Abstract

OBJECTIVE Animal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fibre on reward-related food decision-making in a randomised controlled within-subject cross-over study and assayed potential microbial and metabolic markers. DESIGN 59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/day of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool. RESULTS Compared with placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (preregistered, family wise error-corrected p <0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producing Bifidobacteriaceae, and changes in >60 predicted functional signalling pathways after prebiotic intake. Changes in brain activation correlated with changes in Actinobacteria microbial abundance and associated activity previously linked with SCFA production, such as ABC transporter metabolism. CONCLUSIONS In this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food decision-making, paralleled by shifts in gut microbiota. TRIAL REGISTRATION NUMBER NCT03829189.

Abstract

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

Abstract

BACKGROUND Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels. METHODS We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement. RESULTS A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: -0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: -0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: -0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found. CONCLUSIONS Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves' disease.

Abstract

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884. What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber – gut microbiota (Anaerostipes)—constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

Abstract

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.

Abstract

Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.

Abstract

BACKGROUND Gut microbiota of pregnant women change with the gestational week. On the one hand, they participate in the metabolic adaptation of pregnant women. On the other hand, the abnormal composition of gut microbiota of pregnant women is more likely to suffer from gestational diabetes mellitus (GDM). Therefore, gut microbiota targeted treatment through dietary supplements is particularly important for prevention or treatment. Prebiotic supplements containing galactooligosaccharides (GOS) may be an intervention method, but the effect is still unclear. OBJECTIVE This study aims to evaluate the feasibility and acceptability of prebiotic intervention in healthy pregnant women during pregnancy, and to explore the possible effects of intervention on pregnant women and the influence on gut microbiota as preliminaries. METHODS After recruitment in first trimester, 52 pregnant women were randomly assigned to receive GOS intervention or placebo containing fructooligosaccharides. 16S rRNA sequencing technology was used to detect the composition, diversity and differential flora of gut microbiota. Lipid metabolism, glucose metabolism and inflammatory factors during pregnancy were also analyzed. RESULTS The adverse symptoms of GOS intervention are mild and relatively safe. For pregnant women, there was no significant difference in the GDM incidence rates and gestational weight gain (GWG) in the GOS group compared with placebo (P > 0.05). Compared with the placebo group, the levels of FPG, TG, TC, HDL-C LDL-C, and IL-6 had no significant difference in GOS group (P > 0.05). For newborns, there was no significant difference between GOS group and placebo group in the following variables including gestational week, birth weight, birth length, head circumference, chest circumference, sex, and delivery mode (P > 0.05). And compared with the placebo group, the GOS group had a higher abundance of Paraprevotella and Dorea, but lower abundance of LachnospiraceaeUCG_001. CONCLUSIONS GOS prebiotics appear to be safe and acceptable for the enrolled pregnancies. Although GOS intervention did not show the robust benefits on glucose and lipid metabolism. However, the intervention had a certain impact on the compostion of gut microbiota. GOS can be considered as a dietary supplement during pregnancy, and further clinical studies are needed to explore this in the future.

Abstract

BACKGROUND Sorghum is a cereal source of energy, carbohydrates, resistant starch, proanthocyanidins, and 3-deoxyanthocyanins; it promotes satiety by slowing digestion and benefits intestinal health. OBJECTIVE This study investigated the effects of extruded sorghum SC319 consumption on intestinal health, weight loss, and inflammatory markers in men with overweight. METHODS This was a randomized, controlled, single-blind clinical trial. Twenty-one men were randomly allocated into one of two groups: the sorghum group (test), which received 40 g of extruded SC319 whole sorghum (n = 10), or the wheat group (control), which received 38 g of extruded whole wheat (n = 11) for eight weeks. RESULTS The sorghum consumption increased the weight loss intragroup, decreased the body fat percentage intergroup, and did not change inflammatory markers, while the wheat group had increased IL-6 levels compared to baseline. Short-chain fatty acid production, fecal pH, and α and β diversity indexes did not differ intra- and intergroup after interventions. However, sorghum consumption decreased genus levels of Clostridium_sensu_stricto 1, Dorea, and Odoribacter and increased CAG-873 and Turicibacter compared to baseline. Further, sorghum showed a tendency (p = 0.07) to decrease the proteobacteria phyla compared to wheat. CONCLUSION Extruded sorghum SC319 improved intestinal microbiota and body composition and promoted weight loss, demonstrating its prebiotic potential.

Abstract

BACKGROUND COVID-19 disease is a serious global health problem. Few treatments have been shown to reduce mortality and accelerate time to recovery. The aim of this study was to evaluate the potential effect of a food supplement (probiotics, prebiotics, vitamin D, zinc and selenium) in patients admitted with COVID-19. METHODS A prospective randomized non-blinded clinical trial was conducted in a sample of 162 hospitalized patients diagnosed with COVID-19 recruited over eight months. All patients received standard treatment, but the intervention group (n = 67) was given one food supplement stick daily during their admission. After collecting the study variables, a statistical analysis was performed comparing the intervention and control groups and a multivariate analysis controlling for variables that could act as confounding factors. RESULTS ROC curve analysis with an area under the curve (AUC) value of 0.840 (p < 0.001; 95%CI: 0.741-0.939) of the food supplement administration vs. recovery indicated good predictive ability. Moreover, the intervention group had a shorter duration of digestive symptoms compared with the control group: 2.6 ± 1.3 vs. 4.3 ± 2.2 days (p = 0.001); patients with non-severe disease on chest X-ray had shorter hospital stays: 8.1 ± 3.9 vs. 11.6 ± 7.4 days (p = 0.007). CONCLUSIONS In this trial, the administration of a food supplement (Gasteel Plus®) was shown to be a protective factor in the group of patients with severe COVID-19 and allowed early recovery from digestive symptoms and a shorter hospital stay in patients with a normal-mild-moderate chest X-ray at admission (ClinicalTrials.gov number, NCT04666116).

Abstract

BACKGROUND Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.