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Probiotics Partly Suppress the Impact of Sugar Stress on the Oral Microbiota-A Randomized, Double-Blinded, Placebo-Controlled Trial.
Lundtorp Olsen, C, Massarenti, L, Vendius, VFD, Gürsoy, UK, Van Splunter, A, Bikker, FJ, Gürsoy, M, Damgaard, C, Markvart, M, Belstrøm, D
Nutrients. 2023;15(22)
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In oral health, the oral microbiota thrives with the human host, whereas dysbiotic compositional changes are associated with development of oral diseases. Free sugars constitute the most important dietary risk factor for the development of dental caries, with a dose-response relationship. The aim of this study was to determine if consumption of probiotic lozenges containing an equal mix of L. rhamnosus PB01 DSM14870 and L. curvatus EB10 DSM32307 and xylitol could counteract oral dysbiosis in the supragingival microbiota. This study was a quadruple-blinded (participant, care provider, investigator, outcome assessor), randomised, placebo-controlled, clinical trial. This study recruited eighty orally and systemically healthy individuals aged 19–31 years. Participants were randomly assigned to the placebo or intervention group. Results showed that probiotics partly counteract sugar-mediated loss of diversity in the supragingival microbiota, which was observed in the placebo group. Consequently, from a microbiological point of view, the probiotic supplement augmented resilience of the supragingival microbiota in the resolution period after sugar stress. Authors concluded that probiotics affect the composition of the supragingival microbiota during short-term sugar stress in healthy individuals.
Abstract
The aim was to test if probiotics counteract oral dysbiosis during 14 days of sugar stress and subsequently help restore oral homeostasis. Eighty healthy individuals received either probiotics (n = 40) or placebo lozenges (n = 40) for 28 days and rinsed with a 10% sucrose solution 6-8 times during the initial 14 days of the trial. Saliva and supragingival samples were collected at baseline, day 14, and day 28. Saliva samples were analyzed for levels of pro-inflammatory cytokines, albumin, and salivary enzyme activity. The supragingival microbiota was characterized according to the Human Oral Microbiome Database. After 14 days of sugar stress, the relative abundance of Porphyromonas species was significantly higher (p = 0.03) and remained significantly elevated at day 28 in the probiotic group compared to the placebo group (p = 0.004). At day 28, the relative abundance of Kingella species was significantly higher in the probiotic group (p = 0.03). Streptococcus gordinii and Neisseria elongata were associated with the probiotic group on day 28, while Streptococcus sobrinus was associated with the placebo group on day 14 and day 28. On day 28, the salivary albumin level was significantly lower in the probiotic group. The present study demonstrates a potential stabilizing effect on the supragingival microbiota mediated by consumption of probiotics during short-term sugar stress.
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Effect of Lacticaseibacillus paracasei N1115 on Immunomodulatory and Gut Microbial Composition in Young Children: A Randomized, Placebo-Controlled Study.
Li, P, Ren, Z, Zhou, J, Zhao, A, Wang, S, Xun, Y, Jiang, H, Wang, P, Yuan, Q, Zhang, Y
Nutrients. 2023;15(8)
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Cesarean section (C-section) is one of the most common obstetrical procedures, and China is among the countries with the highest C-section rates in the world. Lactobacillus is one of the well-known and most studied probiotics and has a broad distribution in the human oral cavity, genitourinary tract, gastrointestinal tract, and milk. The aim of this study was to investigate the efficacy of Lp N1115 as a probiotic on immunomodulatory and gut microbial composition in Chinese infants and toddlers born by C-section. This study was a single-centre, randomised, triple-blind placebo-controlled trial. Healthy infants born by C-section were recruited at the age of 6–24 months and divided into two age groups: 6–12 months and 13–24 months. Infants and toddlers were randomly assigned to either the experimental group (Lp N1115 group) or the placebo-control group. Results showed that Lp N1115 can help maintain the intestinal pH of infants aged 6–24 months after C-section, improve immune function, and promote the proliferation of Lactobacillus. Furthermore, Lp N1115 could increase faecal secreted immunoglobulin A levels and, to some extent, reduce cortisol levels in infants and children. Authors conclude that the beneficial effects of Lp N1115 on gut development were more obvious in 6–12-month-old infants.
Abstract
Lactobacillus paracasei N1115 (Lp N1115) was isolated from fermented milk products. The administration of Lp N1115 is safe and well tolerated in Chinese children, but its effectiveness among young Chinese children is still unclear. To investigate the efficacy of Lp N1115 as a probiotic to enhance gut development in Chinese infants and toddlers born by cesarean section, 109 healthy and cesarean-delivered infants aged 6-24 months were recruited for a 12-week randomized, placebo-controlled trial, with 101 finally completing the study. Saliva and stool samples were collected and detected at weeks 0, 4, 8, and 12 of the intervention. Statistical analyses were performed by using a per-protocol (PP) approach. After 12 weeks of intervention, the fecal pH in the control group increased (p = 0.003), while the fecal pH in the experimental group did not change. Salivary cortisol decreased from baseline in the experimental group (p = 0.023), while the control group showed little change. In addition, Lp N1115 increased the fecal sIgA content of infants aged 6-12 months (p = 0.044) but had no obvious effect on fecal calprotectin and saliva sIgA. At week 4, the increase in Lactobacillus relative to baseline was higher in the experimental group than in the control group (p = 0.019). Further analysis showed a trend toward a higher detection rate of Lactobacillus in the experimental group than in the control group (p = 0.039). In conclusion, Lp N1115 was able to enhance the content of Lactobacillus and maintain fecal pH levels. Its beneficial effects on gut development were more obvious in 6-12-month-old infants.
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The Effect of Dietary Advice Aimed at Increasing Protein Intake on Oral Health and Oral Microbiota in Older Adults: A Randomized Controlled Trial.
Fluitman, KS, van den Broek, T, Reinders, I, Wijnhoven, HAH, Nieuwdorp, M, Visser, M, IJzerman, RG, Keijser, BJF
Nutrients. 2023;15(21)
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It is well-established that nutrition and oral health are closely related. This relationship is especially evident in older adults, in whom both oral health and nutritional status are often compromised. The aim of this study was to evaluate the effect of the intervention on oral health and the oral microbiota composition in community-dwelling older adults. This study was part of the 6-month, multicentre, randomised controlled PROMISS trial which randomly assigned participants into 3 groups. For this study a total of 90 participants were included, 47 from the high protein group and 43 from the control group. Results showed that increasing protein intake from an average of 0.8 g/kg adjusted body weight/day (aBW/d) to 1.2 g/kg aBW/d does not affect self-reported oral health status in older adults. Moreover, whereas moderate effects were observed on the overall microbiota composition based on alpha- and beta-diversity measures, no individual bacterial taxa were found to be specifically affected. Authors concluded that dietary advice aimed at increasing protein intake to at least 1.2 g/kg aBW/d in older adults with habitual low protein intake did not significantly improve self-reported oral health.
Abstract
Nutrition and oral health are closely related, especially in older adults in whom poor nutrition may lead to oral microbial perturbations, exacerbating poor oral health. In a 6-month randomized controlled trial, we evaluated the effects on oral microbiota and on oral health of dietary advice aimed at increasing protein intake to ≥1.2 g/kg adjusted body weight/day (g/kg aBW/d) in community-dwelling older adults with low habitual protein intake (<1.0 g/kg aBW/d). Food intake was measured via 24 h dietary recalls, oral health was measured via questionnaires, and oral microbial composition was assessed via the 16S rRNA sequencing of tongue swabs. Mean baseline protein intake was 0.8 g/kg aBW/day in both groups. In the high protein group (n = 47), participants increased their protein intake to mean 1.2 g/kg aBW/day at the 6-month follow-up. Protein intake in the control group (n = 43) remained at 0.9 g/kg a BW/day. The intervention did not affect self-reported oral health. While it caused moderate shifts in oral microbiota alpha- and beta-diversity measures, abundances of individual bacterial taxa were not affected. In conclusion, our intervention did not affect self-reported oral health within a period of 6 months, nor did it substantially affect the tongue microbiota composition.
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Effects of 24-week prebiotic intervention on self-reported upper respiratory symptoms, gastrointestinal symptoms, and markers of immunity in elite rugby union players.
Parker, C, Hunter, KA, Johnson, MA, Sharpe, GR, Gibson, GR, Walton, GE, Poveda, C, Cousins, B, Williams, NC
European journal of sport science. 2023;23(11):2232-2239
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Elite rugby union players follow physiologically and psychologically demanding training schedules, with frequent competitive matches, limited recovery time, and regular international travel. Collectively, these stressors may impair immunity and increase the risk of acute upper respiratory symptoms (URS) (e.g. cough, sneezing, sore throat & nasal congestion) and gastrointestinal symptoms (GIS) (e.g. bloating, belching, flatulence, nausea and diarrhoea). The aim of this study was to assess the effects of a 168-day Bimuno-galactooligosaccharides (B-GOS) supplementation on the severity, duration and incidence of URS and GIS, salivary immunoglobulin A (sIgA), and plasma concentrations of C-reactive protein and TNF-α in elite rugby union players during a competitive season. This study was a randomised, double-blind, placebo-controlled trial over 168-days during a regular rugby union season. Participants were matched into pairs based on body mass and playing position before randomly being allocated an intervention. Results showed that daily supplementation with the dietary prebiotic B-GOS reduced the duration of URS and incidence of GI symptoms. Furthermore, B-GOS increased sIgA secretion rate at 168 days when compared to the placebo group. Authors concluded that prebiotic use may have the potential to modulate immune function and reduce illness, which may improve an athlete’s availability to train and compete.
Abstract
OBJECTIVES Elite rugby union players face numerous physiological and psychological stressors which can increase upper respiratory and gastrointestinal illness risk, and in turn can compromise training and competitive performance. This study aimed to investigate the effect of daily prebiotic supplementation on upper respiratory symptoms, gastrointestinal symptoms, and markers of immune function in elite rugby union players. METHODS Thirty-three elite rugby union players were randomly assigned to consume a prebiotic (2.8 g/day galactooligosaccharide) or placebo (2.8 g/day maltodextrin), daily for 168 days under double-blind conditions. Participants completed daily and weekly questionnaires for self-reported upper respiratory and gastrointestinal symptoms respectively. Blood and saliva samples were collected at 0, 84, and 168 days for assessment of plasma TNF-α and CRP, and saliva IgA respectively. RESULTS The prebiotic group experienced a 2-day reduction in upper respiratory symptom duration (P = 0.045). Gastrointestinal symptom severity and incidence were lower in the prebiotic group compared to the placebo group (P < 0.001, P = 0.041) respectively. Salivary immunoglobulin A secretion rate was 42% greater in the prebiotic group compared to the placebo group at day 168 (P = 0.004), no differences in CRP and TNF-α were found (P > 0.05). CONCLUSION A 168-day dietary prebiotic intervention reduced the duration of upper respiratory symptoms and reduced the incidence and severity of gastrointestinal symptoms in elite rugby union players. These findings suggest that seasonal prebiotic interventions may be beneficial for reducing illness in elite rugby union players, improving their availability to train and compete.Key pointsElite athletes are susceptible to upper respiratory symptoms and gastrointestinal symptoms which may impact upon training availability and competition performance.For the first time, this study shows that a dietary prebiotic intervention can reduce the duration of upper respiratory symptoms by 2 days in elite rugby union players.Dietary prebiotic supplementation can improve the incidence and severity of gastrointestinal symptoms experienced by elite rugby union players.Prebiotic supplementation was able to increase salivary IgA secretion after 168 days.These findings can inform practice suggesting that seasonal prebiotic use has the potential to modulate immune function and reduce illness in elite rugby union, which may improve a player's availability to train and compete.The mechanisms by which prebiotics reduce URS and GIS require further research exploration.
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Inulin-type fructans and 2'fucosyllactose alter both microbial composition and appear to alleviate stress-induced mood state in a working population compared to placebo (maltodextrin): the EFFICAD Trial, a randomized, controlled trial.
Jackson, PP, Wijeyesekera, A, Williams, CM, Theis, S, van Harsselaar, J, Rastall, RA
The American journal of clinical nutrition. 2023;118(5):938-955
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Anxiety and depression are the most common mental health disorders and a bidirectional relationship exists between the gut and the brain, the gut-brain axis, which may be mediated by metabolites of the gut microbiome, which include various neurotransmitters. Prebiotics, such as 2'fucosyllactose (2FS, a human milk oligosaccharide) and oligofructose (OF, an inulin-type fructan) can modulate the microbiome and may as such affect mood. The aim of this double-blind, randomised-controlled trial, including 96 healthy adults with mild/moderate levels of stress/anxiety, was to evaluate the effect of a 4-week course of 2FS and OF individually and combined versus maltodextrin (as a placebo) on the microbiome and mood. Significant positive changes in the microbiome were seen in the OF and the OF+2FS groups, compared to control. Improvements in mood (anxiety, depression, positive and negative affect and cortisol awakening response) were seen in all 3 intervention groups compared to control but generally stronger in the OF and the OF+2FS groups. The authors concluded that OF alone and in combination with 2FS has beneficial effects for mood and microbiome composition, whilst the effects on the microbiome of 2FS alone require further study.
Abstract
BACKGROUND There is increasing interest in the bidirectional relationship existing between the gut and brain and the effects of both oligofructose and 2'fucosyllactose to alter microbial composition and mood state. Yet, much remains unknown about the ability of oligofructose and 2'fucosyllactose to improve mood state via targeted manipulation of the gut microbiota. OBJECTIVES We aimed to compare the effects of oligofructose and 2'fucosyllactose alone and in combination against maltodextrin (comparator) on microbial composition and mood state in a working population. METHODS We conducted a 5-wk, 4-arm, parallel, double-blind, randomized, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomized to oligofructose 8 g/d (plus 2 g/d maltodextrin); maltodextrin 10 g/d; oligofructose 8 g/d plus 2'fucosyllactose (2 g/d) or 2'fucosyllactose 2 g/d (plus 8 g/d maltodextrin). Changes in microbial load (fluorescence in situ hybridization-flow cytometry) and composition (16S ribosomal RNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits, and mood state parameters. RESULTS There were significant increases in several bacterial taxa including Bifidobacterium, Bacteroides, Roseburia, and Faecalibacterium prausnitzii in both the oligofructose and oligofructose/2'fucosyllactose interventions (all P ≤ 0.05). Changes in bacterial taxa were highly heterogenous upon 2'fuscoyllactose supplementation. Significant improvements in Beck Depression Inventory, State Trait Anxiety Inventory Y1 and Y2, and Positive and Negative Affect Schedule scores and cortisol awakening response were detected across oligofructose, 2'fucosyllactose, and oligofructose/2'fucosyllactose combination interventions (all P ≤ 0.05). Both sole oligofructose and oligofructose/2'fuscosyllactose combination interventions outperformed both sole 2'fucosyllactose and maltodextrin in improvements in several mood state parameters (all P ≤ 0.05). CONCLUSION The results of this study indicate that oligofructose and combination of oligofructose/2'fucosyllactose can beneficially alter microbial composition along with improving mood state parameters. Future work is needed to understand key microbial differences separating individual responses to 2'fucosyllactose supplementation. This trial was registered at clinicaltrials.gov as NCT05212545.
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Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses to an Arithmetic Stress Task in Healthy Subjects: A Randomised Clinical Trial and Proof-of-Concept Study.
Edebol Carlman, HMT, Rode, J, König, J, Repsilber, D, Hutchinson, AN, Thunberg, P, Persson, J, Kiselev, A, Pruessner, JC, Brummer, RJ
Nutrients. 2022;14(7)
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Physiological and psychological stress can affect gut function and its interaction with the brain (gut-brain axis). Different types of stress and different phases of stress regulation can affect the brain in different ways. Manipulation of the gut microbiota using probiotic bacteria has been shown to improve cognition and stress response. However, probiotic interventions are likely to have different effects depending on the strains used. The aim of this study was to assess the effects of a probiotic intervention on brain activity and stress response. This study is a randomised double-blinded placebo-controlled crossover study with 22 healthy subjects. Subjects were randomised to two study groups receiving the intervention in different orders (probiotics or placebo first). Results demonstrate that the probiotic intervention: - altered activity in specific brain regions known to regulate emotion and stress response. - significantly altered functional connectivity between the upper limbic and medioventral regions. - did not affect the activation of other limbic or subcortical areas. Authors conclude that their findings could further lead to possible clinical implications for improving stress resilience and potential roles in the treatment of affective and gut-brain axis disorders.
Abstract
Probiotics are suggested to impact physiological and psychological stress responses by acting on the gut-brain axis. We investigated if a probiotic product containing Bifidobacterium longum R0175, Lactobacillus helveticus R0052 and Lactiplantibacillus plantarum R1012 affected stress processing in a double-blinded, randomised, placebo-controlled, crossover proof-of-concept study (NCT03615651). Twenty-two healthy subjects (24.2 ± 3.4 years, 6 men/16 women) underwent a probiotic and placebo intervention for 4 weeks each, separated by a 4-week washout period. Subjects were examined by functional magnetic resonance imaging while performing the Montreal Imaging Stress Task (MIST) as well as an autonomic nervous system function assessment during the Stroop task. Reduced activation in regions of the lateral orbital and ventral cingulate gyri was observed after probiotic intervention compared to placebo. Significantly increased functional connectivity was found between the upper limbic region and medioventral area. Interestingly, probiotic intervention seemed to predominantly affect the initial stress response. Salivary cortisol secretion during the task was not altered. Probiotic intervention did not affect cognitive performance and autonomic nervous system function during Stroop. The probiotic intervention was able to subtly alter brain activity and functional connectivity in regions known to regulate emotion and stress responses. These findings support the potential of probiotics as a non-pharmaceutical treatment modality for stress-related disorders.
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Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: A double-blind, randomized, placebo-controlled study.
Gomi, A, Yamaji, K, Watanabe, O, Yoshioka, M, Miyazaki, K, Iwama, Y, Urita, Y
Journal of dairy science. 2018;101(6):4830-4841
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Probiotics have been found to have beneficial effects in adults with functional gastrointestinal (GI) disorders, however little evidence exists regarding its effects on healthy adults. The aim of this prospective, randomised, double-blind, placebo-controlled, parallel-group trial was to clarify the beneficial effects of Bifidobacterium bifidum (B bifidum) on gastric symptoms in 100 healthy Japanese adults who experience temporary GI symptoms. Participants were randomised to consume active fermented milk or placebo milk matched for colour, taste and packaging daily for four weeks and various qualitative and quantitative measurements were assessed. This trial found the group consuming B bifidum experienced significantly better relief from upper GI symptoms compared with the placebo group. These findings suggest daily consumption of milk fermented with B bifidum helps relive GI discomfort and symptoms in healthy adults with no risk of side effects. Based on these results, the authors conclude fermented milk drinks can be recommended to patients who experience temporary GI pain.
Abstract
In a preliminary open-label trial by our group, Bifidobacterium bifidum YIT 10347 (YIT10347) relieved gastric symptoms in patients with functional gastrointestinal disorders. Hence, in this study, we investigated the effects of YIT10347 on gastrointestinal symptoms in healthy adults. In this prospective double-blind, randomized, placebo-controlled trial (UMIN000024654), 100 healthy Japanese adults were randomly assigned to a YIT10347 group or placebo group and consumed 100 mL of YIT10347-fermented milk or placebo fermented milk, respectively, every day for 4 wk. Gastrointestinal symptoms were evaluated by using the modified Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (m-FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) as primary endpoints. Mental symptoms, quality of life, salivary stress markers, and gastric emptying were evaluated as secondary endpoints. Effectiveness and safety were analyzed in a per-protocol set (YIT10347 group, n = 39; placebo group, n = 40) and full analysis set (YIT10347 group, n = 50; placebo group, n = 50), respectively. In the m-FSSG evaluation, the YIT10347 group had a significantly higher relief rate of postprandial discomfort and greater changes in postprandial epigastric pain score from baseline than the placebo group. In the GSRS evaluation, the YIT10347 group had significantly higher relief rates of overall gastrointestinal symptoms, upper gastrointestinal symptoms, flatus, and diarrhea than the placebo group. We detected no significant differences in scores or relief rates of mental symptoms and quality of life, a salivary stress marker, or gastric emptying between the 2 groups. No severe adverse events associated with test beverage consumption were observed in either group. These findings suggest that daily consumption of YIT10347-fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms such as postprandial discomfort and epigastric pain in healthy adults.
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Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults.
Vanegas, SM, Meydani, M, Barnett, JB, Goldin, B, Kane, A, Rasmussen, H, Brown, C, Vangay, P, Knights, D, Jonnalagadda, S, et al
The American journal of clinical nutrition. 2017;105(3):635-650
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Increased whole grain consumption has been associated with reduced levels of inflammation. This randomised, controlled trial aimed to assess the effects of a whole grain diet in comparison with a refined grain diet on the immune system, levels of inflammation and gut bacteria. 81 men and women aged between 40 and 60 were randomly assigned to either a whole grain or a refined grain diet for a period of 6 weeks. All other dietary components were kept the same and calorie levels were controlled to maintain weight levels. The study findings showed a positive effect on stool frequency and stool weight with the whole grain diet in comparison to the refined grain diet. The whole grain diet also showed modest positive effects on gut bacteria profiles and aspects of immunity. The whole grain diet showed no effects on markers of inflammation.
Abstract
Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity.Objective: We assessed the effects of diets rich in WGs compared with refined grains (RGs) on immune and inflammatory responses, gut microbiota, and microbial products in healthy adults while maintaining subject body weights.Design: After a 2-wk provided-food run-in period of consuming a Western-style diet, 49 men and 32 postmenopausal women [age range: 40-65 y, body mass index (in kg/m2) <35] were assigned to consume 1 of 2 provided-food weight-maintenance diets for 6 wk.Results: Compared with the RG group, the WG group had increased plasma total alkyresorcinols (a measure of WG intake) (P < 0.0001), stool weight (P < 0.0001), stool frequency (P = 0.02), and short-chain fatty acid (SCFA) producer Lachnospira [false-discovery rate (FDR)-corrected P = 0.25] but decreased pro-inflammatory Enterobacteriaceae (FDR-corrected P = 0.25). Changes in stool acetate (P = 0.02) and total SCFAs (P = 0.05) were higher in the WG group than in the RG group. A positive association was shown between Lachnospira and acetate (FDR-corrected P = 0.002) or butyrate (FDR-corrected P = 0.005). We also showed that there was a higher percentage of terminal effector memory T cells (P = 0.03) and LPS-stimulated ex vivo production of tumor necrosis factor-α (P = 0.04) in the WG group than in the RG group, which were positively associated with plasma alkylresorcinol concentrations.Conclusion: The short-term consumption of WGs in a weight-maintenance diet increases stool weight and frequency and has modest positive effects on gut microbiota, SCFAs, effector memory T cells, and the acute innate immune response and no effect on other markers of cell-mediated immunity or systemic and gut inflammation. This trial was registered at clinicaltrials.gov as NCT01902394.