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Probiotics and antibiotics in inflammatory bowel disease.

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease. Manipulation of the luminal content using antibiotics and/or probiotics may represent a potentially effective therapeutic option. Results of antibiotic treatment in inflammatory bowel disease are controversial, but this approach is frequently and successfully adopted in clinical practice. Recent data support the potential therapeutic role of probiotics in inflammatory bowel disease. In particular, a highly concentrated probiotic preparation was shown to be superior to placebo both on the prevention of pouchitis onset and of chronic pouchitis relapse. Its role in the maintenance treatment of ulcerative colitis and Crohn disease needs to be further assessed by large, double-blind, controlled trials. Future research needs to be focused on obtaining more precise information on the enteric microflora and the mechanisms of action of probiotics.

Journal Article↗

A clinical trial of probiotic administration for prevention of Salmonella shedding in the postoperative period in horses with colic.

The purpose of this study was to evaluate the effects of probiotic administration on the prevalence of fecal shedding of Salmonella, the prevalence of postoperative diarrhea, the length of antimicrobial therapy, and the length of the hospitalization stay during the postoperative period in horses with colic. Two commercially available probiotics for horses were used in a double-blind prospective study of 200 horses undergoing surgery for colic. Probiotic or placebo was administered PO once a day for 7 days postoperatively, and fecal cultures for Salmonella were obtained daily for 10 days. After selection of 186 patients completing the treatment protocol, the results indicated that the commercial probiotic formulations had no effect on Salmonella shedding, prevalence of diarrhea, length of antimicrobial therapy, or length of hospitalization (P > .05). Twenty percent of the horses yielded 1 or more positive fecal cultures for Salmonella; of these horses, 74% were classified as asymptomatic shedders. Twenty-six percent of all horses had fluid diarrhea postoperatively, with only 12% of these horses having positive fecal cultures for Salmonella. The most common isolate was Salmonella krefeld (24 of 39 isolates). Among the different gastrointestinal disorders, horses with feed and sand impactions appeared to be more prone to shed Salmonella.

Animal Feed↗

NF-kappaB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium.

Little is known about the defensive mechanisms induced in epithelial cells by pathogenic versus probiotic bacteria. The aim of our study was to compare probiotic bacterial strains such as Escherichia coli Nissle 1917 with nonprobiotic, pathogenic and nonpathogenic bacteria with respect to innate defense mechanisms in the intestinal mucosal cell. Here we report that E. coli strain Nissle 1917 and a variety of other probiotic bacteria, including lactobacilli--in contrast to more than 40 different E. coli strains tested--strongly induce the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) in Caco-2 intestinal epithelial cells in a time- and dose-dependent manner. Induction of hBD-2 through E. coli Nissle 1917 was further confirmed by activation of the hBD-2 promoter and detection of the hBD-2 peptide in the culture supernatants of E. coli Nissle 1917-treated Caco-2 cells. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-kappaB and AP-1 in the hBD-2 promoter are required for induction of hBD-2 through E. coli Nissle 1917. Treatment with the NF-kappaB inhibitor Helenalin, as well as with SP600125, a selective inhibitor of c-Jun N-terminal kinase, blocked hBD-2 induction by E. coli Nissle 1917 in Caco-2 cells. SB 202190, a specific p38 mitogen-activated protein kinase inhibitor, and PD 98059, a selective inhibitor of extracellular signal-regulated kinase 1/2, were ineffective. This report demonstrates that probiotic bacteria may stimulate the intestinal innate defense through the upregulation of inducible antimicrobial peptides such as hBD-2. The induction of hBD-2 may contribute to an enhanced mucosal barrier to the luminal bacteria.

Binding Sites↗

Survival of Lactobacillus acidophilus and Bifidobacterium bifidum in ice cream for use as a probiotic food.

Probiotic ice cream was made by fermenting a standard ice cream mix with Lactobacillus acidophilus and Bifidobacterium bifidum cultures and then freezing the mix in a batch freezer. Survival of the L. acidophilus and B. bifidum, as well as beta-galactosidase activity, was monitored during 17 wk of frozen storage at -29 degrees C. After freezing of the fermented mix, bacterial counts were 1.5 x 10(8) cfu/ml for L. acidophilus and 2.5 x 10(8) cfu/ml for B. bifidum. Seventeen weeks after freezing, these counts had decreased to 4 x 10(6) and 1 x 10(7) cfu/ml, respectively. During the same period, beta-galactosidase activity decreased from 1800 to 1300 units/ml. Probiotic ice cream was prepared at pH 5.0, 5.5, and 6.0 to determine consumer preferences and was compared with standard Utah State University "Aggie" ice cream. All samples were strawberry-flavored and were evaluated by 88 judges. The preferred pH of probiotic ice cream, based on overall acceptance, was pH 5.5. We demonstrated that probiotic ice cream is a suitable vehicle for delivering beneficial microorganisms such as L. acidophilus and B. bifidum to consumers. The bacteria can be grown to high numbers in ice cream mix and remain viable during frozen storage.

Animals↗

Plasma proteins and a probiotic as ingredients in milk replacer.

Milk replacers containing all milk protein, 25% of protein from porcine plasma protein, 25% of protein from bovine plasma protein, or all milk protein plus probiotic were compared in a 6-wk experiment using 120 Holstein bull calves approximately 7 d of age. All replacers contained an antibiotic except the one that contained probiotic. Calf starter always was available, and calves were weaned when they consumed 680 g/d of starter. Ten calves were selected randomly from each group for sampling of jugular blood at d 1 and 10 of the experiment. A complete blood count was conducted on the samples, and protein fractionation by electrophoresis was performed on sera harvested from the samples. Mean BW gains started to differ at the end of wk 3, and by the end of wk 6 the difference of 2.6 kg was significantly greater for those calves fed porcine or bovine plasma than for calves fed all milk protein (with or without probiotic). The same response was noted for starter consumption; the difference increased to 4.15 kg by the end of wk 6. Most measurements of blood did not differ by treatment; those that were different did not suggest an apparent difference in performance response. Growth performance of calves fed probiotic was not different from that of calves fed antibiotic when both replacers contained all milk protein. Either porcine or bovine plasma protein was an acceptable source of protein.

Animal Feed↗

Influence of whey and probiotic-supplemented withdrawal feed on the retention of Salmonella intubated into market age broilers.

Broilers (6 wk of age) were crop-intubated with a nalidixic acid-resistant strain of Salmonella typhimurium and given four withdrawal feeds: 1) control feed (corn and soybean meal base, 18% CP and 3,200 kcal ME/kg); 2) control plus 5% whey (61% lactose); 3) control plus probiotic (6.8 x 10(6) cfu of Bifidobacterium pseudolongum, Bifidobacterium thermophilium, and Lactobacillus acidophilus); and 4) control plus 5% whey plus probiotic. In Experiment 1, male broilers received 9.8 x 10(7) cfu of S. typhimurium per bird midway through a 20-h fast. The withdrawal feeds were continuously offered through a subsequent period of 6 to 7 days. Live performance of broilers during this time was similar among treatments. Ceca from birds consuming whey were significantly (P less than .05) increased in weight and distended with gas. Recovery of S. typhimurium from the ceca was low with all treatments, and the effects of whey or probiotic at reducing the organism could not be determined. In Experiment 2, female broilers received the same four experimental feeds for 48 h. Salmonella typhimurium was intubated 24 h after feed access (1.2 x 10(7) cfu per bird). Again, no differences (P greater than .05) in performance occurred, but the inclusion of whey led to increased cecal weight and size (P less than .05). Large numbers of S. typhimurium were recovered from the ceca 24 h after intubation, but the levels were similar among treatments. Whey and probiotic in the withdrawal feed did not appear to affect the Salmonella level in ceca when the organism was consumed prior to marketing.

Animal Feed↗

Bacterial metabolite patterns of infants receiving multi-strain probiotics and risk of late-onset sepsis.

The effect of multi-strain probiotics containing Bifidobacterium longum (B. longum) on late-onset sepsis (LOS) risk in very-low-birth-weight infants (VLBWIs; birth weight < 1,500 g) remains uncertain. In a single-center study, we analyzed intestinal metagenome and metabolome data in VLBWIs during the period of highest vulnerability of LOS. Using a unit's policy change to routinely administer B. longum subspecies infantis plus Lactobacillus acidophilus as natural experiment, we compared 97 infants (including 38 LOS cases) after change with 78 infants (including 32 LOS cases) before. Probiotic supplementation was associated with more beneficial bacteria and reduced abundance of nosocomial pathobionts, such as Klebsiella spp. Infants in the probiotic group had significantly lower concentrations of B. longum fermentation products prior to sepsis diagnosis than matched non-LOS cases (acetate: padj = 0.0049; lactate: padj = 0.048). Modulation of the gut metabolic milieu is an interesting target for LOS prevention.

Humans↗

Effects of Lactiplantibacillus plantarum KABP051 Probiotic on Body Composition, Microbiome and Mood in Healthy Overweight Adults.

Obesity and mental health disorders are among the greatest public health challenges of the 21st century. Interestingly, an altered microbiome profile has been associated with both conditions. The aim of this randomized, double-blind, placebo-controlled clinical trial was to evaluate the effects of dietary supplementation with a specific probiotic strain (Lactiplantibacillus plantarum KABP051) on body composition and gut microbiome balance, together with measures of mood state, in a population of healthy overweight subjects. Sixty healthy, moderately stressed, nondepressed and overweight or obese volunteers were supplemented for 12 weeks with probiotic (L. plantarum KABP051; 1 billion colony forming units/day) or placebo (microcrystalline cellulose). The KABP051 group experienced significantly greater improvements compared with placebo on body composition measurements, including a reduction in body weight and waist circumference, which decreased in 1.97 &#xb1; 0.77 (mean &#xb1; SE) kg and 2.15 &#xb1; 0.81 (mean &#xb1; SE) cm versus placebo at the end of the intervention (both P < .05, mixed model for repeated measures [MMRM] and post-hoc analysis). Microbiome composition improved in KABP051 group, with significant increase in the relative abundance of Lactiplantibacillus spp. versus placebo. Body fat percentage, profile of mood states fatigue, and confusion sub-scores showed a global trend toward improvement compared with placebo, with the change at 12 weeks being significant in the three measurements in post-hoc analysis (P = .015, P = .014, and P = .016, respectively). No serious adverse events were registered during the intervention period. These results suggest that a specific strain of probiotic bacteria (L. plantarum KABP051) may have both metabolic and psychobiotic effects and may be beneficial for enhancing weight loss and body composition, improving energy (less fatigue) and mood levels while embarking on a healthy lifestyle regimen. ClinicalTrials.gov identifier: NCT06808061.

Humans↗

Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo-caecal resection.

BACKGROUND: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD. METHODS: Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. RESULTS: Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79). CONCLUSION: Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.

Adolescent↗

Use of group-specific and RAPD-PCR analyses for rapid differentiation of Lactobacillus strains from probiotic yogurts.

The increasing interest in probiotic lactobacilli implicates the requirement of techniques that allow a rapid and reliable identification of these organisms. In this study, group-specific PCR and RAPD-PCR analyses were used to identify strains of the Lactobacillus casei and Lactobacillus acidophilus groups most commonly used in probiotic yogurts. Group-specific PCR with primers for the L. casei and L. acidophilus groups, as well as L. gasseri/johnsonii, could differentiate between 20 Lactobacillus strains isolated from probiotic yogurts and assign these into the corresponding groups. For identification of these strains to species or strain level, RAPD profiles of the 20 Lactobacillus strains were compared with 11 reference strains of the L. acidophilus and L. casei group. All except one strain could be attributed unambigously to the species L. acidophilus, L. johnsonii, L. crispatus, L. casei, and L. paracasei. DNA reassociation analysis confirmed the classification resulting from the RAPD-PCR.

DNA, Bacterial↗

Probiotics to prevent urinary tract infections: the rationale and evidence.

For over 30 years, urologists have recognized in females, that urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Likewise, the Lactobacillus organisms that predominate in the vagina of healthy women, spread from the rectum and perineum and form a barrier in the vagina to bladder entry by uropathogens. The concept of artificially boosting the lactobacilli numbers through probiotic instillation has long been conceived, but only in recent years shown to be possible. Not all lactobacilli are effective, and to date clinical efficacy only exists for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri B-54 and RC-14. These strains are only commercially available in Austria, and therefore for most urologists, while some probiotic organisms may reduce the recurrences of bladder cancer or oxaluria, no probiotics can be recommended widely to prevent UTI at present.

Administration, Intravaginal↗

The physiology of colonic metabolism. Possibilities for interventions with pre- and probiotics.

The awareness is increasing that in the colon many metabolic processes take place in relation to the fermentation of our food, which might be relevant for health and disease. However, the relation between food, colon metabolism and health or disease is far from clear. In this overview, the physiology of colonic metabolism and possibilities for its modification by the use of pre- and probiotics are discussed. Results of in vitro and animal studies indicate a beneficial impact of probiotics on adverse metabolic processes in the colon, but confirmation in human studies has to be extended. The administration of prebiotics seems to be promising with regard to their capacity to modulate the bacterial composition in the colon and there are indications that prebiotics can beneficially influence colonic metabolism. Whether these modulations brought about by pre- or probiotics have an effect on the health of the host, however, needs to be established in most cases.

Animals↗

Protection against translocating Salmonella typhimurium infection in mice by feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HN001.

The probiotic lactic acid bacterium Lactobacillus rhamnosus (strain HN001) is known to stimulate enhanced innate and acquired immune responses in mice. following oral delivery. Here, the ability of HN001 to confer immune enhancement and protection against an oral challenge of Salmonella tYphimurium was investigated. HN001-fed and non-probiotic-fed control BALB/c mice were challenged with either a single dose of S. typhimurium (ATCC strain 1772), or with five repeated daily doses of the pathogen; post-challenge clinical, behavioural, bacteriological and immunological parameters were assessed. Mice began to show ostensible signs of infection 3-4 days following the initiation of Salmonella challenge, and the first mortalities were observed after 6 days. Following single-dose Salmonella challenge, HN001-fed mice maintained a higher mean pre-mortality general health score than control mice; retained significantly greater food and water intake and weight gain, produced higher titres of serum and intestinal tract anti-Salmonella antibodies, and showed greater overall survival of infection (27/30 mice surviving at 21 days post-challenge, compared to 2/29 in the control group). Following repeated-dose Salmonella challenge, HN001-fed mice had significantly lower mean pathogen burdens in visceral organs (spleen, liver) compared to controls, and additionally, blood and peritoneal leucocytes obtained from HN001-fed mice exhibited significantly higher ex vivo phagocytic capacity compared to control-mice. This study affirms that Lb. rhamnosus strain HN001 displays immuno-enhancing properties in S. typhimurium-infected mice, and demonstrates that oral delivery of this probiotic can promote increased protection against a highly virulent enteric bacterial pathogen.

Animals↗

Experimental study of the effects of probiotics on Cryptosporidium parvum infection in neonatal rats.

To date, there is no efficient treatment for cryptosporidiosis and parasite eradication relies on innate and acquired immunity. In this study, we investigated the effect of administration of probiotic bacteria on the development and progression of the experimental infection in suckling rats. Rats were fed daily with 2.10(7) CFU of Lactobacillus casei-containing mixture, starting 2 days before the infection until the spontaneous clearance of the parasite. Effects on weight gain, parasite burden, mucosal histology and production of mucosal cytokines (IFNgamma, IL10 and TNFalpha) were studied. Although a trend to a more rapid clearance of parasites was noted in rats treated with probiotics, no significant effect of probiotics administration was observed in terms of weight gain, parasite burden, mucosal damage, or kinetics of mucosal cytokines during the course of infection. Overall, our results showed that the daily administration of L. casei-containing mixtures was unable to eradicate the parasite in our model.

Animals↗

Histological changes in intestine of Atlantic salmon (Salmo salar L.) following in vitro exposure to pathogenic and probiotic bacterial strains.

Furunculosis and vibriosis are diseases that cause severe economic losses in the fish-farming industry. The foregut of the Atlantic salmon (Salmo salar L.) was exposed in vitro to two fish pathogens, Aeromonas salmonicida (causative agent of furunculosis) and Vibrio anguillarum (causative agent of vibriosis), and to one probiotic strain, Carnobacterium divergens, at 6 x 10(4) or 6 x 10(6) viable bacteria per milliliter. Histological changes following bacterial exposure were assessed by light and electron microscopy. Control samples (foregut exposed to Ringer's solution only) and samples exposed only to C. divergens had a similar appearance to intact intestinal mucosal epithelium, with no signs of damage. However, exposure of the foregut to the pathogenic bacteria resulted in damaged epithelial cells, cell debris in the lumen, and disorganization of the microvilli. Co-incubation of the foregut with a pathogen and C. divergens did not reverse the damaging effects caused by the pathogen, although these were alleviated when probiotic bacteria were used. Based on these results, we suggest that the probiotic bacterium, C. divergens, is able to prevent, to some extent, pathogen-induced damage in the Atlantic salmon foregut.

Aeromonas salmonicida↗

Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Phase II study.

Febrile neutropenia (FN) remains a potentially life-threatening complication of anticancer chemotherapy. Bacterial translocation via intestinal mucosa is a significant mechanism of FN development. Competitive inhibition of bowel colonization by pathogenic microorganisms by lactic acid bacteria could be a useful prevention of FN. The aim of the study was the prevention of FN by probiotic strain Enterococcus faecium M-74 enriched with selenium in leukemic patients. Fourteen (six males/eight females) patients with myelogenous leukemia treated by induction or consolidation chemotherapy were included in the study. Patients received prophylaxis with E. faecium M-74 during one cycle of chemotherapy. The daily dose was 36 x 10(9) CFU tid. Prophylaxis started between day -2 and day +2 of chemotherapy and continued until the absolute neutrophile count (ANC) was >1,000/microl. All patients experienced febrile neutropenia. During 231 days of severe neutropenia, 30 febrile episodes occurred. No any febrile episode or infection provoked by the strain tested was noticed. Tolerance of therapy was excellent without significant adverse effects. Our results demonstrate the safety of the probiotic strain E. faecium M-74 enriched with selenium in leukemic patients with severe neutropenia. However, its administration was not effective in the prevention of febrile neutropenia, but this does not preclude the protective effect of other probiotic strains.

Adult↗

Effect of probiotic supplementation on bacterial translocation in thermal injury.

PURPOSE: To examine the effects of probiotic supplementation and enteral solutions containing glutamine and arginine on bacterial translocation (BT) and intestinal villous atrophy in thermal injury. METHODS: Forty male Sprague-Dawley rats weighing 200-250 g were divided into four groups of ten. Group 1 served as control group without thermal injury and was fed standard chow. Thermal injury was inflicted as a 30% scald burn in the other three groups. Group 2 was fed standard chow and group 3 was fed standard chow supplemented with a probiotic (Acidophilus plus) containing Bifidobacterium bifidum, Lactobacillus acidophilus, and Lactobacillus bulgaricus (2 x 10(9) CFU/day) via an orogastric tube. Group 4 was fed only an enteral diet (Stresson multifiber) containing glutamine, arginine, and medium chain triglyceride, at 1 g/kg per day amino acid and 230 kcal/kg, for 7 days before thermal injury. All the animals were killed 24 h after thermal injury, and ileal segments were resected and examined histopathologically. To evaluate BT, samples from blood, mesenteric lymph nodes, and cecal content were cultured under aerobic and anaerobic conditions. Terminal ileum specimens were histologically examined to evaluate mucosal integrity. RESULTS: Significantly less BT was seen in groups 3 and 4 than in group 2 (P < 0.001). No significant difference was found between groups 3 and 4. Histological evaluation showed significant reduction in villous atrophy in groups 3 and 4. CONCLUSION: Probiotic supplementation seems to reduce bacterial translocation and decrease intestinal mucosal atrophy in rats with thermal injury, as do enteral solutions with arginine and glutamine.

Analysis of Variance↗

Anti-inflammatory effect of bioflora probiotic administered orally or subcutaneously with live or dead bacteria.

The anti-inflammatory effect of Bioflora probiotic administered orally or subcutaneously with viable or nonviable bacteria was analyzed in two experimental models of randomly selected female Wistar rats. The use of indomethacin at a dose of 50 mg/kg was associated with gastric necrotic lesions and multiple erosions of the small intestine, with marked mucosal neutrophil infiltrate measured by myeloperoxidase (MPO). Probiotics prevented both gastrointestinal lesions and neutrophil infiltrate (p < 0.001). In the model of carrageenin-induced plantar edema in the rat, the oral or subcutaneous administration of Bioflora with live or dead bacteria proved to prevent plantar edema (p < 0.001). We concluded that Bioflora probiotic given orally or subcutaneously with live or dead bacteria has an anti-inflammatory effect.

Administration, Oral↗