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Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial.
Schoemaker, MH, Hageman, JHJ, Ten Haaf, D, Hartog, A, Scholtens, PAMJ, Boekhorst, J, Nauta, A, Bos, R
Nutrients. 2022;(2)
Abstract
Constipation is a major issue for 10-20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18-59 years) received either 11 g or 5.5 g of BiotisTM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.
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2.
Association of the gut microbiota and fecal short-chain fatty acids with skeletal muscle mass and strength in children.
Chen, F, Li, Q, Chen, Y, Wei, Y, Liang, J, Song, Y, Shi, L, Wang, J, Mao, L, Zhang, B, et al
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022;(1):e22109
Abstract
We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with skeletal muscle mass and strength in healthy Chinese children aged 6-9 years. In this study, 412 children were enrolled. 16S rRNA gene sequencing was used to characterize the gut microbiota compositions. Fecal SCFAs were quantified using high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the total body lean soft tissue mass (TSM), total body fat mass (TBF), appendicular skeletal muscle mass (ASM), and appendicular fat mass (AFM). TSM/height2 (TSMI), ASM/height2 (ASMI), TSM/weight (TSMR), ASM/weight (ASMR), and the ratio of TSM/TBF and ASM/AFM were calculated. Handgrip strength (HGS) was measured using the Jamar® Plus+ Hand Dynamometer. A multiple regression analysis after adjustment for covariates and multiple test correction showed some operational taxonomic units in partial least squares models identified by Multivariate methods with Unbiased Variable selection analysis such as genera of Faecalibacterium, Lachnospira, Lachnospiraceae_ND3007_group, and Lachnospiraceae_UCG-004 were positively correlated with at least one measure of TSM, TSMI, ASM, ASMI, and ASMI Z-score (β: 0.103-0.143, pFDR : .008-.032) but negatively correlated with at least one measure of TSMR, TSM/TBF, ASMR, ASM/AFM, and ASMR Z-score (β: -0.185 to 0.124, pFDR = .008-.045). Children with higher fecal butyric acid, acetic acid, and total SCFA levels exhibited higher TSM, ASM, TSMI, ASMI, and ASMI Z-score and lower TSM/TBF, ASM/AFM, TSMR, ASMR, and ASMR Z-score. However, after additional adjustment for TBF or body mass index, only the associations for Faecalitalea and Pyramidobacter still existed. Mediation analysis suggested that total body fat significantly mediated 66.3%-95.3% of the estimated association of microbiota and SCFAs with TSM, ASM, and ASMI Z-score. Our results suggest that the associations of gut microbiota and SCFAs with skeletal muscle quality in children may largely depend upon on total body fat content.
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A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Efficacy and Safety of Lactiplantibacillus plantarum CJLP243 in Patients with Functional Diarrhea and High Fecal Calprotectin Levels.
Jung, M, Jung, S, Kim, N, Ahn, H, Yun, H, Kim, KN
Nutrients. 2022;(2)
Abstract
Micro-inflammation in the gut, assessed by fecal calprotectin (FC), is considered a component of the pathogenesis of functional diarrhea (FD). Since probiotics may suppress micro-inflammation in the intestine by competing with harmful bacteria, we hypothesized that they would reduce the ratio of loose stool symptoms and gut inflammation in patients with FD. We conducted a double-blind, placebo-controlled trial to assess the clinical and laboratory effects of Lactobacillus plantarum CJLP243 in FD patients with elevated FC levels for two months. Twenty-four patients diagnosed with FD with elevated FC levels were randomly assigned to either a probiotic group or a placebo group. After 2 months, 10 patients in the probiotic group and 12 patients in the placebo group completed the study, and FD symptoms, FC values, and intestinal flora were re-evaluated in these subjects. The percentage of subjects who had adequate FD relief (decrease in loose stool frequency) in the probiotic group was significantly increased after two months compared with the baseline. In addition, the probiotic group showed a statistically significant decrease in log-transformed FC values compared with the pre-treatment group, whereas the placebo group showed no difference before and after the intervention. Furthermore, the levels of Leuconostoc genus organisms in the gut microbiota composition in the probiotic group increased significantly after the end of the study compared with the baseline values. In this preliminary exploratory research, we found that two months of Lactiplantibacillus plantarum CJLP243 treatment resulted in FD symptom improvement, reduced FC values, and increased Leuconostoc levels, suggesting that the intake of Lactiplantibacillus plantarum was helpful in those patients. These findings need to be validated via further clinical studies.
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4.
Staging exocrine pancreatic dysfunction.
Khan, A, Vege, SS, Dudeja, V, Chari, ST
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]. 2022;(1):168-172
Abstract
Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.
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5.
Calprotectin: from biomarker to biological function.
Jukic, A, Bakiri, L, Wagner, EF, Tilg, H, Adolph, TE
Gut. 2021;(10):1978-1988
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Abstract
The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn's disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.
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Persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19: a hospital-based longitudinal study.
Joukar, F, Yaghubi Kalurazi, T, Khoshsorour, M, Taramian, S, Mahfoozi, L, Balou, HA, Jafarinezhad, A, Pourkazemi, A, Hesni, E, Asgharnezhad, M, et al
Virology journal. 2021;(1):134
Abstract
BACKGROUND The persistence of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) RNA in the body fluids of patients with the novel coronavirus disease 2019 (COVID-19) may increase the potential risk of viral transmission. There is still uncertainty on whether the recommended quarantine duration is sufficient to reduce the risk of transmission. This study aimed to investigate the persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19. METHODS In this hospital-based longitudinal study, 100 confirmed cases of COVID-19 were recruited between March 2020 and August 2020 in Guilan Province, north of Iran. Nasopharyngeal, blood, urine, and stool samples were obtained from each participant at the time of hospital admission, upon discharge, 1 week after discharge, and every 2 weeks until all samples were negative for SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) assay. A survival analysis was also performed to identify the duration of viral persistence. RESULTS The median duration of viral RNA persistence in the nasopharyngeal samples was 8 days from the first positive RT-PCR result upon admission (95% CI 6.91-9.09); the maximum duration of viral shedding was 25 days from admission. Positive blood, urine, and stool RT-PCR results were detected in 24%, 7%, and 6% of the patients, respectively. The median duration of viral persistence in the blood, urine, and stool samples was 7 days (95% CI 6.07-7.93), 6 days (95% CI 4.16-8.41), and 13 days (95% CI 6.96-19.4), respectively. Also, the maximum duration of viral persistence in the blood, urine, and stool samples was 17, 11, and 42 days from admission, respectively. CONCLUSION According to the present results, immediately after the hospitalized patients were discharged, no evidence of viral genetic materials was found. Therefore, appropriate treatments were selected for the patients at this hospital. However, we recommend further investigations on a larger sample size in multi-center and prospective randomized controlled trials (RCTs) to evaluate the effects of different drugs on the shedding of the virus through body secretions.
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Infants with cystic fibrosis have altered fecal functional capacities with potential clinical and metabolic consequences.
Eng, A, Hayden, HS, Pope, CE, Brittnacher, MJ, Vo, AT, Weiss, EJ, Hager, KR, Leung, DH, Heltshe, SL, Raftery, D, et al
BMC microbiology. 2021;(1):247
Abstract
BACKGROUND Infants with cystic fibrosis (CF) suffer from gastrointestinal (GI) complications, including pancreatic insufficiency and intestinal inflammation, which have been associated with impaired nutrition and growth. Recent evidence identified altered fecal microbiota taxonomic compositions in infants with CF relative to healthy infants that were characterized by differences in the abundances of taxa associated with GI health and nutrition. Furthermore, these taxonomic differences were more pronounced in low length infants with CF, suggesting a potential link to linear growth failure. We hypothesized that these differences would entail shifts in the microbiome's functional capacities that could contribute to inflammation and nutritional failure in infants with CF. RESULTS To test this hypothesis, we compared fecal microbial metagenomic content between healthy infants and infants with CF, supplemented with an analysis of fecal metabolomes in infants with CF. We identified notable differences in CF fecal microbial functional capacities, including metabolic and environmental response functions, compared to healthy infants that intensified during the first year of life. A machine learning-based longitudinal metagenomic age analysis of healthy and CF fecal metagenomic functional profiles further demonstrated that these differences are characterized by a CF-associated delay in the development of these functional capacities. Moreover, we found metagenomic differences in functions related to metabolism among infants with CF that were associated with diet and antibiotic exposure, and identified several taxa as potential drivers of these functional differences. An integrated metagenomic and metabolomic analysis further revealed that abundances of several fecal GI metabolites important for nutrient absorption, including three bile acids, correlated with specific microbes in infants with CF. CONCLUSIONS Our results highlight several metagenomic and metabolomic factors, including bile acids and other microbial metabolites, that may impact nutrition, growth, and GI health in infants with CF. These factors could serve as promising avenues for novel microbiome-based therapeutics to improve health outcomes in these infants.
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Current status of fecal calprotectin as a diagnostic or monitoring biomarker for cow's milk protein allergy in children: a scoping review.
Xiong, LJ, Xie, XL, Li, Y, Deng, XZ
World journal of pediatrics : WJP. 2021;(1):63-70
Abstract
BACKGROUND There are few approved biomarkers for diagnosis and monitoring of cow's milk protein allergy (CMPA), thus the oral food challenge remains to be the golden diagnostic standard. A potential biomarker is fecal calprotectin, a cytosolic protein, elevating in the presence of intestinal mucosal inflammation. We aimed to undertake a scoping review of the evidence pertaining to the current status of fecal calprotectin used for diagnosis and monitoring CMPA in children, and tried to indicate the aspects needed to be concerned in the future investigations and researches. METHODS A scoping review was performed using the literature searched from PUBMED, EMBASE, and Web of Science Databases until July 2019 on the studies about the application of fecal calprotectin as a biomarker of CMPA in children. Studies were examined according to the inclusion and exclusion criteria. Data were extracted, and a narrative synthesis was conducted to summarize and analyze. RESULTS Thirteen studies with different study design embracing 1238 children were included. The age range was from infants to adolescents. Most children with CMPA presented gastrointestinal symptoms, among which hematochezia was most common. Amount of data suggested that infants with CMPA represented elevated levels of fecal calprotectin, particularly with distinct significance in non-IgE-mediated CMPA groups. Decreases of fecal calprotectin after elimination diet were demonstrated in enrolled studies. However, no matter in the CMPA positive or negative groups, the changes of fecal calprotectin before or after challenge showed no significance. Contradictory results were generated from studies on the role of fecal calprotectin in predicting allergic disease. CONCLUSIONS Available evidence is not sufficient to confirm the utilization of fecal calprotectin both in diagnosis and monitoring of CMPA and predicting for allergic disease. More clinical and bench researches with elaborate design should be conducted and the exact cut-off values of fecal calprotectin in different groups remain to be determined.
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A Polyphenol Enriched Variety of Apple Alters Circulating Immune Cell Gene Expression and Faecal Microbiota Composition in Healthy Adults: A Randomized Controlled Trial.
Barnett, MPG, Young, W, Armstrong, K, Brewster, D, Cooney, JM, Ellett, S, Espley, RV, Laing, W, Maclean, P, McGhie, T, et al
Nutrients. 2021;(4)
Abstract
Polyphenols within fruits and vegetables may contribute to health benefits due to their consumption, with the anthocyanin sub-set also adding colour. The Lemonade™ apple variety has green skin and white flesh, with low anthocyanin content, while some apple varieties have high anthocyanin content in both the skin and flesh. Effects of red compared with white-fleshed apples were studied in healthy human subjects in a randomized, placebo-controlled, cross-over intervention trial. Twenty-five healthy subjects consumed dried daily portions of the red-fleshed or placebo (white-fleshed) apple for two weeks, followed by one-week washout and further two-week crossover period. During the study, volunteers provided faecal samples for microbiota composition analysis and blood samples for peripheral blood mononuclear cell (PBMC) gene expression analysis. Subtle differences were observed in the faecal microbiota of subjects that were fed the different apples, with significant (p < 0.05) reductions in relative abundances of Streptococcus, Ruminococcus, Blautia, and Roseburia, and increased relative abundances of Sutterella, Butyricicoccus, and Lactobacillus in subjects after consuming the red apple. Changes in PBMC gene expression showed 18 mRNA transcripts were differentially expressed between the two groups, of which 16 were immunoglobulin related genes. Pathway analysis showed that these genes had roles in pathways such as immunoglobulin production, B cell-mediated immunity, complement activation, and phagocytosis. In conclusion, this study shows that anthocyanin-rich apples may influence immune function compared to control apples, with changes potentially associated with differences in the faecal microbiota.
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Maternal fecal microbiome predicts gestational age, birth weight and neonatal growth in rural Zimbabwe.
Gough, EK, Edens, TJ, Geum, HM, Baharmand, I, Gill, SK, Robertson, RC, Mutasa, K, Ntozini, R, Smith, LE, Chasekwa, B, et al
EBioMedicine. 2021;:103421
Abstract
BACKGROUND Preterm birth and low birth weight (LBW) affect one in ten and one in seven livebirths, respectively, primarily in low-income and middle-income countries (LMIC) and are major predictors of poor child health outcomes. However, both have been recalcitrant to public health intervention. The maternal intestinal microbiome may undergo substantial changes during pregnancy and may influence fetal and neonatal health in LMIC populations. METHODS Within a subgroup of 207 mothers and infants enrolled in the SHINE trial in rural Zimbabwe, we performed shotgun metagenomics on 351 fecal specimens provided during pregnancy and at 1-month post-partum to investigate the relationship between the pregnancy gut microbiome and infant gestational age, birth weight, 1-month length-, and weight-for-age z-scores using extreme gradient boosting machines. FINDINGS Pregnancy gut microbiome taxa and metabolic functions predicted birth weight and WAZ at 1 month more accurately than gestational age and LAZ. Blastoscystis sp, Brachyspira sp and Treponeme carriage were high compared to Western populations. Resistant starch-degraders were important predictors of birth outcomes. Microbiome capacity for environmental sensing, vitamin B metabolism, and signalling predicted increased infant birth weight and neonatal growth; while functions involved in biofilm formation in response to nutrient starvation predicted reduced birth weight and growth. INTERPRETATION The pregnancy gut microbiome in rural Zimbabwe is characterized by resistant starch-degraders and may be an important metabolic target to improve birth weight. FUNDING Bill and Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, and UNICEF.