Consensus statements from the Workshop 'Probiotics and Health: Scientific Evidence' / Declaraciones consensuadas del Workshop: “Probióticos y Salud: Evidencia Científica”

This report shows the level of scientific consensus on definition, characteristics and health benefits of probiotics. The content of the report has derived from the scientific meeting: Workshop on Probiotics and Health. Scientific evidence, that congregated several Spanish experts, including gastroenterologists, microbiologists, nutritionists, immunologists and food technologists, among others, who have agreed with the statements shown in this document. Each statement has been sustained with the most relevant scientific aspects that were discussed during the Workshop and the following evaluation of there port by all experts who approved and signed it (AU)

En este documento se muestra una base de consenso entorno a la definición, características y propiedades beneficiosas de los probióticos. El contenido fue generado a partir de la reunión científica Workshop Probióticos y Salud. Evidencia Científica, que agrupó a una variedad de expertos españoles gastroenterólogos, microbiólogos, nutricionistas, inmunólogos y tecnólogos de alimentos, entre otros, que se han adherido en su mayoría a las sentencias que constituyen este documento. Para cada sentencia se establecen las aspectos científicos más relevantes que la respaldan y que son consecuencia del acuerdo al que se ha llegado tras el debate surgido en la reunión y la evaluación posterior del contenido por todos los expertos que han firmado este documento (AU)

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin.

BACKGROUND: Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. OBJECTIVE: To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. DESIGN: Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g/day) and randomly allocated to receive either oligofructose-enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. RESULTS: Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 +/- 659 microg/g; day 7: 1033 +/- 393 microg/g, P < 0.05) but not in the placebo group (day 0: 5834 +/- 1563 microg/g; day 7: 4084 +/- 1395 microg/g, n.s.). Changes in faecal concentration of human DNA were not significant. CONCLUSION: In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.

Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.

OBJECTIVES: Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis. METHODS: Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode. RESULTS: Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect. CONCLUSIONS: Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.

Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis.

BACKGROUND & AIMS: Polyunsaturated phosphatidylcholine stimulates collagen breakdown in experimental models of liver cirrhosis. Bowel strictures are characterized by excess deposition of collagen in the intestinal wall. The aim of this study was to investigate the effect of polyunsaturated phosphatidylcholine in the prevention of bowel strictures. METHODS: Colitis was induced by trinitrobenzenesulfonic acid. On day 21, the presence of strictures was assessed in control rats, rats with colitis, and phosphatidylcholine-fed (100 mg/day) rats with colitis. Furthermore, serum transforming growth factor beta1, collagen deposition, and collagenase activity in colonic tissue were measured in all groups. RESULTS: None of the control rats but 12 of 16 rats with colitis developed colonic strictures. In contrast, only 2 of 15 phosphatidylcholine-fed rats with colitis showed strictures. Collagen content was much higher in rats with colitis than in phosphatidylcholine-fed rats with colitis and control rats. Phosphatidylcholine-fed rats showed significantly higher collagenase activity in colonic tissue than rats with colitis and control rats. In an ancillary study, free linoleic acid-fed rats showed no differences when compared with rats with colitis. Stimulation of transforming growth factor beta1 was similar in all rats with colitis. CONCLUSIONS: Oral supplementation with polyunsaturated phosphatidylcholine prevents the accumulation of collagen in inflamed intestinal tissue and the formation of strictures. This effect is associated with an enhanced collagen catabolism.

Regulation of gall bladder motility by the arginine-nitric oxide pathway in guinea pigs.

Nitric oxide (NO) synthesised from L-arginine is an intercellular messenger in various biological actions including endothelial dependent relaxation and inhibition of platelet aggregation. This study explored the role of the L-arginine-NO pathway in the regulation of gall bladder motility. Intraluminal gall bladder pressure was recorded in anaesthetised guinea pigs in response to cholecystokinin or bethanechol before and after treatment with specific NO synthase inhibitors (NG-nitro-L-arginine, NG-nitro-L-arginine methyl ester, or NG-monomethyl-L-arginine), or with an NO donor (sodium nitroprusside). Baseline gall bladder pressure significantly increased after treatment with the NO synthase inhibitors. Responses to cholecystokinin (0.025-1.25 nmol/kg) were significantly enhanced after treatment with NG-nitro-L-arginine methyl ester and lasted two to threefold longer than in control experiments. The effect of the inhibitor both on resting pressure and on cholecystokinin induced changes was reversed by L-arginine but not by D-arginine. Pretreatment with the inhibitors also induced a significant enhancement of the response to bethanechol. On the other hand, sodium nitroprusside abolished the response to low dose cholecystokinin and reduced the response to a high dose by about 80%. In vitro experiments with isolated gall bladder strips showed a significant enhancement of the contractile response to cholecystokinin or bethanechol after preincubation with the NO synthase inhibitor. Calcium dependent activity of NO synthase was detected in fresh homogenates from gall bladder tissue and incubation with endotoxin induced considerable calcium independent activity. These findings support the existence of a key L-arginine-nitric oxide pathway regulating gall bladder contraction.

Dietary manipulation in experimental inflammatory bowel disease.

Eicosanoids are major mediators of defensive and inflammatory processes of the gut mucosa. The activity of the eicosanoid system is modulated by neural and hormonal pathways, but local factors acting within the gastrointestinal lumen may also be involved. We have studied the influence of dietary fatty acids on eicosanoid synthesis by the gastrointestinal mucosa. Since omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower or cod liver oil as sources of omega-6 or omega-3 fatty acids, respectively. Rats fed with the cod-liver-oil-supplemented diet for four weeks showed high omega-3 and low omega-6 plasma fatty acid levels compared to rats fed with the sunflower oil diet. Synthesis of arachidonic-acid-derived eicosanoids (6-keto-PGF1 alpha, PGE2, TXB2, LTB4, and LTC4) by gastric and intestinal mucosa was found to be lower in the cod liver group as compared to the sunflower group. However, significant generation of eicosapentaenoic-acid-derived eicosanoids (PGE3 and LTC5) was observed only in the cod liver group. We used the (trinitrobenzenesulphonic acid) TNBS model of inflammatory colitis to test the effect of the dietary fat on the development of inflammatory lesions of the bowel. A single intracolonic instillation of the hapten TNBS dissolved in 10% ethanol induces chronic granulomatous lesions of the colonic mucosa that persist for up to 8 weeks. Luminal release of eicosanoid mediators, as measured by intracolonic dialysis, was lower in the cod liver group than in the sunflower group, particularly during the chronic stage of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis.

Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity.