The mean ( SD ) duration of watery diarrhea after treatment was 1.7 ( 1.6 ) days in the L. reuteri group and 2.9 ( 2.3 ) days in the placebo group ( p = 0.07 ) . On the second day of treatment only 26 % of patients receiving L. reuteri had watery diarrhea , compared with 81 % of those receiving placebo ( p = 0.0005 ) . Cultures of lactobacilli from stool sample s demonstrated that administration of L. reuteri result ed in colonization of the gastrointestinal tract . Lactobacillus reuteri accounted for > 75 % of the total lactobacilli found in children fed with this product . CONCLUSIONS Lactobacillus reuteri is effective as a therapeutic agent in acute rotavirus diarrhea in children . Further studies are warranted to confirm the present finding and to explore the full therapeutic potential of L. reuteri in acute viral diarrhea A prospect i ve , placebo-controlled , triple blind clinical trial was carried out in Pakistan to determine the effect of Lactobacillus GG on the course of  acute diarrhea in hospitalized children . Forty children ( mean age , 13 months ) were enrolled and after rehydration received either oral Lactobacillus GG ( n = 21 ) or placebo ( n = 19 ) twice daily for 2 days , in addition to the usual diet . The clinical course of diarrhea was followed during the treatment period . Features on admission into the study groups were similar and were characterized by severe diarrhea , malnutrition and inappropriate management before presentation . Response was evident on Day 2 when the frequency of both vomiting and diarrhea was less in the Lactobacillus group . In those who had presented with acute nonbloody diarrhea ( n = 32 ) , the percentage of children with persistent watery diarrhea at 48 hours was significantly less in the Lactobacillus group : 31 % vs. 75 % ( P < 0.01 ) . No significant difference was observed by 48 hours in those presenting with bloody diarrhea . The relevance of this finding to the management of diarrhea in the tropics is discussed Acute diarrhoea is a serious cause of infant morbidity and mortality , and the development of preventive measures remains an important goal . Bifidobacteria ( which constitute the predominant intestinal flora of breastfed infants ) , as well as other lactic-acid-producing organisms such as Streptococcus thermophilus , are thought to have a protective effect against acute diarrhoeal disease . However , their efficacy has not been assessed in controlled trials . In a double-blind , placebo-controlled trial , infants aged 5 - 24 months who were admitted to a chronic medical care hospital were r and omised to receive a st and ard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus . Patients were evaluated daily for occurrence of diarrhoea , and faecal sample s , obtained weekly , were analysed for rotavirus antigen by enzyme immunoassay . Faecal sample s were also obtained during an episode of diarrhoea for virological and bacteriological analyses . 55 subjects were evaluated for a total of 4447 patient-days during 17 months . 8 ( 31 % ) of the 26 patients who received the control formula and 2 ( 7 % ) of 29 who received the supplemented formula developed diarrhoea during the course of the study ( p = 0.035 , Fisher 's exact test , two-tailed ) . 10 ( 39 % ) of the subjects who received the control formula and 3 ( 10 % ) of those who received the supplemented formula  shed rotavirus at some time during the study ( p = 0.025 ) . The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital
target: Only Lactobacillus GG showed a consistent effect .
  There is evidence of a clinical ly significant benefit of probiotics in the treatment of  acute infectious diarrhea in infants and children , particularly in rotaviral gastroenteritis .
  Lactobacillus GG showed the most consistent effect , although other probiotic strains may also be effective .
  Clinical and statistical heterogeneity of the prophylactic interventions preclude drawing firm conclusions about the efficacy of probiotics in preventing acute gastroenteritis
background: BACKGROUND This review was design ed to assess the evidence from r and omized controlled trials on effects of probiotics in the treatment and prevention of acute infectious diarrhea in infants and children .