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Impact of Blueberry Consumption on the Human Fecal Bileacidome: A Pilot Study of Bile Acid Modulation by Freeze-Dried Blueberry.
Gagnon, W, Garneau, V, Trottier, J, Verreault, M, Couillard, C, Roy, D, Marette, A, Drouin-Chartier, JP, Vohl, MC, Barbier, O
Nutrients. 2022;14(18)
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Primary bile acids (BAs) are made in the liver from cholesterol. They are released into the small intestine, where they aid fat digestion and absorption. Most BAs are reabsorbed from the gut, yet a small amount gets modified by the gut bacteria, forming secondary BAs destined for faecal excretion. Excess secondary BAs have negative health consequences. The different types of primary BAs influence many physiological functions. Such as glucose regulation, fat metabolism and absorption, intestinal inflammation and immunity, as well as gut bacteria diversity. For optimal BA metabolism, they are tightly regulated by the body, as minimal changes in BA pool and composition can have a significant impact on overall health. The composition of the BA pool can be influenced by gut bacteria, metabolic disorders, pathologies of the liver and gut, and diet. Dietary polyphenols, a plant-based compound, have been of particular interest here. This study sought to investigate the impact of supplementary freeze-dried blueberry powder (BBP), a rich polyphenol source, on the faecal BA pool composition in people at risk of metabolic syndrome. For this 11 men and 13 women were supplemented for 8 weeks. When compared to the data before the intervention, no significant changes in total BAs were observed. However, the composition of the BA pool changed leading to the accumulation of particular BAs and a reduction in secondary BA levels. This suggested that the consumption of blueberries can be considered a potential clinical intervention to aid the elimination of toxic secondary BAs. As the mechanisms leading to such modifications and their consequences for human health are complex, the authors advocate for investigation in larger population groups and also alert that such changes may be subject to interindividual variability and health status.
Abstract
Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. In the present study, we analyzed the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk of metabolic syndrome was supplemented with 50 g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled with tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs. post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p = 0.04), glycochenodeoxycholic (p = 0.01), and glycoursodeoxycholic (p = 0.01) acids, as well as a significant reduction (p = 0.03) in the secondary BA levels compared with pre-BBP feces. In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BA elimination.
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The role of gut microbiome in inflammatory skin disorders: A systematic review.
Widhiati, S, Purnomosari, D, Wibawa, T, Soebono, H
Dermatology reports. 2022;14(1):9188
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Gut-skin axis refers to the complex cross-talk between gut bacteria and skin. Although the exact mechanism underlying chronic inflammatory skin conditions is unknown, imbalances in the composition of gut microbes are believed to play a role. Twenty-three studies were included in this systematic review to assess whether gut microbial imbalance may contribute to inflammatory skin conditions such as Psoriasis, Acne Vulgaris, Atopic Dermatitis, and Urticaria. According to this systematic review, immune stimulation, inflammation, and disruption of bacterial composition are common mechanisms in all these skin disorders. A western diet and environmental exposures are found to be contributing to the disruption of bacteria and the pathology of these skin disorders. It has been observed that friendly gut bacteria such as Bifidobacterium are reduced in people with inflammatory skin conditions, whereas elevated levels of pathogenic bacteria such as E. coli and Proteobacteria are present in the gut of patients with inflammatory skin conditions. The abundance of anti-inflammatory bacteria such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Clostridium leptum, Lactobacillus, and Bifidobacterium may protect against inflammatory skin conditions. Further robust studies are required to evaluate the pathogenesis behind inflammatory skin conditions as well as the involvement of gut bacteria in the development and progression of the disease. Healthcare professionals can gain a deeper understanding of gut bacteria that contribute to the pathology of inflammatory diseases as well as how clinically using anti-inflammatory bacterial species may improve the condition of individuals suffering from inflammatory skin conditions.
Abstract
The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.
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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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Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: a prospective cohort study.
Wu, M, Chi, C, Yang, Y, Guo, S, Li, T, Gu, M, Zhang, T, Gao, H, Liu, R, Yin, C
BMC pregnancy and childbirth. 2022;22(1):592
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Subclinical hypothyroidism (SCH) in pregnancy refers to the elevation of thyroid stimulating hormone level with normal free T4 level. One third of women with SCH have been reported to test positive for anti-thyroid peroxidase antibody (TPOAb+). The aim of this study was to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. This study was a nested, prospective observational cohort study. A total of 64 and 68 pregnant women with TPOAb+ and TPOAb negative SCH, respectively, were included in this study. Results showed that women who were diagnosed with TPOAb+ SCH in trimester (T)1 show distinct dynamics of gut microbiota from T2 to T3. Furthermore, changes in the abundances of three types of bacterial species were abnormal in the presence of levothyroxine treatment. Authors conclude that gut microbiota can serve as potential therapeutic targets for TPOAb+ SCH during pregnancy.
Abstract
BACKGROUND Anti-thyroid peroxidase antibody (TPOAb) positivity can contribute to inhibit thyroxine synthesis. Gut microbiota can interact with metabolic or immune diseases. However, dynamics of gut microbiota from the second (T2) to the third trimester (T3) in women with TPOAb-positive/negative subclinical hypothyroidism (TPOAb+/TPOAb- SCH) have not been reported. Therefore, we aimed to evaluate whether gut microbiota can be potential therapeutic targets for managing TPOAb+ SCH. METHODS In this single-center prospective cohort study, we observed gut microbiota dynamics by sequencing 16S rRNA from fecal samples collected in T2 (20-23+ 6 weeks) and T3 (28-33+ 6 weeks). TPOAb+/TPOAb- SCH were stratified depending on whether or not they used levothyroxine (LT4) during the pregnancy (LT4+/LT4-). Microbiome bioinformatics analyses were performed using QIIME2. The linear discriminant analysis effect size (LEfSe) was used for the quantitative analysis of biomarkers. Functional profiling was performed with PICRUSt2. RESULTS Distinct gut microbiota dynamics from T2 to T3 were noted in the TPOAb- (n = 68) and TPOAb+ (n = 64) SCH groups. The TPOAb+ LT4- group was characterized by enriched bacterial amplicon sequence variants (ASVs) of Prevotella in T2 and Bacteria, Lachnospirales, Lachnospiraceae, Blautia, and Agathobacter in T3 and by depleted ASVs of Gammaproteobacteria, Enterobacterales, and Enterobacteriaceae in T2 and Actinobacteriota, Coriobacteriia, Actinobacteria, Coriobacteriales, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, Dorea formicigenerans, and Bifidobacterium longum in T3. The TPOAb+ LT4+ group was characterized by enriched bacterial ASVs of Blautia, Streptococcus salivarius, and Bifidobacterium longum in T3 and by depleted ASVs of Bacteroidota, Bacteroidia, Bacteroidales, and Prevotella in T2 and Agathobacter in T3. Moreover, we identified 53 kinds of metabolic functions that were mainly involved in sugar, lipid, and amino acid metabolism. CONCLUSIONS Our results indicated that low dynamics of gut microbiota composition and high dynamics of its metabolic function from T2 to T3 were associated with TPOAb+ SCH. We concluded that gut microbiota could be new targets for treatment of TPOAb+ SCH during pregnancy. TRIAL REGISTRATION This study was retrospectively registered at the Chinese Clinical Trial Registry (registration number ChiCTR2100047175 ) on June 10, 2021.
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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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The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation.
Rahman, MM, Islam, F, -Or-Rashid, MH, Mamun, AA, Rahaman, MS, Islam, MM, Meem, AFK, Sutradhar, PR, Mitra, S, Mimi, AA, et al
Frontiers in cellular and infection microbiology. 2022;12:903570
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Cardiovascular disease (CVD) accounts for 31% of all-cause mortality worldwide. Irregularities in the composition of intestinal microbial composition, genetic factors, nutrition, metabolic irregularities, and smoking are among the potential causes of CVD. Intestinal permeability and translocation of endotoxins and bacterial metabolites to systemic circulation may trigger an immune response and inflammation, which may increase the risk of CVD. Synthesis of bacterial metabolites such as trimethylamine N-oxide (TMAO) by choline-inducing gut bacteria and reduced consumption of dietary TMAO precursors may elevate the CVD risk. This review explores the latest research on the role of gut microbiota in the development of atherosclerosis and CVD, as well as potential strategies to prevent CVD by targeting TMAO-producing gut bacteria. Elevated levels of TMAO in the bloodstream can lead to the buildup of cholesterol and ultimately result in atherosclerosis. However, consuming probiotics and fibre-rich foods can help regulate gut bacteria, reduce inflammation, and improve lipid profiles, all of which contribute to better cardiovascular health. More future robust studies are required to examine the mechanistic insights and confirm whether TMAO can serve as a biomarker for preventing CVD through the therapeutic modulation of intestinal bacteria.
Abstract
In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.
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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.