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Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial.
Pietrzak, A, Banasiuk, M, Szczepanik, M, Borys-Iwanicka, A, Pytrus, T, Walkowiak, J, Banaszkiewicz, A
Nutrients. 2022;14(16)
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Inflammatory bowel diseases (IBD), such as Crohn’s Disease and ulcerative colitis, are chronic gastrointestinal disorders with periods of exacerbation and remission. The disease develops as a result of an abnormal immune response in the gastrointestinal mucosa in genetically predisposed individuals exposed to certain environmental conditions. The primary aim of this study was to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. This study is a prospective, randomised, and placebo-controlled trial. Patients (n = 80) were randomised and assigned to one of two groups: group A received butyric acid at a dose of 150 mg, and group B received 150 mg placebo. Results show that supplementation with sodium butyrate to be ineffective in the add-on treatment of newly diagnosed children and adolescents with IBD. Furthermore, during the study, none of the participants reported adverse events. Authors conclude that the results of their study will contribute to further studies that will determine which patients with IBD may benefit from sodium butyrate supplementation. Further clinical trials on large groups of patients are needed to establish if IBD patients may benefit from sodium butyrate.
Abstract
BACKGROUND Butyric acid's effectiveness has not yet been assessed in the pediatric inflammatory bowel disease (IBD) population. This study aimed to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. METHODS This was a prospective, randomized, placebo-controlled multicenter study. Patients aged 6-18 years with colonic Crohn's disease or ulcerative colitis, who received standard therapy depending on the disease's severity, were randomized to receive 150 mg sodium butyrate twice a day (group A) or placebo (group B). The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study. RESULTS In total, 72 patients with initially active disease completed the study, 29 patients in group A and 43 in group B. At week 12 of the study, the majority of patients achieved remission. No difference in remission rate or median disease activity was found between the two groups (p = 0.37 and 0.31, respectively). None of the patients reported adverse events. CONCLUSIONS A 12-week supplementation with sodium butyrate, as adjunctive therapy, did not show efficacy in newly diagnosed children and adolescents with IBD.
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Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants.
Samara, J, Moossavi, S, Alshaikh, B, Ortega, VA, Pettersen, VK, Ferdous, T, Hoops, SL, Soraisham, A, Vayalumkal, J, Dersch-Mills, D, et al
Cell host & microbe. 2022;30(5):696-711.e5
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Preterm infants display a disrupted and potentially pathogenic gut microbiome compared to infants born at full term. They are also more likely to be born by caesarean section, receive antibiotics and remain in hospital for an extended period, all which can contribute to gut microbiota disruptions. Probiotics are increasingly being given to preterm infants to counteract the disruptions; however, their effects are under researched in this cohort of individuals. This randomised control trial of 57 extremely premature infants aimed to determine the effects of a probiotic supplement on gut microbiota composition and their effects on gut immunity. The results showed that Bifidobacterium strains could colonise the premature infant gut but not Lactabacillus rhamnosus. Probiotics also accelerated the maturation of the gut microbiome in premature infants and Bifidobacterium were responsible for this resulting in an anti-inflammatory effect in the gut. It was concluded that probiotic supplementation with the right microbes can act to mature the gut microbiome of preterm infants resulting in its restoration and associated health benefits. This study could be used by healthcare professionals to understand that preterm infants may have a disordered gut microbiota, but a healthy community can be restored through using a probiotic containing Bifidobacterium.
Abstract
Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.
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Term infant formula supplemented with milk-derived oligosaccharides shifts the gut microbiota closer to that of human milk-fed infants and improves intestinal immune defense: a randomized controlled trial.
Estorninos, E, Lawenko, RB, Palestroque, E, Sprenger, N, Benyacoub, J, Kortman, GAM, Boekhorst, J, Bettler, J, Cercamondi, CI, Berger, B
The American journal of clinical nutrition. 2022;115(1):142-153
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Human milk is finely attuned to the needs of infants supporting optimal growth and overall development. Infant formula composition is developed after human milk. A promising novel approach to enhance the oligosaccharide profile of infant formulas is the addition of bovine milk-derived oligosaccharides (MOS). The aim of this study was to investigate the effects of a MOS-supplemented infant formula on gut microbiota and intestinal immunity. This study was a randomised, double-blind, controlled trial of 2 formula fed groups and a prospective, observational companion study of human milk-fed infants (HFI). Formula-fed infants (n = 230) were randomly assigned to either the control group (CG) or experimental group (EG). Results showed that adding MOS to infant formula had a strong effect on gut microbiota particularly noticeable was a significant increase in bifidobacteria. Furthermore, the effects of the MOS-supplemented formula on the gut microbiota in caesarean- or vaginally born infants were similar, changing the microbiota towards the composition of vaginally born HFI including an increase in bifidobacteria. Authors conclude that the gut microbiota and intestinal immunity of formula-fed infants can be beneficially modulated by an infant formula with an oligosaccharide profile enhanced by the addition of MOS. Thus, supplementing infant formula with MOS is a promising approach to support the development of the gut microbiota during early infancy in concert with the infant’s immune development.
Abstract
BACKGROUND Bovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent concentrations of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile. OBJECTIVE To investigate the effects of an MOS-supplemented infant formula on gut microbiota and intestinal immunity. METHODS In a double-blind, randomized, controlled trial, healthy term formula-fed infants aged 21-26 d either received an intact protein cow milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until the age of 6 mo. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as the reference. Fecal samples collected at baseline, and the ages of 2.5 and 4 mo were assessed for microbiota (16S ribosomal RNA-based approaches), metabolites, and biomarkers of gut health and immune response. RESULTS Aged 2.5 and 4 mo, redundancy analysis (P = 0.002) and average phylogenetic distance (P < 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally born infants and approaching HFI vaginally born infants. Relative bifidobacteria abundance was higher in EG compared with CG (P < 0.05) approaching HFI. At the age of 4 mo, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P < 0.001) and ∼65% (P < 0.01) lower in EG compared with CG, respectively. Geometric LS mean (95% CI) fecal secretory IgA in EG was twice that of CG [70 (57, 85) compared with 34 (28, 42) mg/g, P < 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG compared with CG (P = 0.065). Compared with CG, EG and HFI had lower fecal calcium excretion (by ∼30%, P < 0.005) and fecal pH (P < 0.001), and higher lactate concentration (P < 0.001). CONCLUSIONS Infant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves the intestinal immune response.
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Effects of Lactiplantibacillus plantarum OLL2712 on Memory Function in Older Adults with Declining Memory: A Randomized Placebo-Controlled Trial.
Sakurai, K, Toshimitsu, T, Okada, E, Anzai, S, Shiraishi, I, Inamura, N, Kobayashi, S, Sashihara, T, Hisatsune, T
Nutrients. 2022;14(20)
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On the Alzheimer’s disease spectrum, which is the most common cause of dementia, the typical symptom at onset is impaired memory. As the disease progresses, other cognitive domains, such as language, visuospatial cognition, and executive function, are impaired, gradually making it impossible to maintain independence in daily life. The aim of this study was to test the protective effects of 12 weeks of supplementation with heat-treated Lactiplantibacillus OLL2712 cells on memory function in older adults. This study was a double-blind placebo-controlled trial in which participants were randomly assigned to the active or placebo group. Results showed that OLL2712 consumption had a protective effect on memory function in older adults. However, there was no significant effect of OLL2712 intake on verbal memory in either of the analyses. Furthermore, in the gut microbiota analysis, the bacterial composition of the active group showed significantly lower abundance ratios of bacterial species linked to inflammation (Lachnoclostridium, Monoglobus, and Oscillibacter). Authors conclude that continuous intake of OLL2712 may be an effective approach to protect memory function in older adults.
Abstract
The use of probiotics is expected to be an intervention in neurodegenerative conditions that cause dementia owing to their ability to modulate neuroinflammatory responses via the microbiome-gut-brain axis. Therefore, we selected Lactiplantibacillus plantarum OLL2712 (OLL2712), the optimal anti-inflammatory lactic acid bacteria strain with high IL-10-inducing activity in immune cells, and aimed to verify its protective effects on memory function in older adults. A 12-week, randomized, double-blind, placebo-controlled trial was performed with older adults over the age of 65 years with declining memory. The participants consumed either powder containing heat-treated OLL2712 cells or placebo. Memory function was assessed using a computer-assisted cognitive test, Cognitrax. Daily dietary nutrient intake was assessed using the Brief-type Self-administered Diet History Questionnaire (BDHQ). The composition of the gut microbiota was analyzed by fecal DNA extraction and 16S rDNA sequencing. Data from 78 participants who completed the entire procedure were analyzed, and significant improvements in composite memory and visual memory scores were observed in the active group, after accounting for the effect of daily nutritional intake (p = 0.044 and p = 0.021, respectively). In addition, the active group had a lower abundance ratio of Lachnoclostridium, Monoglobus, and Oscillibacter genera, which have been reported to be involved in inflammation. The present study suggests that OLL2712 ingestion has protective effects against memory function decline in older adults.
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Effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in patients with fibromyalgia.
Baldi, S, Pagliai, G, Dinu, M, Di Gloria, L, Nannini, G, Curini, L, Pallecchi, M, Russo, E, Niccolai, E, Danza, G, et al
World journal of gastroenterology. 2022;28(18):1965-1980
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Fibromyalgia (FM) is a systemic syndrome of unclear aetiology, characterized by widespread pain and tenderness, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting a potential involvement of the gut microbiota (GM), as demonstrated by the frequent dysbiosis found in FM subjects. The aim of this study was to examine whether a replacement diet with ancient Khorasan wheat could influence the GM composition, the faecal molecular immune profile, and short-chain fatty acids (SCFAs) production in patients suffering fibromyalgia syndrome. This study was a randomised, double-blind crossover trial which enrolled patients with documented FM who consumed control wheat products or Khorasan wheat products for 8 weeks and then crossed over. Participants (n=20) were randomly assigned to one of the two groups. Results showed that: - both 8-week interventions did not significantly modify either the microbial composition and diversity or the SCFAs levels; - in terms of changes in microbial abundances produced by each dietary intervention, Khorasan wheat products (KD) did not result in modifications at any taxonomic level, whereas the controlled diet (CD) was associated with a significant increase of Turicibacter spp. [bacteria belonging to the phylum Firmicutes]; - faecal molecular inflammatory profile showed that CD resulted in an increased level of a particular anti-inflammatory marker, while no significant differences were reported after KD. Authors conclude that an ancient Khorasan wheat diet results in some beneficial GM compositional and functional modifications that positively correlate with an improvement of fibromyalgia symptomatology.
Abstract
BACKGROUND Fibromyalgia (FM) syndrome is mainly characterized by widespread pain, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting the potential pathogenic role of the gut microbiota (GM). The GM is deeply influenced by several environmental factors, especially the diet, and recent findings highlighted significant symptom improvement in FM patients following various nutritional interventions such as vegetarian diet, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols based diets, gluten-free diet, and especially an ancient grain supplementation. In particular, a recent study reported that a replacement diet with ancient Khorasan wheat led to an overall improvement in symptom severity of FM patients. AIM: To examine the effects of ancient Khorasan wheat on the GM, inflammation, and short-chain fatty acid production in FM patients. METHODS After a 2-wk run-in period, 20 FM patients were enrolled in this randomized, double-blind crossover trial. In detail, they were assigned to consume either Khorasan or control wheat products for 8 wk and then, following an 8-wk washout period, crossed. Before and after treatments, GM characterization was performed by 16S rRNA sequencing while the fecal molecular inflammatory response and the short-chain fatty acids (SCFAs) were respectively determined with the Luminex MAGPIX detection system and a mass chromatography-mass spectrometry method. RESULTS The Khorasan wheat replacement diet, in comparison with the control wheat diet, had more positive effects on intestinal microbiota composition and on both the fecal immune and SCFAs profiles such as the significant increase of butyric acid levels (P = 0.054), candidatus Saccharibacteria (P = 9.95e-06) and Actinobacteria, and the reduction of Enterococcaceae (P = 4.97e-04). Moreover, the improvement of various FM symptoms along with the variation of some gut bacteria after the Khorasan wheat diet have been documented; in fact we reported positive correlations between Actinobacteria and both Tiredness Symptoms Scale (P < 0.001) and Functional Outcome of Sleep Questionnaire (P < 0.05) scores, between Verrucomicrobiae and both Widespread Pain Index (WPI) + Symptom Severity scale (SS) (P < 0.05) and WPI (P < 0.05) scores, between candidatus Saccharibacteria and SS score (P < 0.05), and between Bacteroidales and Sleep-Related and Safety Behaviour Questionnaire score (P < 0.05). CONCLUSION The replacement diet based on ancient Khorasan wheat results in beneficial GM compositional and functional modifications that positively correlate with an improvement of FM symptomatology.
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Effects of Lactococcus lactis subsp. cremoris YRC3780 daily intake on the HPA axis response to acute psychological stress in healthy Japanese men.
Matsuura, N, Motoshima, H, Uchida, K, Yamanaka, Y
European journal of clinical nutrition. 2022;76(4):574-580
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The hypothalamic-pituitary-adrenal (HPA) axis is involved in the stress response and is linked to the microbiome through a number of possible mechanisms, including immune-related ones. Lactococcus lactis subsp. cremoris YRC3780 (YRC3780), a probiotic isolated from kefir, has been shown to have beneficial immune-modulatory properties. The aim of this double-blind, placebo-controlled trial, which included 27 healthy young men, was to assess sleep quality, mental health, HPA axis activity (salivary cortisol) and response to an acute stress test during/after 8 weeks of supplementation with YRC3780. At 8 weeks, salivary morning cortisol levels were significantly reduced in the probiotic compared to the placebo group. The effect on the stress test depended on whether or not participants were considered “cortisol-responders” or not. Improvements in sleep quality were seen at 6 weeks (but not at any other time points) in 1 out of 2 sleep questionnaires in the YRC3780 group, whilst no significant differences were observed in actigraphy-measured sleep efficiency. There were no differences in mood between groups, but significant improvements in general health in the probiotic group. Interestingly, no changes in the microbiome of the probiotic group were seen, suggesting that the observed effects may be mediated via the immune system.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Research indicates a bidirectional interaction between the gut microbiome and the central nervous system, affecting the functions of the brain and spinal cord.
- This clinical trial suggests that daily intake of Lactococcus lactis subsp. cremoris (YRC3780) may enhance the HPA axis response to acute psychological stress, potentially linked to a reduction in morning cortisol levels.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A randomized, placebo-controlled, double-blind clinical trial was conducted to investigate the influence of Lactococcus lactis subsp. cremoris (YRC3780), isolated from kefir, on stress response, sleep quality, and mental health.
Method
Twenty-seven healthy young men, with an average age of 23.5 years, and mean body mass index of 21.5 kg/m2 , were randomly assigned to either the YRC3780 group or the placebo group. Participants were administered YRC3780 or a placebo daily for 8 weeks.
Throughout the study, participants completed assessments, including the Athens Insomnia Scale (AIS), the Pittsburgh Sleep Quality Index (PSQI), the General Health Questionnaire (GHQ-28), and the Profile of Mood States 2nd Edition-Adult Short, Total Mood Disturbance subscale (POMS 2 TMD), every 2 weeks. Additionally, diurnal rhythms of HPA axis activity were assessed every 2 weeks through saliva samples collected at 2-hour intervals during the day. At the end of the 8-week supplementation period, participants underwent the Trier Social Stress Test (TSST) to evaluate the effects of daily YRC3780 intake on the HPA axis stress response. In addition, three fecal samples were collected to analyse the gut microbiome (on the last day of baseline, and at 4 and 8 weeks).
A total of 27 out of 33 subjects (81%) completed the study, with six participants withdrawing without providing explanations.
Results
The primary findings of this study were as follows:
- At week 6 of YRC3780 supplementation, salivary cortisol levels at 2 hours and 6 hours after waking were significantly lower in the YRC3780 group compared to the placebo group (p=0.05).
- Salivary cortisol concentrations at 40 minutes after the TSST were significantly lower in the YRC3780 group (4.2 ± 4.4 nmol/L, mean ± SD) than in the placebo group (7.6 ± 4.7 nmol/L) (p=0.043).
- AIS scores at 6 weeks and GHQ-28 scores at 8 weeks were significantly lower in the YRC3780 group compared to the placebo group (AIS, p=0.031; GHQ-28, p=0.038) indicating better sleep quality and a better mental state.
Conclusion:
Oral supplementation with YRC3780 may have beneficial effects on the HPA axis response to acute psychological stress, potentially associated with a decrease in morning cortisol levels. Additionally, the study suggests that the lower basal activity and stress reactivity of the HPA axis may lead to improvements in subjective sleep quality and mental health.
Clinical practice applications:
- The precise mechanisms underlying the correlation between the gut microbiota and the gut-brain axis remain incompletely understood, emphasising the need for further research.
- This clinical trial demonstrated that daily intake of YRC3780 decreased morning salivary cortisol levels at 6 and 8 weeks and reduced the salivary cortisol response to acute psychological stress.
Considerations for future research:
- Larger, adequately powered clinical trials are required to provide deeper insights into the mechanisms responsible for the stress-reducing and sleep-improving effects of Lactococcus lactis subsp. cremoris.
- Furthermore, investigations into optimal dosage and duration of probiotic supplementation are warranted for a more comprehensive understanding, particularly in diverse demographic groups.
- Comparative research is needed to explore the effects of various probiotic strains on objective stress responses.
Abstract
BACKGROUND Lactococcus lactis subsp. cremoris (YRC3780), which is isolated from kefir, has been associated with anti-allergic effects in humans. However, it remains unknown whether daily intake of YRC3780 attenuates the response to psychological stress in humans in parallel with changes to the gut microbiome. We examined the fundamental role of YRC3780 in the gut microbiome, stress response, sleep, and mental health in humans. METHODS Effects of daily intake of YRC3780 on the hypothalamic-pituitary-adrenal (HPA) axis response to acute psychological stress were investigated in a double-blind, placebo-controlled clinical trial involving 27 healthy young men (mean age and body mass index: 23.5 years and 21.5 kg/m2) who were randomly assigned to placebo (n = 13) or YRC3780 (n = 14) groups. The HPA axis response to acute psychological stress, the diurnal rhythm of HPA axis activity, and gut microbiome were assessed and compared between the two groups. RESULTS The results showed that daily intake of YRC3780 significantly lowered morning salivary cortisol levels compared with placebo. In addition, salivary cortisol levels following a social stress test significantly decreased +40 min after beginning the TSST in the YRC3780-treated group compared to placebo. There were no significant differences between the two groups in terms of actigraphy-based sleep quality, but the subjective sleep quality and mental health were significantly improved in the YRC3780-treated group compared to placebo. CONCLUSIONS Our study suggests that daily intake of YRC3780 improves the HPA axis response to acute psychological stress, which might be associated with a decrease in morning cortisol levels.
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Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.
Song, SJ, Wang, J, Martino, C, Jiang, L, Thompson, WK, Shenhav, L, McDonald, D, Marotz, C, Harris, PR, Hernandez, CD, et al
Med (New York, N.Y.). 2021;2(8):951-964.e5
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Studies on model organisms show that foetal development can be modulated by microbial products from the pregnant mother’s microbiota, and early colonisation is critical for immune system development. However, natural transmission and colonisation of maternal microbes is impaired by caesarean section (CS) delivery. The aim of this study was to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. This study is a large observational study of 177 infants born to 174 mothers. Physicians assessed healthy mothers who were set to deliver vaginally or by scheduled CS. Results demonstrate that microbial differences associated with delivery mode can be reduced by exposure to a vaginal microbial source at birth. In fact, birth mode significantly differentiated infant gut and skin microbiome development, and that seeding worked to adjust the trajectory of CS-delivered infants through partial restoration of microbiome features associated with a vaginal delivery. Authors conclude that restoring natural exposures at birth may be one way to reduce the risk of CS-associated diseases such as obesity, asthma, allergies, and immune disfunctions. However, randomised clinical trials on large cohorts are needed to gain conclusive evidence for microbial restoration at birth improving health outcomes.
Abstract
BACKGROUND Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth. METHODS Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth. FINDINGS Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study. CONCLUSIONS The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth. FUNDING C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.
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The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol.
Karakula-Juchnowicz, H, Rog, J, Juchnowicz, D, Łoniewski, I, Skonieczna-Żydecka, K, Krukow, P, Futyma-Jedrzejewska, M, Kaczmarczyk, M
Nutrition journal. 2019;18(1):50
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Major depressive disorder (MDD) has historically been recognised as a brain disease, however more recently it is being recognised as a whole-body disorder. The immune system and the gut microbiota have been implicated in MDD with particular focus on the gut wall integrity and the resultant immune reaction and its influence on the brain. Gluten may incite an immune reaction in certain individuals and a gluten free diet may be of benefit to symptoms of depression in those who have gluten-related disorders. This randomised prospective control trial of 120 patients with MDD aims to determine the effect of a gluten free diet and probiotic supplementation in symptom management over 12 weeks. As this was a prospective study, no results were achieved. However, the study does indicate that randomised control trials on the effect of diet in MDD are advancing and there may be scientifically proven avenues to support standard therapies.
Abstract
BACKGROUND Current treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut-brain-microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study-a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet - is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients. METHODS A total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters. DISCUSSION Microbiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits. TRIAL REGISTRATION NCT03877393 .
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Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial.
Chambers, ES, Byrne, CS, Morrison, DJ, Murphy, KG, Preston, T, Tedford, C, Garcia-Perez, I, Fountana, S, Serrano-Contreras, JI, Holmes, E, et al
Gut. 2019;68(8):1430-1438
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Literature shows that higher intakes of dietary fibre are associated with a reduced risk of type 2 diabetes. The main aim of this study was to elucidate the underlying mechanisms behind improvements in glucose homeostasis following long-term delivery of propionate (a short-chain fatty acid produced by human gut microbiota in response to dietary fibre) to the human colon. The study is a randomised, double-blind, placebo-controlled cross over trial. Fourteen participants randomly received 20 g/day of a low-fermentable fibre control, a high-fermentable fibre control and inulin-propionate ester (IPE) for 42 days each. Results indicate that stool concentrations of short-chain fatty acids were not different following the three supplementation periods. Furthermore, dietary supplementation with 20 g/day IPE promoted no superior impacts on measures of glucose homeostasis compared with inulin (high-fermentable fibre), yet both IPE and inulin improved insulin resistance relative to cellulose (low-fermentable fibre). Authors conclude that manipulating the colonic fermentation profile of a dietary fibre in favour of propionate promotes selective effects on the mechanisms that contribute to metabolic dysregulation.
Abstract
OBJECTIVE To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.
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Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial.
Savino, F, Garro, M, Montanari, P, Galliano, I, Bergallo, M
The Journal of pediatrics. 2018;192:171-177.e1
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Plain language summary
The causes of infant colic are unknown, but growing evidence shows a possible link with the gut microbiome. Increased inflammation has also been found in infants with colic, and this could be linked to dysbiosis. This double-blind, placebo-controlled clinical trial investigated whether supplementation with the probiotic Lactobacillus reuteri (L reuteri) DSM 17938 could reduce the crying time and modify inflammation in a group of infants with colic. Infants enrolled in the trial were less than 12 weeks old, with a healthy birth weight and predominantly breastfed. Infants with colic were given either 5 million colony-forming units (CFU) of L reuteri DSM 17938 or a placebo daily for 1 month. Crying times were significantly shortened among infants with colic given the probiotic, whilst the concentration of transcription factors for cells that help to regulate the immune system increased significantly. Infants treated with the probiotic showed an increase in the percentage of Lactobacillus and a decrease in the inflammatory marker faecal calprotectin. The authors concluded that their findings support the hypothesis that dysbiosis and inflammation may contribute to the onset of infant colic.
Abstract
OBJECTIVES To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic. STUDY DESIGN A double-blind, placebo-controlled randomized trial was conducted in primary care in Torino from August 1, 2015 to September 30, 2016. Patients suffering from infantile colic were randomly assigned to receive daily oral L reuteri (1 × 108 colony forming unit) or placebo for 1 month. Daily crying times were recorded in a structured diary. FOXP3 and RORγ messenger RNA in the peripheral blood was assessed with real-time TaqMan reverse transcription polymerase chain reaction. Gut microbiota and fecal calprotectin were evaluated. RESULTS After infants with colic were supplemented with L reuteri DSM 17938 for 30 days, crying times were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (74.67 ± 25.04 [IQR = 79] minutes /day vs 147.85 [IQR = 135] minutes /day [P = .001]). The FOXP3 concentration increased significantly (P = .009), resulting in decreased RORγ/FOXP3 ratios: 0.61 (IQR = 0.60) at day 0 and 0.48 (IQR = 0.28) at day 30 (P = .028). Furthermore, the probiotic increased the percentage of Lactobacillus (P = .049) and decreased fecal calprotectin (P = .0001). CONCLUSIONS Infants with colic treated with L reuteri for 30 days had a significantly decreased crying time and an increased FOXP3 concentration, resulting in a decreased RORγ/FOXP3 ratio. The treatment reduced fecal calprotectin. TRIAL REGISTRATION ClinicalTrials.gov: NCT00893711.