Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

OBJECTIVE: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community. METHODS: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing. RESULTS: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo. CONCLUSIONS: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

The metabolizable energy of dietary resistant maltodextrin is variable and alters fecal microbiota composition in adult men.

Resistant maltodextrin (RM) is a novel soluble, nonviscous dietary fiber. Its metabolizable energy (ME) and net energy (NE) values derived from nutrient balance studies are unknown, as is the effect of RM on fecal microbiota. A randomized, placebo-controlled, double-blind crossover study was conducted (n = 14 men) to determine the ME and NE of RM and its influence on fecal excretion of macronutrients and microbiota. Participants were assigned to a sequence consisting of 3 treatment periods [24 d each: 0 g/d RM + 50 g/d maltodextrin and 2 amounts of dietary RM (25 g/d RM + 25 g of maltodextrin/d and 50 g/d RM + 0 g/d maltodextrin)] and were provided all the foods they were to consume to maintain their body weight. After an adaptation period, excreta were collected during a 7-d period. After the collection period, 24-h energy expenditure was measured. Fluorescence in situ hybridization, quantitative polymerase chain reaction, and 454 titanium technology-based 16S rRNA sequencing were used to analyze fecal microbiota composition. Fecal amounts of energy (544, 662, 737 kJ/d), nitrogen (1.5, 1.8, 2.1 g/d), RM (0.3, 0.6, 1.2 g/d), and total carbohydrate (11.1, 14.2, 16.2 g/d) increased with increasing dose (0, 25, 50 g) of RM (P < 0.0001). Fat excretion did not differ among treatments. The ME value of RM was 8.2 and 10.4 kJ/g, and the NE value of RM was -8.2 and 2.0 kJ/g for the 25 and 50 g/d RM doses, respectively. Both doses of RM increased fecal wet weight (118, 148, 161 g/d; P < 0.0001) and fecal dry weight (26.5, 32.0, 35.8 g/d; P < 0.0001) compared with the maltodextrin placebo. Total counts of fecal bacteria increased by 12% for the 25 g/d RM dose (P = 0.17) and 18% for the 50 g/d RM dose (P = 0.019). RM intake was associated with statistically significant increases (P < 0.001) in various operational taxonomic units matching closest to ruminococcus, eubacterium, lachnospiraceae, bacteroides, holdemania, and faecalibacterium, implicating RM in their growth in the gut. Our findings provide empirical data important for food labeling regulations related to the energy value of RM and suggest that RM increases fecal bulk by enhancing the excretion of nitrogen and carbohydrate and the growth of specific microbial populations.

Adherence to guideline-directed hepatocellular carcinoma screening: A single-center US experience.

BACKGROUND: The American Association for the Study of Liver Disease recommends screening patients with cirrhosis for hepatocellular carcinoma (HCC) using imaging with or without alpha-fetoprotein every six months. Unfortunately, screening rates remain inadequate. AIM: To assess root causes of screening failure in a subspecialty hepatology clinic. METHODS: The authors identified patients with cirrhosis seen in a subspecialty hepatology clinic and determined whether they underwent appropriate screening, defined as two cross-sectional images between five and seven months apart. The authors characterized the primary driver of screening failure. Finally, other hepatologists were surveyed to determine provider perceptions of screening failure causes. RESULTS: 1034 patients were identified with an average age of 61 years and a mean MELD of 8.1 ± 3.8. Hepatitis C virus was the most common cirrhosis etiology. 489 (47%) underwent appropriate screening. No demographic or clinical differences were detected between those who underwent appropriate screening and those who did not. The most common etiologies of screening failure, in descending order, were: radiology unable to schedule timely imaging, provider did not order imaging, patient canceled follow up appointment, appointments scheduled too far apart, lost to follow up, no-show to radiology appointment, and provider canceled appointment. Hepatologists surveyed believed the most common cause of screening failure was no-show to radiology. CONCLUSION: Rates of screening were poor even in a subspecialty hepatology clinic. Screening failure was mostly due to systemic factors such as radiology availability and time between hepatology appointments rather than individual error.

Fecal lactic acid bacteria increased in adolescents randomized to whole-grain but not refined-grain foods, whereas inflammatory cytokine production decreased equally with both interventions.

The intake of whole-grain (WG) foods by adolescents is reported to be approximately one-third the recommended intake of 48 g/d. This 6-wk randomized interventional study determined the effect of replacing grains within the diet with refined-grain (RG; n = 42) or WG (n = 41) foods/d on gastrointestinal and immune health in adolescents (aged 12.7 ± 0.1 y). A variety of grain-based foods were delivered weekly to participants and their families. Participants were encouraged to eat 3 different kinds of study foods (e.g., bread, cereals, snacks)/d with goals of 0 g/d (RG) and 80 g/d (WG). Stool samples were obtained during the prebaseline and final weeks to measure bifidobacteria and lactic acid bacteria (LAB) using qPCR. Stool frequency was recorded daily. Blood was drawn at baseline and at final visits for immune markers. Across groups, total-grain intake increased by one serving. The intake of WG was similar at baseline (18 ± 3 g) between groups but increased to 60 ± 5 g in the WG group and decreased to 4 ± 1 g in the RG group. Fecal bifidobacteria increased from baseline with both interventions, but LAB increased (P < 0.05) from baseline [2.4 ± 0.2 log(10) genome equivalents (eq)] to wk 6 (3.0 ± 0.2 log(10) genome eq) in the WG group but not in the RG group (baseline: 2.9 ± 0.2 log(10) genome eq; wk 6: 3.0 ± 0.1 log(10) genome eq). There was no difference in stool frequency, serum antioxidant potential, or in vitro LPS-stimulated mononuclear cell production of inflammatory cytokines between groups. However, across both groups the number of daily stools tended to increase (P = 0.08) by 0.0034 stools/g WG or by 0.2 stools with 60 g WG, mean antioxidant potential increased by 58%, and mean production of TNF-α, IL-1ß, and IL-6 decreased by 24, 22, and 42%, respectively, between baseline and wk 6. Overall, incorporating either WG or RG foods increased serum antioxidant concentrations and decreased inflammatory cytokine production; however, WG study foods had more of an effect on aspects of gastrointestinal health.

The Effects of Kefir and Kefir Components on Immune and Metabolic Physiology in Pre-Clinical Studies: A Narrative Review.

Kefir, a fermented beverage made from kefir grains, has gained immense popularity around the world due to its potential health-promoting properties. Kefir beverages are both marketed commercially and brewed privately by individuals. Both milk and sugar solutions can be used as substrates with various additives included based on consumer preference. Fermentation occurs via microorganisms including lactic acid bacteria, acetic acid bacteria, and yeasts, which are naturally present in kefir grains. Health-promoting effects of kefir are thought to occur through immune, gastrointestinal, and metabolic regulation. Both clinical trials and mechanistic studies in cell culture and animal models have explored these effects. Studies in vitro and in animals have shown the ability of kefir and kefir components to antagonize pathogens, reduce proinflammatory cytokine production, contribute to cytotoxicity of tumor cell lines and reduce tumor burden, and improve serum glycemic and lipid profiles. However, some data from clinical trials are conflicting, and the precise mechanisms by which kefir promotes well-being are not completely defined. This review summarizes the current body of evidence in both cell culture and animal models that provide insight into the mechanisms by which kefir beverages may protect consumers from enteric infections and improve immune and metabolic health. We believe that readers will gain knowledge helpful for both developing more targeted mechanistic studies and selecting informative outcomes when designing clinical studies.

Prevalence of Postoperative Micronutrient Deficiencies in Bariatric Surgery Patients Who Use Transdermal Patches for Supplementation: A Pilot Study.

Background Patients require vitamin and mineral supplementation after bariatric surgery to prevent the development of micronutrient deficiencies. Consuming oral supplements is challenging due to gastric volume restriction. A transdermal patch dosage form may provide adequate micronutrient supplementation without pill burden. The study aims to determine the percentage of patients who have two or more nutritional deficiencies one year after surgery and to determine serum nutrient concentrations and gastrointestinal symptoms over time. Methods Patients who planned to undergo bariatric surgery and preferred transdermal patches versus oral supplements were recruited during preoperative office visits. Enrolled patients were instructed to use a transdermal multivitamin patch as per the manufacturer's instructions. Serum nutrient concentrations and Gastrointestinal Symptom Response Scale scores were determined at baseline and three months, six months, and one year after surgery. Results Ninety-two participants completed the study protocol. Twenty-five participants had a full panel of study labs one year after surgery. Among these patients, 19% had two or more micronutrient deficiencies. Vitamin D was the most common deficiency followed by vitamin B6; however, median serum concentrations of both nutrients increased over time. Vitamin B1, folate, and zinc deficiencies were also observed. There were no changes in gastrointestinal symptoms. Conclusions Additional studies, including randomized controlled trials, are required to determine if the PatchMD Multivitamin Plus patch (Pilot Rd. STE. B, Las Vegas) can provide adequate supplementation of vitamins and minerals. The patch was not associated with changes in gastrointestinal symptoms.

Undiagnosed Wilson's Disease and Fibromyalgia Masking Bowel Perforation.

Wilson's disease is a complex multi-organ disease characterized by impaired biliary excretion of copper and resulting deposition of excess copper in the liver and other organs. It has a wide range of clinical presentations, and diagnosis often requires a high degree of clinical suspicion, especially in patients with multiple other comorbidities. We present the case of a 37-year-old woman with a complex medical and psychiatric history who was admitted for chronic diarrhea, hepatic enzyme elevation, electrolyte abnormalities, hyperammonemia, and methicillin-sensitive Staphylococcus aureus bacteremia. She was eventually found to have low serum ceruloplasmin level and elevated urine copper levels. Though confirmatory liver biopsy was not performed due to bowel wall rupture and septic shock, most of her symptoms and lab abnormalities could be explained by an underlying diagnosis of Wilson's disease. We present this case primarily as a cautionary tale. This patient was not lacking in medical attention prior to this prolonged hospitalization; however, her psychiatric issues and fibromyalgia management were the predominant foci during her frequent primary care office visits and likely distracted from the patient's chronic laboratory abnormalities. More vigilant laboratory evaluation of underlying medical conditions in psychiatric patients may be warranted in order to prevent serious complications of such conditions.

A Six-Day, Lifestyle-Based Immersion Program Mitigates Cardiovascular Risk Factors and Induces Shifts in Gut Microbiota, Specifically Lachnospiraceae, Ruminococcaceae, Faecalibacterium prausnitzii: A Pilot Study.

Cardiovascular disease (CVD) prevalence remains elevated globally. We have previously shown that a one-week lifestyle "immersion program" leads to clinical improvements and sustained improvements in quality of life in moderate to high atherosclerotic CVD (ASCVD) risk individuals. In a subsequent year of this similarly modeled immersion program, we again collected markers of cardiovascular health and, additionally, evaluated intestinal microbiome composition. ASCVD risk volunteers (n = 73) completed the one-week "immersion program" involving nutrition (100% plant-based foods), stress management education, and exercise. Anthropometric measurements and CVD risk factors were compared at baseline and post intervention. A subgroup (n = 22) provided stool, which we analyzed with 16S rRNA sequencing. We assessed abundance changes within-person, correlated the abundance shifts with clinical changes, and inferred functional pathways using PICRUSt. Reductions in blood pressure, total cholesterol, and triglycerides, were observed without reduction in weight. Significant increases in butyrate producers were detected, including Lachnospiraceae and Oscillospirales. Within-person, significant shifts in relative abundance (RA) occurred, e.g., increased Lachnospiraceae (+58.8% RA, p = 0.0002), Ruminococcaceae (+82.1%, p = 0.0003), Faecalibacterium prausnitzii (+54.5%, p = 0.002), and diversification and richness. Microbiota changes significantly correlated with body mass index (BMI), blood pressure (BP), cholesterol, high-sensitivity C-reactive protein (hsCRP), glucose, and trimethylamine N-oxide (TMAO) changes. Pairwise decreases were inferred in microbial genes corresponding to cancer, metabolic disease, and amino acid metabolism. This brief lifestyle-based intervention improved lipids and BP and enhanced known butyrate producers, without significant weight loss. These results demonstrate a promising non-pharmacological preventative strategy for improving cardiovascular health.

Probiotics (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial.

Background: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2 compared with placebo would result in beneficial effects on MRQLQ scores throughout allergy season in individuals who typically experience seasonal allergies. Secondary outcomes included changes in immune markers as part of a potential mechanism for changes in MRQLQ scores.Design: In this double-blind, placebo-controlled, parallel, randomized clinical trial, 173 participants (mean ± SEM: age 27 ± 1 y) who self-identified as having seasonal allergies received either a probiotic (2 capsules/d, 1.5 billion colony-forming units/capsule) or placebo during spring allergy season for 8 wk. MRQLQ scores were collected weekly throughout the study. Fasting blood samples were taken from a subgroup (placebo, n = 37; probiotic, n = 35) at baseline and week 6 (predicted peak of pollen) to determine serum immunoglobulin (Ig) E concentrations and Treg percentages.Results: The probiotic group reported an improvement in the MRQLQ global score from baseline to pollen peak (-0.68 ± 0.13) when compared with the placebo group (-0.19 ± 0.14; P = 0.0092). Both serum total IgE and the percentage of Tregs increased from baseline to week 6, but changes were not different between groups.Conclusions: This combination probiotic improved rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies; however, the associated mechanism is still unclear. This trial was registered at clinicaltrials.gov as NCT02349711.

Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students.

BACKGROUND: Acute psychological stress induced by academic exams is associated with dysregulated gastrointestinal and immune function. OBJECTIVE: We examined whether supplementation with galactooligosaccharides reduced gastrointestinal dysfunction and the percentage of days with cold or flu in academically stressed undergraduate students. DESIGN: In a randomized, double-blind study, subjects (n = 427) received 0, 2.5, or 5.0 g galactooligosaccharides for 8 wk around the time of fall final exams. Levels of stress and cold or flu symptom intensity (SI; 0 = not experiencing to 3 = severe) were recorded daily. The SI from 9 cold or flu symptoms was summed with 1 d of cold or flu defined as a sum >6. The Gastrointestinal Symptom Response Scale was completed weekly. RESULTS: Stress was positively related to diarrhea, indigestion, and reflux syndromes and with abdominal pain, average daily cold or flu SI score, and the percentage of days with cold or flu. Gastrointestinal symptom scores for diarrhea (P = 0.0298), constipation (P = 0.0342), abdominal pain (P = 0.0058), and indigestion (P = 0.0003) syndromes were lower after galactooligosaccharide supplementation. The cold or flu SI score was affected by galactooligosaccharides and stress (P < 0.0001); 2.5 g was associated with a lower SI score across all levels of stress, but 5.0 g was protective only at lower levels of stress. The percentage of days with cold or flu was associated with galactooligosaccharides within different body mass index categories (P = 0.0002), wherein a 40% reduction in the percentage of days with cold or flu was observed in normal-weight individuals with 5.0 g galactooligosaccharides. This effect was not observed in overweight or obese individuals. CONCLUSIONS: Acute psychological stress was directly related to symptoms of gastrointestinal dysfunction and cold or flu. Galactooligosaccharide supplementation reduced these symptoms and the number of days with cold or flu. This trial was registered at clinicaltrials.gov as NCT01137760.