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Efficacy of probiotics and nutrients in functional gastrointestinal disorders: a preliminary clinical trial.

The purpose of this study was to evaluate the efficacy and safety of commonly used probiotics and nutrients available for functional gastrointestinal disorders (FGID). Five different combinations of probiotics and nutrients, or placebo, were taken daily over 12 weeks. In this randomized controlled clinical trial, men and women 21 to 72 years of age with FGID symptoms of indigestion, bloating, and abdominal discomfort were assigned to one of six groups, 12 patients per group. Gastrointestinal Quality of Life Index (GIQLI) and visual analogue scale (VAS) for GI symptoms, SF-36, lactulose and mannitol test (LMT), and urine indican levels were evaluated. GIQLI, VAS scores, and LMT did not change significantly (P > 0.05). There were clinically notable improvements in two of the combination formulations. While the nonsignificant improvements in GI symptoms could suggest that combination probiotics and nutrients may be beneficial in conditions such as FGID, no conclusive evidence was found in this pilot trial. Further investigations to explore the findings are discussed.

Abdominal Pain↗

Probiotics in clinical conditions.

Probiotics are nonpathogenic microorganisms which, when ingested, exert a positive influence on the health or physiology of the host. Their mechanisms of action and effects are now studied using the same pharmacological approach as for drugs. This article summarizes and comments on evidence for the positive effects of probiotics in various clinical situations. Substantial evidence can be achieved when randomized controlled trials or meta-analyses show positive results. The clinical situations studied include prevention or treatment of antibiotic-associated disorders, gastroenteritis, and diarrhea, lactose intolerance, intestinal infections and colonization by pathogenic bacteria (including Helicobacter pylori and Clostridium difficile), traveler's diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic cancer, urogenital infections and tumors, allergy (especially atopic eczema), vaccination, and cholesterol lowering. Current probiotics have an excellent safety record--another topic discussed in this article.

Bifidobacterium↗

Evaluation of Indigenous Bacillus Strains from Asian Fermented Foods for Probiotic Properties.

Bacillus species hold particular importance due to their versatile enzymatic repertoire and ability to synthesize diverse bioactive metabolites. In this study, two fermented food-derived strains, Bacillus siamensis BB3 (from douchi) and Bacillus velezensis TMA10 (from tapai) were evaluated for their probiotic, anti-microbial and functional potentials. Both strains exhibited desirable probiotic characteristics, including desirable tolerance to simulated gastric and intestinal conditions, with BB3 showing greater acid tolerance than TMA10. Safety assessments confirmed the absence of hemolytic activity, virulence factors and antibiotic resistance genes. Whole genome sequencing showed that the strains harbored genomic sequences for a wide range of metabolites, including non-ribosomal peptides and polyketides. Ethyl acetate (EtOAc) extracts from both strains demonstrated broad-spectrum anti-microbial activity against several indicator microorganisms, including Listeria grayi, Bacillus cereus, Serratia marcescens, Escherichia coli, and Pseudomonas aeruginosa, with TMA10 additionally inhibiting MRSA and Streptococcus mutans. Liquid Chromatography-Mass Spectrometry profiling identified key anti-microbial compounds, namely surfactins, macrolactins, bacillaene from BB3 and TMA10. In addition, difficidins were also detected from TMA10. Genomic analysis further indicated diverse carbohydrate utilization capacities; both strains encoded pathways for sucrose, raffinose-family oligosaccharides and lactose metabolism, while TMA10 possessed pathways for trehalose, glucomannan and arabinoxylan degradation. Both strains also showed anti-oxidant activity, with enhanced effects observed in their cell-free supernatants and heat-killed preparations. Overall, these findings highlight BB3 and TMA10 as promising candidates for the development of fermented food-derived Bacillus probiotics and functional cultures with anti-microbial, anti-oxidant, and broad carbohydrate-utilization capabilities.

Bacillus↗

A dietary probiotic (Bifidobacterium lactis HN019) reduces the severity of Escherichia coli O157:H7 infection in mice.

The protective effects of the probiotic Bifidobacterium lactis HN019 against Escherichia coli O157:H7 were investigated in murine challenge infection models. BALB/c or C57BL/6 mice were fed milk-based diets supplemented with B. lactis HN019 (3 x 10(8) cfu/g) for 7 days prior to and following oral challenge with E. coli O157:H7. Behavioral parameters (morbidity, feed intake) were measured for 7 days following challenge; immunological responses (phagocytosis, antibody) and pathogen translocation were measured in a sub-sample of ostensibly healthy animals 1 week post-challenge. Results showed that HN019-fed mice maintained significantly higher post-challenge feed intake and exhibited a lower cumulative morbidity rate, compared to control mice which did not receive the probiotic. Significantly higher proportions of phagocytically active cells in the blood and peritoneum, and higher intestinal tract IgA anti-E. coli antibody responses, were recorded among HN019-fed mice compared to controls. Among HN019-fed mice, pathogen translocation was identified in one of five BALB/c and one of five C57 mice; the comparative figures in control mice were two of five and three of five, respectively, and the mean bacterial burdens in these mice were over 100-fold higher than in HN019-fed mice. These results demonstrate that HN019 can reduce the severity of infection due to the enterohemolytic pathogen E. coli O157:H7, and suggest that this reduction may be associated with enhanced immune protection conferred by the probiotic.

Animals↗

Application of potential probiotic Lactobacillus fermentum AD1 strain in healthy dogs.

Probiotic utilization is becoming increasingly popular in veterinary medicine. However, only few probiotic products are available commercially for use in dogs in our market. Therefore, the aim of our study was to determine the properties of new potential probiotic Lactobacillus fermentum AD1 strain-own canine isolate and to investigate its effect on several microbiological and biochemical parameters in healthy dogs. The strain expressed in vitro survival by pH 3.0 after 3h (86.8%) and in the presence of 1% bile (75.4%). The AD1 strain adhered to the canine and human intestinal mucus. It was sensitive to commonly used antimicrobials. Fifteen healthy dogs were supplemented with 10(9)L. fermentum AD1 for 7 days. At the end of AD1 strain application, numbers of faecal lactobacilli and enterococci increased significantly in the canine faeces. Significant increase of total protein and total lipid and significant reduction of glucose in serum of dogs were noted. These data indicate that L. fermentum AD1 survive transit through the canine gastrointestinal tract, and populate the colon and probably increased absorption of some nutrients. Whether longer time of its application lead to the same results as well as its potential to improve immune function in dogs remains to be determined.

Animals↗

[Evaluation of a formula with low protein content and supplemented with probiotic agents after breast milk weaning].

UNLABELLED: Besides assuring growth and development in early infancy, human breast milk plays a key role in preventing infections, in particular by favouring the growth of bifidobacteria. The development of infant formulas containing probiotic agents consequently represents a significant advance in the provision of an optimal alternative to breast feeding when this is not feasible. A further concern is to avoid an excessively high protein content relative to breast milk, potentially favouring obesity in later life. OBJECTIVES: The objective of this open Multicenter comparative study was to demonstrate that a new infant formula, characterized by a reduced protein content and the presence of a probiotic agent, was as effective as conventional formulas in assuring growth during the first months of life. POPULATION AND METHODS: The study population comprised full-term healthy infants with an age at inclusion of 1-28 days, whose mothers no longer wished to continue breast feeding or were unable to breast feed. The test formula (GE), enriched with Bifidobacterium lactis, had a protein content of 1.5 g/100 ml. The primary end point was daily weight gain from day 0 to day 90. Secondary end points were daily increase in height and cranial circumference, overall and gastrointestinal tolerance and formula acceptability. A total of 203 infants were included in the analysis, 117 receiving GE and 86 the formula habitually prescribed by the paediatrician. RESULTS: Daily gains in weight, height and cranial circumference did not differ significantly between the groups. The rates of overall and gastrointestinal adverse events were comparable in the two groups and the acceptability of GE was consistently good, similar to that of the standard formulas. CONCLUSION: The results of this study demonstrated that the new probiotic infant formula GE has equivalent efficacy to conventional formulas in achieving growth in early infancy, and is well tolerated.

Bifidobacterium↗

Probiotics in the prevention and treatment of gastrointestinal infections.

Probiotics have been studied in a variety of GI infections, and are an appealing concept given their favorable safety profiles. Several placebo-controlled trials indicated that lactobacilli have a suppressive effect on H pylori infection. Although some studies reported improvement in H pylori eradication, others failed to confirm this. Controlled trials support the use of Lactobacillus GG and S boulardii for the prevention of AAD, and have demonstrated the effectiveness of S boulardii as adjunctive therapy for RCDAD. Several placebo-controlled trials showed a reduction in the severity and duration of acute diarrhea in children with use of Lactobacillus GG. Studies of probiotics for the prevention of traveler's diarrhea yielded conflicting results, and their routine use cannot be recommended in this setting. Preliminary evidence suggests a potential role for reducing secondary pancreatic infections, although conclusive evidence is not available at this time. Additional clinical trials are indicated to define the role of probiotics further before wide-spread use can be recommended.

Anti-Bacterial Agents↗

Effects of anti-Helicobacter pylori treatment and probiotic supplementation on intestinal microbiota.

The aims of this study were (i) to evaluate the effect of recommended antimicrobial treatment of Helicobacter pylori infection, consisting of clarithromycin, amoxicillin and lansoprazole, on intestinal microbiota and (ii) to determine the ability of a probiotic combination containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 to prevent treatment-induced alterations in the intestinal microbiota. Faecal samples were obtained from 39 H. pylori-infected patients randomised into two treatment groups. In addition, 19 H. pylori-negative volunteers were included in the study as a control group. Samples were collected before, during and after treatment and microbiota were analysed by fluorescence in situ hybridisation and culture. The quantities of the predominant bacterial groups were altered significantly in both groups and disturbances were seen even 9 weeks after treatment was complete. Probiotics slightly counteracted the effects of anti-H. pylori treatment, seen as significantly less alterations in the total numbers of aerobes and lactobacilli/enterococci. At baseline, the composition of the microbiota between H. pylori-positive versus H. pylori-negative control individuals differed with regard to clostridia and the total number of anaerobes. The recommended treatment for H. pylori infection induces long-term disturbances in the intestinal microbiota. The probiotic combination appeared to result in only minor changes in the microbiota.

2-Pyridinylmethylsulfinylbenzimidazoles↗

In vitro screening of probiotic properties of Saccharomyces cerevisiae var. boulardii and food-borne Saccharomyces cerevisiae strains.

The probiotic potential of 18 Saccharomyces cerevisiae strains used for production of foods or beverages or isolated from such, and eight strains of Saccharomyces cerevisiae var. boulardii, was investigated. All strains included were able to withstand pH 2.5 and 0.3% Oxgall. Adhesion to the nontumorigenic porcine jejunal epithelial cell line (IPEC-J2) was investigated by incorporation of 3H-methionine into the yeast cells and use of liquid scintillation counting. Only few of the food-borne S. cerevisiae strains exhibited noteworthy adhesiveness with the strongest levels of adhesion (13.6-16.8%) recorded for two isolates from blue veined cheeses. Merely 25% of the S. cerevisiae var. boulardii strains displayed good adhesive properties (16.2-28.0%). The expression of the proinflammatory cytokine IL-1alpha decreased strikingly in IPEC-J2 cells exposed to a Shiga-like toxin 2e producing Escherichia coli strain when the cells were pre- and coincubated with S. cerevisiae var. boulardii even though this yeast strain was low adhesive (5.4%), suggesting that adhesion is not a mandatory prerequisite for such a probiotic effect. A strain of S. cerevisiae isolated from West African sorghum beer exerted similar effects hence indicating that food-borne strains of S. cerevisiae may possess probiotic properties in spite of low adhesiveness.

Animals↗

Application of in vitro methods for selection of Lactobacillus casei strains as potential probiotics.

Probiotics have established their efficacy as dietary adjuncts providing benefits to consumers, but the selection of probiotics before incorporation in diet requires close scrutiny in the form of in vitro as well as in vivo tests. The present study was undertaken to check different in vitro characteristics of seven Lactobacillus casei strains. The characteristics studied include acid and bile tolerance, adhesion and cell surface hydrophobicity, antimicrobial effect on common pathogens and cholesterol reduction. All strains were able to resist pH 3 for 3 h, though resistance to pH 2 was exhibited by NCDC 17, C1 and Y strains only. NCDC 63 and VT strains were able to tolerate 1% and 2% bile concentrations for 12 h. There was wide variation in ability of strains to adhere to isolated rat epithelial cells. The index was highest for C1 at 66%. The electron microscopic adhesion studies on the stainless steel chips did not reveal any specific attachment to surfaces by any of strains. The hydrophobic character for octane was highest for strain C1 at 54.06% and lowest for strain C2 at 4.65%. The ability to antagonize common pathogens was observed in all strains but this activity was attributed to production of organic acids and no specific compound caused the inhibitory effect. The cholesterol reducing ability varied not only for strains but also for time of incubation. NCDC 17 showed maximum reduction in cholesterol level after 48 h of incubation with buffalo plasma as the source of cholesterol. Overall there existed variations in different strains with respect to different characters of significance to be a probiotic.

Adaptation, Physiological↗

Molecular tools for differentiating probiotic and clinical strains of Saccharomyces cerevisiae.

The subtype of the Saccharomyces cerevisiae yeast species known as S. cerevisiae Hansen CBS 5926 was formerly believed to be a separate species, Saccharomyces boulardii. It is widely considered non-pathogenic and is used as a probiotic agent for treatment and prevention of diarrhea. The biological properties of Saccharomyces spp. show considerable intraspecies variability and the beneficial properties of probiotic yeasts are considered strain-specific. Septicemia and fungemia caused by S. boulardii have recently been described in both immunocompromised and immunocompetent patients receiving biotherapy with this yeast. It cannot be distinguished from other S. cerevisiae strains by phenotypic criteria, so identification of these infections requires molecular typing. To identify the most effective approach for distinguishing S. boulardii, we typed 35 isolates of S. cerevisiae, of which 27 were from various clinical specimens and 8 were isolates of S. boulardii (6 obtained from probiotic preparations and 2 from clinical specimens) using four different molecular methods, two based on PCR-restriction enzyme analysis or sequencing of rDNA spacer regions, the third based on microsatellite polymorphism analysis of the S. cerevisiae genes YKL139w and YLR177w, and the last based on hybridization analysis with retrotransposon Ty917. Several clinical isolates appeared to be identical to one or more other isolates with the first three methods used, whereas with the Ty917 hybridization method all of the isolates tested appeared to be very heterogeneous. The eight S. boulardii isolates were clearly distinguishable from the clinical S. cerevisiae isolates only with Ty917 hybridization and microsatellite DNA analyses. In the latter method, the eight S. boulardii isolates exhibited an allelic variant at one of loci tested that was not shared with any other strain. Our results suggest that microsatellite polymorphism analysis of the YKL139w and YLR177w genes, as well as the analysis by Ty917 hybridization, are the most useful tools for a correct identification of S. boulardii strains.

Blotting, Southern↗

Effect of Bifidobacterium thermacidophilum probiotic feeding on enterohemorrhagic Escherichia coli O157:H7 infection in BALB/c mice.

The effectiveness of Bifidobacterium thermacidophilum RBL 71 as a probiotic against enterohemorrhagic Escherichia coli O157:H7 infection was studied using a murine model. BALB/c mice were fed the probiotic for 7 days before or after single challenge with E. coli O157:H7. Fecal B. thermacidophilum RBL 71 and E. coli O157:H7 counts obtained by selective culturing methods were assessed for 1 week before and after infection while feed intake, body weight and composition were monitored during 1 week after infection. Histology of gut tissue (jejunum, ileum and colon) and production of fecal IgA antibodies and serum IgG+IgM antibodies to E. coli O157:H7 were analyzed until 1 and 2 weeks post-infection, respectively. The pathogenicity of E. coli O157:H7, marked by body weight loss and intestinal histopathological changes in the infected group, was significantly reduced in the B. thermacidophilum-treated group. Feeding B. thermacidophilum RBL 71 for 7 days before infection resulted in greater post-challenge feed intake and weight gain and lower fecal levels of E. coli O157:H7. Post-infection levels of anti-E. coli O157:H7-specific IgA in feces and IgG+IgM in serum were higher in mice fed bifidobacteria. Intestinal injuries were also attenuated and reaction of the lymphoid component in the mucosa of the ileum was greater in the bifidobacteria-fed group. A lesser degree of protection against E. coli O157:H7 infection was observed when bifidobacteria were given during the 7 days after E. coli O157:H7 infection. These results demonstrate that feeding the probiotic B. thermacidophilum RBL 71 to mice can reduce the severity of E. coli O157:H7 infection, and suggest that this strain represents a good candidate for the prevention of enteric infections in human.

Animals↗

Evaluation of real-time PCR targeting the 16S rRNA and recA genes for the enumeration of bifidobacteria in probiotic products.

The application of real-time PCR targeting the multicopy 16S rRNA gene and the single copy recA gene was evaluated for the enumeration of bifidobacteria in 29 probiotic products claimed to contain these organisms. Both assays relied on the use of genus-specific primers and the non-specific SYBR Green I chemistry. For both applications, the calibration curve was constructed using the type strain of Bifidobacterium animalis subsp. lactis. Upon correction with a factor corresponding to the 16S rRNA gene copy number, both assays generally produced comparable enumeration results. Only in exceptional cases, differences between both gene targets were found in probiotic products containing low amounts of bifidobacteria in which case the quantification of the multicopy 16S rRNA gene turned out to be more sensitive than the recA-based assay. On the other hand, the use of the latter single copy gene in real-time PCR quantification offers the advantage that no prior knowledge of bacterial content is required when using genus-specific primers, since no correction for multiple gene copies has to be performed. Only 11 of the analysed products (38%), including one dairy based product and ten dried products, contained a minimal Bifidobacterium concentration of 10(6) CFU per ml or g of product. Depending on the application, both assays proved to be rapid and reproducible alternatives for culture-based detection and quantification of bifidobacteria in probiotic products.

Benzothiazoles↗

Genomic peculiarity of coding sequences and metabolic potential of probiotic Escherichia coli strain Nissle 1917 inferred from raw genome data.

Probiotic Escherichia coli strain Nissle 1917 (O6:K5:H1) is a commensal E. coli isolate that has a long tradition in medicine for the treatment of various intestinal disorders in humans. To elucidate the molecular basis of its probiotic nature, we started sequencing the genome of this organism with a whole-genome shotgun approach. A 7.8-fold coverage of the genomic sequence has been generated and is now in the finishing stage. To exploit the genome data as early as possible and to generate hypotheses for functional studies, the unfinished sequencing data were analyzed in this work using a new method [Sun, J., Zeng, A.P., 2004. IdentiCS--identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence. BMC Bioinformatics 5, 112] which is particularly suitable for the prediction of coding sequences (CDSs) from unannotated genome sequence. The CDSs predicted for E. coli Nissle 1917 were compared with those of all five other sequenced E. coli strains (E. coli K-12 MG1655, E. coli K-12 W3110, E. coli CFT073, EHEC O157:H7 EDL933 and EHEC O157:H7 Sakai) published to date. Five thousand one hundred and ninety-two CDSs were predicted for E. coli Nissle 1917, of which 1065 were assigned with enzyme EC numbers. The comparison of all predicted CDSs of E. coli Nissle 1917 to the other E. coli strains revealed 108 CDSs specific for this isolate. They are organized as four big genome islands and many other smaller gene clusters. Based on CDSs with EC numbers for enzymes, the potential metabolic network of Nissle 1917 was reconstructed and compared to those of the other five E. coli strains. Overall, the comparative genomic analysis sheds light on the genomic peculiarity of the probiotic E. coli strain Nissle 1917 and is helpful for designing further functional studies long before the sequencing project is completely finished.

Chromosome Mapping↗

Probiotic effects of beta-glucuronidase on the peach-potato aphid Myzus persicae (Aphididae).

beta-glucuronidase (GUS) is a reporter protein commonly expressed in transgenic plants allowing the visualization of the transformed individuals. In our recent work, we showed that consumption of transformed potato plants expressing this GUS enzyme improves performance of the phloem feeding aphid Myzus persicae. Those results led us to the conclusion that the expression of GUS in potato plants might be responsible for the probiotic effect measured in feeding aphids. In the present paper, artificial diets were used to provide active GUS (10 and 500 microg ml(-1)), inactivated heated GUS (500 microg ml(-1)), glucuronic acid (10, 100 and 500 microg ml(-1)), and bovine serum albumin (500 microg ml(-1)) to M. persicae. Our results reveal that these chemicals provided as food intake might influence the biological parameters of this aphid. Experiments showed a probiotic effect of 500 microg ml(-1) GUS diet, resulting in reduced larval mortality, and increased adult reproduction period and fecundity, which led to an increased population growth potential (r(m)=0.17+/-0.01 versus r(m)=0.12+/-0.03 for aphids fed on control diet). A lower amount of added GUS led to fewer variations, biological parameters being only slightly altered (r(m)=0.14+/-0.03). Statistically similar alterations of the biological parameters were obtained when comparing aphids fed on the diet added with inactivated GUS or the non-structural bovine serum albumin protein (r(m)=0.15+/-0.02 and 0.14+/-0.03, respectively). Feeding assays conducted with glucuronic acid supplemented diets enhanced longevity and nymph production of the adult aphids and reduced larval mortality, resulting in r(m)=0.15+/-0.02 for the highest dose (500 microg ml(-1)). Although 100 microg ml(-1) glucuronate diet did not induce any effect on M. persicae (r(m)=0.12+/-0.03), aphids fed on 10 microg ml(-1) glucuronate diet exhibited unexpected reduced demographic parameters (r(m)=0.10+/-0.03). Immuno-histological analysis showed GUS labeling along the whole digestive epithelium of adults and in various tissues including embryos and bacteriocytes. These results suggest that GUS crosses through the digestive tract. Western blots performed with protein extracts of transformed potato plants expressing the gus gene showed a unique band of molecular weight 76 kDa. On the contrary, in extracts from aphids fed on transgenic potato plants or bred on GUS 500 microg ml(-1) artificial diet, several proteins of lower molecular weight were hybridized, revealing proteolysis of ingested GUS. It is concluded that GUS protein, and more precisely GUS activity, is responsible for the probiotic effects on aphid feeding. The possible pathways of induction of such physiological alterations by GUS are discussed.

Animal Feed↗

Probiotics partly reverse increased bacterial translocation after simultaneous liver resection and colonic anastomosis in rats.

BACKGROUND: Bacterial translocation is one important cause of nosocomial infections following major abdominal surgery. Oral administration of probiotics has been proposed to diminish bacterial translocation. MATERIAL AND METHODS: In total 68 rats were divided into seven groups: five of the groups received standard rat chow and were subjected to either sham-operation, 70% liver resection, colonic anastomosis, or a combination of 30 or 70% liver resection with synchronous colonic anastomosis, respectively. In two additional groups with synchronous operation, a combination of four different lactic acid bacteria and four fibers was administered two times daily pre- and postoperatively. Bacterial concentrations in cecum, mesenteric lymph nodes, liver, and spleen were analyzed and blood cultures were taken 48 h after operation. Furthermore, the following parameters were assessed: histological changes in the intestine, intestinal paracellular permeability (Ussing chamber), bursting pressure of the colonic anastomosis, and mitosis rate of the remnant liver. RESULTS: Bacterial translocation was observed in all rats, except in the sham group. Following liver resection, the highest bacterial concentrations were seen in liver and spleen, following colon anastomosis in the mesenteric lymph nodes. Bacterial translocation was increased in the animals with combined operation, in parallel to the extent of liver resection. In rats with colon anastomosis, bacterial concentration in the cecum was also higher than in the sham group. Application of probiotics significantly decreased bacterial concentration in the lymph nodes. In addition, animals with a high cecal concentration of lactobacilli had less translocation than the others. No histological changes were observed in the intestine. Paracellular permeability for ions, but not for the larger molecule lactulose, was increased in the colon in all groups with colon anastomosis. The bursting pressure of the colon anastomosis was not significantly different between the groups. Seventy percent liver resection led to a high rate of hepatocyte mitosis, whereas combination with colon anastomosis impaired the regeneration process. CONCLUSION: Synchronous liver resection and colon anastomosis led to increased bacterial translocation compared to the single operations in the rat model. It is possible to diminish this process by oral administration of probiotics. Bacterial overgrowth in the cecum and impaired hepatic regeneration, but not histological changes or alterations of paracellular permeability, are potential pathogenic mechanisms for translocation in this setting.

Administration, Oral↗

Major depressive disorder: probiotics may be an adjuvant therapy.

Major depressive disorder (MDD) is an extremely complex and heterogeneous condition. Emerging research suggests that nutritional influences on MDD are currently underestimated. MDD patients have been shown to have elevated levels of pro-inflammatory cytokines, increased oxidative stress, altered gastrointestinal (GI) function, and lowered micronutrient and omega-3 fatty acid status. Small intestinal bacterial overgrowth (SIBO) is likely contributing to the limited nutrient absorption in MDD. Stress, a significant factor in MDD, is known to alter GI microflora, lowering levels of lactobacilli and bifidobacterium. Research suggests that bacteria in the GI tract can communicate with the central nervous system, even in the absence of an immune response. Probiotics have the potential to lower systemic inflammatory cytokines, decrease oxidative stress, improve nutritional status, and correct SIBO. The effect of probiotics on systemic inflammatory cytokines and oxidative stress may ultimately lead to increased brain derived neurotrophic factor (BDNF). It is our contention that probiotics may be an adjuvant to standard care in MDD.

Adjuvants, Immunologic↗

Preventive and curative effects of probiotics in atopic patients.

Normally, the transport of allergens through the intestinal epithelia to the blood is limited. It is hypothesised that if these compounds arrive in the blood circulation, they must percolate through the epithelial cell layer. Thus, food allergy (and thus atopic eczema) implies an increased intercellular leakage of the gut wall. Such increased intercellular leakage is thought to be caused by a slightly changed cellular morphology due to a slight cytopathologic effect because of both a limited decay of the cytoskeleton and a slightly reduced turgor. These events may be due to a reduced production of intracellular metabolic energy in the epithelial cells due to an increased concentration of familiar, frequently occurring, potentially toxic bacterial metabolites, i.e., d-lactic acid and/or ethanol. In this hypothesis we suggest that adequate probiotics can (i) prevent the increased characteristic intestinal permeability of children with atopic eczema and food allergy, (ii) can thus prevent the uptake of allergens, and (iii) finally can prevent the expression of the atopic constitution. The use of adequate probiotic lactobacilli, i.e., homolactic and/or facultatively heterolactic l-lactic acid-producing lactobacilli, reduces the intestinal amounts of the bacterial, toxic metabolites, d-lactic acid and ethanol by fermentative production of merely the non-toxic l-lactic acid from glucose. Thus, it is thought that beneficial probiotic micro-organisms promote gut barrier function and both undo and prevent unfavourable intestinal micro-ecological alterations in allergic individuals.

Adult↗