Three probiotic strains exert different effects on plasma bile acid profiles in healthy obese adults: randomised, double-blind placebo-controlled crossover study.

Microbial metabolism in the gut may alter human bile acid metabolism in a way that beneficially affects lipid homeostasis and therefore cardiovascular disease risk. Deconjugation of bile acids by microbes is thought to be key to this mechanism but has yet to be characterised in blood and stool while observing lipid markers. The aim of this study was to determine the effect of 3 different probiotic strains on plasma and stool bile acids in the context of lipid and glucose metabolism. In this 18-week, randomised, double-blind crossover study, healthy adults (53±8 years) with a high waist circumference underwent a 1-week pre-baseline period and were then randomised to receive 1 capsule/day of Bacillus subtilis R0179 (2.5×109 cfu/capsule; n=39), Lactobacillus plantarum HA-119 (5×109 cfu/capsule; n=38), Bifidobacterium animalis subsp. lactis B94 (5×109 cfu/capsule; n=37) or placebo for 6 weeks. Following a 3-week washout and second pre-baseline week, participants were crossed to the other intervention for 6 weeks followed by a 1-week post-intervention period. Blood and stool samples were collected at the beginning and end of each intervention to measure bile acids, serum lipid profiles, and glucose and insulin levels. Data from the placebo intervention were combined for all participants for analyses. In obese participants, the difference (final-baseline) in the sum of deconjugated plasma bile acids was greater with consumption of B. subtilis (691±378 nmol/l, P=0.01) and B. lactis (380±165 nmol/l, P=0.04) than with placebo (98±176 nmol/l, n=57). No significant differences were observed for any probiotics for stool bile acids, serum lipids, blood glucose or insulin. These data suggest that B. subtilis and B. lactis had no effect on glucose metabolism or serum cholesterol but increased deconjugated plasma bile acids in obese individuals. Additional studies should be conducted to confirm these findings and explore potential mechanisms. This trial was registered at clinicaltrials.gov as NCT01879098.

Bifidobacterium bifidum R0071 decreases stress-associated diarrhoea-related symptoms and self-reported stress: a secondary analysis of a randomised trial.

Psychological stress is associated with gastrointestinal (GI) distress. This secondary analysis from a randomised, double-blind, placebo-controlled study examined whether three different probiotics could normalise self-reported stress-associated GI discomfort and reduce overall self-reported stress. Undergraduate students (n=581) received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071, or placebo. Participants self-reported 2 outcomes for a 6-week period, which included final academic exams: daily level of stress (0=no stress to 10=extremely stressed) and weekly three diarrhoea-related symptoms (DS, 1=no discomfort to 7=severe discomfort) using the GI Symptom Rating Scale. Self-reported stress was positively related to DS (P=0.0068). Mean DS scores were lower with B. bifidum versus placebo at week 2 at the average level of stress and the average body mass index (BMI). DS scores were lower with B. bifidum at week 5 versus week 0 and 1 and with B. infantis R0033 at week 6 versus week 0. DS scores were higher when antibiotics were used in the prior week with placebo (P=0.0092). DS were not different with or without antibiotic use with the probiotics. Only B. bifidum had an effect on self-reported stress scores (P=0.0086). The self-reported stress score was also dependent on hours of sleep per day where it decreased by 0.13 for each additional hour of sleep. During a stressful period, B. bifidum R0071 decreases DS and self-reported stress scores. This trial was registered at clinicaltrials.gov as NCT01709825.

Usefulness of the MNA in the long-term and acute-care settings within the United States.

The Mini Nutritional Assessment (MNA) is a tool that was developed for use with elders to provide rapid assessment of nutritional risk. Although this screening tool has been validated and frequently used in longterm and acute-care settings in Europe, the MNA has not been used extensively within the United States. The MNA may need to be validated for use within U.S. nursing and acute-care facilities because validity may be affected by the acuity of illness, the use of aggressive nutrition support, which makes the scoring of the MNA difficult, and the age of patients admitted for care (acute care). Additionally, in most long-term care settings, a specific screening tool (Minimum Data Set) is already required to assess resident function including nutritional risk. The MNA may be more useful in an assisted living facility, where nutrition screening and assessment tools are not currently in place, yet maintenance of functional status is important to prevent transfer to a nursing facility.

Nutrient recommendations for wound healing.

Current knowledge about nutritional therapy and wound healing in humans is presented in this review. Recommendations for vitamins A, C, and E, zinc, protein, arginine, and water, as well as their roles in wound healing, are discussed. Where available, scientific data supporting each recommendation are included, along with assessment methods. A brief overview of the wound healing process is presented.

Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers.

BACKGROUND: Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. METHODS: Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. RESULTS: Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. CONCLUSIONS: Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.

Arginine enhances In vivo immune responses in young, adult and aged mice.

Arginine supplementation enhances in vitro lymphocyte proliferation in healthy adult humans and in rodent models. Studies examining the effect of arginine supplementation on in vivo immune responses are lacking. The purpose of this study was to determine whether arginine supplementation could enhance in vivo immune responses in adult mice and reverse known age-associated alterations in immune function of young and aged mice. Mice (1, 10 and 33 mo old) were fed a 2% arginine or an isonitrogenous diet for 2 wk. Delayed-type hypersensitivity to 2,4-dinitrofluorobenzene-challenged ears and changes in popliteal lymph node weights to injected sheep red blood cells were measured. The mean percentage of increase in ear thickness in challenged vs. unchallenged ears was 27, 35 and 24% with arginine supplementation and 7, 12 and 0% with the isonitrogenous diet in the 1-, 10- and 33-mo-old mice, respectively (P

Arrested maturation of granulocytes in copper deficient mice.

The objective of this study was to examine the role of copper in neutrophil development and function. Mice were made copper deficient by feeding dams a diet containing 1.05 microg copper starting at parturition. Control mice were fed the same diet containing 6 microg copper. The pups were weaned to the diet and killed when they were 5-6 wk old. Peripheral blood cell counts, margination and cell maturity were measured. The response to an intraperitoneal injection of lipopolysaccharide (LPS) was also determined. Copper deficiency resulted in twice as many neutrophils and fewer than half the number of lymphocytes. Half as many cells in copper-deficient mice expressed Ly-6G, a granulocytic marker of cell maturity. In addition, copper-deficient cells expressed only half the amount of Ly-6G per cell than was expressed by copper-adequate cells. This suggested that the cells were younger, or arrested in their maturation as a result of copper deficiency. An arrest of maturation has been proposed as the cause of neutropenia in human copper deficiency. Injection of LPS in copper-adequate mice resulted in twice as many Ly-6G-expressing cells in the periphery. LPS injection into copper-deficient mice resulted in a severe leukopenia but did not influence Ly-6G expression any more than did copper deficiency alone. LPS treatment caused an increase in myeloperoxidase activity associated with the lungs of copper-deficient mice. The results suggest that although the neutrophils of copper-deficient mice are immature, they can be sequestered by the lung when stimulated to do so.

Differential effect on polyamine metabolism in mitogen- and superantigen-activated human T-cells.

Polyamines are important for regulation of lymphocyte differentiation and proliferation. Mitogens induce synthesis of ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine biosynthesis. Since mitogens stimulate T-cells by non-physiological routes, the role of polyamine metabolism in T-cell receptor (TCR)-mediated T-cell activation has not been adequately evaluated. The effect of phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) on T-cell ODC and polyamine synthesis was compared. ODC activity was 6-11-fold higher in PHA compared to SEB stimulated T-cells. These differences were not attributed to differences in the magnitude of T-cell proliferation. Kinetics of ODC and polyamine synthesis were also different in PHA- and SEB-stimulated T-cells. In PHA-stimulated cells ODC levels and the induction of putrescine and spermidine synthesis peaked 6 h prior to peak IL-2 production, while in SEB-stimulated cells, ODC levels and polyamine synthesis peaked 6-12 h after IL-2 production. Differences in the temporal relationship between IL-2 production and polyamine induction in mitogen- versus superantigen-stimulated cells may account for the significant inhibition of the proliferative response by alpha-difluoromethylornithine following PHA but not SEB stimulation. Polyamine metabolism is regulated differently in T-cells stimulated via TCR engagement than with polyclonal mitogens.

Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue.

Changes in mucosal defense have been implicated as important factors affecting infections complications in critically ill patients. To study the effects of nutrient administration on gut-associated lymphatic tissue (GALT), ICR mice were randomized to receive chow plus intravenous saline, intravenous feeding of a total parenteral nutrition (TPN) solution, or enteral feeding of the same TPN solution. In a second series of experiments, a more complex enteral diet (Nutren) was compared with chow feeding and enteral TPN. After 5 days of feeding with experimental diets, lymphocytes were harvested from the mesenteric lymph nodes (MLNs), Peyer's patches (PPs), lamina propria (LP) cells, and intraepithelial (IE) spaces of the small intestine to determine cell yields and phenotypes. Small intestinal washings, gallbladder contents, and sera were collected and analyzed for immunoglobulin A (IgA) levels. In both series of experiments, there were no significant changes within the MLNs. There were significant decreases in total cell yields from the PPs, IE spaces, and LP in animals fed with TPN solution, either enterally or parenterally, as compared with chow-fed mice. Total T cells were decreased in both TPN-fed groups in the PPs and LP, whereas total B cells were decreased in the PP, IE, and LP populations. Total cell numbers remained normal in the Nutrenfed group, except for a decrease in LP T cells. CD4+ LP cells decreased significantly with a reduction in the CD4/CD8 ratio in mice fed TPN solution either intravenously or enterally, whereas IgA recovery from small intestinal washings was significantly decreased in the same groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased intestinal permeability following blunt and penetrating trauma.

OBJECTIVES: To determine changes in the absorption of lactulose and mannitol in patients undergoing laparotomy following blunt or penetrating trauma and to correlate any changes in permeability with the severity of injury. DESIGN: Nonrandomized study within patient control. PATIENTS: Consecutive patients admitted to the trauma unit following blunt or penetrating trauma with intra-abdominal injuries warranting emergent celiotomy and jejunal access. INTERVENTIONS: Intestinal permeability was measured in 18 patients within 48 hrs post-trauma by the bolus infusion into the jejunum of nonmetabolized probe molecules, lactulose (molecular weight of 342) and mannitol (molecular weight of 182). Because several patients did not tolerate the bolus infusion, a 3-hr continuous infusion of the probe molecules was used in the last eight patients entered into the study. Intestinal permeability was reassessed before discharge or on days 10 to 12. MEASUREMENTS AND MAIN RESULTS: There was a decrease in urinary lactulose excretion and the lactulose/mannitol ratio between the initial posttrauma measurement and the follow-up permeability measurement using both the bolus infusion (lactulose: initial 0.13 +/- 0.032 vs. follow-up 0.047 +/- 0.012 mmol/6 hrs, p < or = .05; lactulose/mannitol: initial 0.067 +/- 0.012 vs. follow-up 0.044 +/- 0.012, p = .11) and the continuous infusion (lactulose: initial 0.044 +/- 0.013 vs. follow-up 0.014 +/- 0.002 mmol/2 hrs, p < or = .05; lactulose/mannitol: initial 0.055 +/- 0.020 vs. follow-up 0.015 +/- 0.007, p < or = .05). Urine excretion of mannitol was not significantly different between posttrauma and follow-up measurements of intestinal permeability, regardless of the technique used to infuse the lactulose and mannitol. Although the decrease in lactulose and the lactulose/mannitol ratio was significant, only one third of the patients had dramatically increased permeability at the initial measure. Abdominal Trauma Index and Injury Severity Score did not correlate with urinary lactulose excretion or the lactulose/mannitol ratio. Patient tolerance of jejunal administration of lactulose and mannitol was better, using a 3-hr continuous infusion of a dilute solution compared with bolus infusion. CONCLUSIONS: Intestinal permeability is increased in the first 48 hrs posttrauma and decreases with recovery. Although one third of the patients had highly increased lactulose/mannitol ratios posttrauma, severity of injury, assessed by common scoring techniques, did not correlate with the degree of permeability. Tolerance to jejunal administration of lactulose and mannitol is improved with a slow infusion of a dilute solution over a 3-hr period compared with bolus administration.

Fasting-induced reduction of intestinal reperfusion injury.

BACKGROUND: Fasting is associated with significant structural, functional, and metabolic alterations in the intestinal mucosa. Before abdominal surgery, patients are usually fasted the night before surgery or for a longer period of time if chronic illness is present. The splanchnic organs may experience varying degrees of ischemia/reperfusion as blood vessels are occluded during the various manipulations. METHODS: To study whether fasting alters intestinal reperfusion injury, rats were fasted for 0 to 2 days, and the mesenteric artery was occluded for 30 minutes and then reperfused for 1 hour. Mucosal atrophy was quantitated by measuring jejunal villus height and crypt depth, and mucosal injury was quantitated by measuring jejunal villus width to villus height and mucosal integrity. To determine whether any effect of fasting on reperfusion injury was due to the absence of luminal nutrients or to a systemic nutrient deficiency, rats were fed parenterally for 7 days before ischemia/reperfusion. RESULTS: A 1-day fast produced significant mucosal atrophy. Reperfusion in the 0-day and 1-day fasted animals produced mucosal injury and additional mucosal atrophy. After a 2-day fast, there was no mucosal injury or mucosal atrophy other than that produced by fasting alone. Parenteral feeding before ischemia/reperfusion did not prevent ischemia/reperfusion induced mucosal atrophy and injury. CONCLUSIONS: The protective effect of a 2-day fast before intestinal ischemia/reperfusion cannot be attributed to the physical and chemical absence of food within the intestinal lumen.

Characterization of distinct forms of methionine adenosyltransferase in nucleated, and mature human erythrocytes and erythroleukemic cells.

Two peaks of methionine adenosyltransferase (MAT) activity from human erythrocytes were partially purified on a DEAE-cellulose column. Using anti-MAT antibodies, a 60 kDa form of MAT, referred to as rho was identified in peak I. Although rho represented the major MAT protein in crude erythrocyte extracts, the enzyme was very labile and accounted for only 6% of the total MAT activity. Peak II enzyme was stable, and consisted of the previously described catalytic alpha (53 kDa) subunit and the beta subunit (38 kDa), both of which are found in activated human lymphocytes and leukemic cells of lymphoid origin. Mature normal and polycythemic erythrocytes contained predominantly rho as the major MAT protein, while nucleated erythrocytes and reticulocytes contained predominantly the lambda (68 kDa), the major form found in resting human lymphocytes. Human erythroleukemic cells (HEL 92.1.7) contained the alpha, alpha' and beta subunits of MAT, and in this regard was indistinguishable from MAT found in activated lymphocytes and leukemic cells of lymphoid origin (Jurkat). Since rho was generated during the incubation of extracts from resting lymphocytes, which contain predominantly lambda, in the absence of protease inhibitors; the rho form of MAT appears to be derived from the lambda form by proteolytic cleavage. The data indicate that distinct forms of MAT are present at different stages of erythrocyte maturation and reveal the presence of a new form of MAT with reduced activity compared to previously described forms.

Glutamine prevents parenteral nutrition-induced increases in intestinal permeability.

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. This study evaluated changes in rat jejunal permeability and histology after total parenteral nutrition (TPN) or TPN supplemented with glutamine. Lactulose and mannitol were used to measure jejunal permeability, and fixed stained histologic specimens were used to measure mucosal dimensions. After the insertion of central venous catheters, 18 male rats were randomly divided into three groups: CHOW, saline infusion with a standard laboratory rat diet ad libitum; TPN; and GLN, 2% L-glutamine-supplemented TPN. The TPN and GLN groups received isocaloric, isovolumic, and isonitrogenous feedings. After 7 days of infusion, a laparotomy was performed, and lactulose and mannitol were instilled into the lumen of a 25-cm ligated segment of jejunum. Urine was collected for 5 hours and assayed for lactulose, mannitol, and creatinine. The jejunum was harvested, and wet weight, villus height, mucosal thickness, and villus width were measured. Intestinal permeability to lactulose and the lactulose to mannitol ratio significantly increased after TPN compared with CHOW, and these effects were prevented with the addition of glutamine to the TPN solution. Jejunal villus height and mucosal thickness significantly decreased following TPN but were not significantly different from CHOW when glutamine was added to the TPN solution. These data suggest that TPN was associated with increased jejunal permeability and that glutamine, when added to the TPN solution, prevented this effect. In addition, glutamine reduced TPN-associated atrophy of the jejunum.

Immunologic structure and function of the gastrointestinal tract.

Host defenses within the gastrointestinal tract exclude bacteria and other intraluminal substances, which if released into the systemic circulation, would be toxic to the body. This is accomplished via complex interactions between these external pathogens and local immune responses and nonimmunologic processes. In addition to the mechanical and chemical barriers of the nonimmunologic defense system within the gastrointestinal tract, there is an effective immunologic barrier composed of aggregated and nonaggregated lymphoid cells. Gut-associated lymphoid tissue protects the intestinal mucosa from invading pathogens by intricate pathways of antigen processing. Gut-associated lymphoid tissue also transfers protection to other secretory sites within the body through the common mucosal immune system. The integrity of both the immunologic and nonimmunologic barriers may be affected by any number of pathologic insults as well as by nutritional influences. This article reviews the structural and functional characteristics of this complex and critically important host defense system. Specific nutrient requirements of the immunologic processes are discussed.