The microbiota drives diurnal rhythms in tryptophan metabolism in the stressed gut.

Chronic stress disrupts microbiota-gut-brain axis function and is associated with altered tryptophan metabolism, impaired gut barrier function, and disrupted diurnal rhythms. However, little is known about the effects of acute stress on the gut and how it is influenced by diurnal physiology. Here, we used germ-free and antibiotic-depleted mice to understand how microbiota-dependent oscillations in tryptophan metabolism would alter gut barrier function at baseline and in response to an acute stressor. Cecal metabolomics identified tryptophan metabolism as most responsive to a 15-min acute stressor, while shotgun metagenomics revealed that most bacterial species exhibiting rhythmicity metabolize tryptophan. Our findings highlight that the gastrointestinal response to acute stress is dependent on the time of day and the microbiome, with a signature of stress-induced functional alterations in the ileum and altered tryptophan metabolism in the colon.

The gut microbiome in social anxiety disorder: evidence of altered composition and function.

The microbiome-gut-brain axis plays a role in anxiety, the stress response and social development, and is of growing interest in neuropsychiatric conditions. The gut microbiota shows compositional alterations in a variety of psychiatric disorders including depression, generalised anxiety disorder (GAD), autism spectrum disorder (ASD) and schizophrenia but studies investigating the gut microbiome in social anxiety disorder (SAD) are very limited. Using whole-genome shotgun analysis of 49 faecal samples (31 cases and 18 sex- and age-matched controls), we analysed compositional and functional differences in the gut microbiome of patients with SAD in comparison to healthy controls. Overall microbiota composition, as measured by beta-diversity, was found to be different between the SAD and control groups and several taxonomic differences were seen at a genus- and species-level. The relative abundance of the genera Anaeromassillibacillus and Gordonibacter were elevated in SAD, while Parasuterella was enriched in healthy controls. At a species-level, Anaeromassilibacillus sp An250 was found to be more abundant in SAD patients while Parasutterella excrementihominis was higher in controls. No differences were seen in alpha diversity. In relation to functional differences, the gut metabolic module 'aspartate degradation I' was elevated in SAD patients. In conclusion, the gut microbiome of patients with SAD differs in composition and function to that of healthy controls. Larger, longitudinal studies are warranted to validate these preliminary results and explore the clinical implications of these microbiome changes.

The Microbiome-Gut-Brain axis regulates social cognition & craving in young binge drinkers.

BACKGROUND: Binge drinking is the consumption of an excessive amount of alcohol in a short period of time. This pattern of consumption is highly prevalent during the crucial developmental period of adolescence. Recently, the severity of alcohol use disorders (AUDs) has been linked with microbiome alterations suggesting a role for the gut microbiome in its development. Furthermore, a strong link has emerged too between microbiome composition and socio-emotional functioning across different disorders including AUD. The aim of this study was to investigate the potential link (and its predictive value) between alcohol-related altered microbial profile, social cognition, impulsivity and craving. METHODS: Young people (N = 71) aged 18-25 reported their alcohol use and underwent a neuropsychological evaluation. Craving was measured at baseline and three months later. Diet was controlled for. Blood, saliva and hair samples were taken for inflammatory, kynurenine and cortisol analysis. Stool samples were provided for shotgun metagenomic sequencing and short-chain fatty acids (SCFAs) were measured. FINDINGS: Binge drinking was associated with distinct microbiome alterations and emotional recognition difficulties. Associations were found for several microbiome species with emotional processing and impulsivity. Craving showed a strong link with alterations in microbiome composition and neuroactive potential over time. INTERPRETATION: In conclusion, this research demonstrates alterations in the gut microbiome of young binge drinkers (BDs) and identifies early biomarkers of craving. Associations between emotional processing and microbiome composition further support the growing literature on the gut microbiome as a regulator of social cognition. These findings are of relevance for new gut-derived interventions directed at improving early alcohol-related alterations during the vulnerability period of adolescence. FUNDING: C.C. and R.G-C. received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 754535. APC Microbiome Ireland is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan [grant no. SFI/12/RC/2273_P2]. J.F.C has research support from Cremo, Pharmavite, DuPont and Nutricia. He has spoken at meetings sponsored by food and pharmaceutical companies. G.C. has received honoraria from Janssen, Probi, and Apsen as an invited speaker; is in receipt of research funding from Pharmavite, Fonterra, Nestle and Reckitt; and is a paid consultant for Yakult, Zentiva and Heel pharmaceuticals. All the authors declare no competing interests.

Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population.

The impact of diet on the microbiota composition and the role of diet in supporting optimal mental health have received much attention in the last decade. However, whether whole dietary approaches can exert psychobiotic effects is largely understudied. Thus, we investigated the influence of a psychobiotic diet (high in prebiotic and fermented foods) on the microbial profile and function as well as on mental health outcomes in a healthy human population. Forty-five adults were randomized into either a psychobiotic (n = 24) or control (n = 21) diet for 4 weeks. Fecal microbiota composition and function was characterized using shotgun sequencing. Stress, overall health and diet were assessed using validated questionnaires. Metabolic profiling of plasma, urine and fecal samples was performed. Intervention with a psychobiotic diet resulted in reductions of perceived stress (32% in diet vs. 17% in control group), but not between groups. Similarly, biological marker of stress were not affected. Additionally, higher adherence to the diet resulted in stronger decreases in perceived stress. While the dietary intervention elicited only subtle changes in microbial composition and function, significant changes in the level of 40 specific fecal lipids and urinary tryptophan metabolites were observed. Lastly, microbial volatility was linked to greater changes in perceived stress scores in those on the psychobiotic diet. These results highlight that dietary approaches can be used to reduce perceived stress in a human cohort. Using microbiota-targeted diets to positively modulate gut-brain communication holds possibilities for the reduction of stress and stress-associated disorders, but additional research is warranted to investigate underlying mechanisms, including the role of the microbiota.

Impact of Food Origin Lactiplantibacillus plantarum Strains on the Human Intestinal Microbiota in an in vitro System.

We have previously isolated and characterized food-dwelling strains of Lactiplantibacillus (Lpb.) plantarum that are consumed naturally as part of the microbiota of table olives and raw milk cheeses. Despite being consumed at relatively high levels, the impact of such strains on the human gut microbiota is currently unclear. In the current study we evaluated the potential impact of food-dominant Lpb. plantarum strains on the human gut microbiota using a continuous fecal fermentation system. Daily inoculation of Lpb. plantarum strains led to significant, detectable levels in the fecal fermentation system. We examined the impact of the presence of Lpb. plantarum on the microbiota derived from two separate donors. For one donor, Lpb. plantarum increased alpha diversity and beta diversity. This was reflected in significant alterations in abundance of the unclassified genera, dominated by Enterobacteriaceae_unclass and Ruminococcaceae_unclass. The microbiota of the other donor was relatively unaffected following introduction of the Lpb. plantarum strains. Overall, the work describes the response of the human microbiota to the introduction of high levels of food-dominant Lpb. plantarum strains and indicates that the response may reflect interindividual differences between donor samples.

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner.

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc-/-) and their wild type (Hdc+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc-/- and Hdc+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.

Low-Molecular-Weight Seaweed-Derived Polysaccharides Lead to Increased Faecal Bulk but Do Not Alter Human Gut Health Markers.

Seaweeds are potentially sustainable crops and are receiving significant interest because of their rich bioactive compound content; including fatty acids, polyphenols, carotenoids, and complex polysaccharides. However, there is little information on the in vivo effects on gut health of the polysaccharides and their low-molecular-weight derivatives. Herein, we describe the first investigation into the prebiotic potential of low-molecular-weight polysaccharides (LMWPs) derived from alginate and agar in order to validate their in vivo efficacy. We conducted a randomized; placebo-controlled trial testing the impact of alginate and agar LWMPs on faecal weight and other markers of gut health and on composition of gut microbiota. We show that these LMWPs led to significantly increased faecal bulk (20-30%). Analysis of gut microbiome composition by sequencing indicated no significant changes attributable to treatment at the phylum and family level, although FISH analysis showed an increase in Faecalibacterium prausnitzii in subjects consuming agar LMWP. Sequence analysis of gut bacteria corroborated with the FISH data, indicating that alginate and agar LWMPs do not alter human gut microbiome health markers. Crucially, our findings suggest an urgent need for robust and rigorous human in vivo testing-in particular, using refined seaweed extracts.

Metagenomic analysis of mother-infant gut microbiome reveals global distinct and shared microbial signatures.

Emerging evidence indicates maternal microbiota as one major reservoir for pioneering microbes in infants. However, the global distinct and identical features of mother-infant gut microbiota at various taxonomic resolutions and metabolic functions across cohorts and potential of infant microbial prediction based on their paired mother's gut microbiota remain unclear. Here, we analyzed 376 mother-infant dyads (468 mother and 1024 infant samples) of eight studies from six countries and observed higher diversity at species and strain levels in maternal gut microbiota but not their metabolic functions. A number of 290 species were shared in at least one mother-infant dyad, with 26 species (five at strain level) observed across cohorts. The profile of mother-infant shared species and strains was further influenced by delivery mode and feeding regimen. The mother-sourced species in infants exhibited similar strain heterogeneity but more metabolic functions compared to other-sourced species, suggesting the comparable stability and fitness of shared and non-shared species and the potential role of shared species in the early gut microbial community, respectively. Predictive models showed moderate performance accuracy for shared species and strains occurrences in infants. These generalized mother-infant shared species and strains may be considered as the primary targets for future work toward infant microbiome development and probiotics exploration.

Extraction and characterisation of arabinoxylan from brewers spent grain and investigation of microbiome modulation potential.

PURPOSE: Brewers' spent grain (BSG) represents the largest by-product of the brewing industry. Its utilisation as an animal feed has become less practical today; however, its high fibre and protein content make it a promising untapped resource for human nutrition. BSG contains mainly insoluble fibre. This fibre, along with protein, is trapped with the complex lignocellulosic cell structure and must be solubilised to release components which may be beneficial to health through modulation of the gut microbiota. METHODS: In this study, the application of a simultaneous saccharification and fermentation process for the extraction and solubilisation of arabinoxylan from BSG is demonstrated. RESULTS: Processing of the BSG was varied to modulate the physicochemical and molecular characteristic of the released arabinoxylan. The maximum level of arabinoxylan solubilisation achieved was approximately 21%, compared to the unprocessed BSG which contained no soluble arabinoxylan (AX). Concentration of the solubilised material produced a sample containing 99% soluble AX. Samples were investigated for their microbiome modulating capacity in in-vitro faecal fermentation trials. Many samples promoted increased Lactobacillus levels (approx. twofold). One sample that contained the highest level of soluble AX was shown to be bifidogenic, increasing the levels of this genus approx. 3.5-fold as well as acetate (p = 0.018) and propionate (p < 0.001) production. CONCLUSION: The findings indicate that AX extracted from BSG has prebiotic potential. The demonstration that BSG is a source of functional fibre is a promising step towards the application of this brewing side-stream as a functional food ingredient for human nutrition.

The gut microbiome influences the bioavailability of olanzapine in rats.

BACKGROUND: The role of the gut microbiome in the biotransformation of drugs has recently come under scrutiny. It remains unclear whether the gut microbiome directly influences the extent of drug absorbed after oral administration and thus potentially alters clinical pharmacokinetics. METHODS: In this study, we evaluated whether changes in the gut microbiota of male Sprague Dawley rats, as a result of either antibiotic or probiotic administration, influenced the oral bioavailability of two commonly prescribed antipsychotics, olanzapine and risperidone. FINDINGS: The bioavailability of olanzapine, was significantly increased (1.8-fold) in rats that had undergone antibiotic-induced depletion of gut microbiota, whereas the bioavailability of risperidone was unchanged. There was no direct effect of microbiota depletion on the expression of major CYP450 enzymes involved in the metabolism of either drug. However, the expression of UGT1A3 in the duodenum was significantly downregulated. The reduction in faecal enzymatic activity, observed during and after antibiotic administration, did not alter the ex vivo metabolism of olanzapine or risperidone. The relative abundance of Alistipes significantly correlated with the AUC of olanzapine but not risperidone. INTERPRETATION: Alistipes may play a role in the observed alterations in olanzapine pharmacokinetics. The gut microbiome might be an important variable determining the systemic bioavailability of orally administered olanzapine. Additional research exploring the potential implication of the gut microbiota on the clinical pharmacokinetics of olanzapine in humans is warranted. FUNDING: This research is supported by APC Microbiome Ireland, a research centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (grant no. 12/RC/2273 P2) and by Nature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891).

A specific dietary fibre supplementation improves cognitive performance-an exploratory randomised, placebo-controlled, crossover study.

RATIONALE: The impact of the microbiota on the gut-brain axis is increasingly appreciated. A growing body of literature demonstrates that use of dietary fibre and prebiotics can manipulate the microbiota and affect host health. However, the influence on cognition and acute stress response is less well understood. OBJECTIVES: The objective of this study was to investigate the efficacy of a dietary fibre, polydextrose (PDX), in improving cognitive performance and acute stress responses through manipulation of the gut microbiota in a healthy population. METHODS: In this double-blind, randomised, placebo-controlled, crossover design study, 18 healthy female participants received 12.5 g Litesse®Ultra (> 90% PDX polymer) or maltodextrin for 4 weeks. Cognitive performance, mood, acute stress responses, microbiota composition, and inflammatory markers were assessed pre- and post-intervention. RESULTS: PDX improved cognitive flexibility as evidenced by the decrease in the number of errors made in the Intra-Extra Dimensional Set Shift (IED) task. A better performance in sustained attention was observed through higher number of correct responses and rejections in the Rapid Visual Information Processing (RVP) task. Although there was no change in microbial diversity, abundance of Ruminiclostridium 5 significantly increased after PDX supplementation compared with placebo. PDX supplementation attenuated the increase of adhesion receptor CD62L on classical monocytes observed in the placebo group. CONCLUSIONS: Supplementation with the PDX resulted in a modest improvement in cognitive performance. The results indicate that PDX could benefit gut-to-brain communication and modulate behavioural responses.

Microbiome Transfer Partly Overrides Lack of IL-1RI Signaling to Alter Hepatic but not Adipose Tissue Phenotype and Lipid Handling following a High-Fat Diet Challenge.

SCOPE: IL-1RI-mediated inflammatory signaling alters metabolic tissue responses to dietary challenges (e.g., high-fat diet [HFD]). Recent work suggests that metabolic phenotype is transferrable between mice in a shared living environment (i.e., co-housing) due to gut microbiome exchange. The authors examine whether the metabolic phenotype of IL-1RI-/- mice fed HFD or low-fat diet (LFD) could be transferred to wild-type (WT) mice through gut microbiome exchange facilitated by co-housing. METHODS AND RESULTS: Male WT (C57BL/J6) and IL-1RI-/- mice are fed HFD (45% kcal) or LFD (10% kcal) for 24 weeks and housed i) by genotype (single-housed) or ii) with members of the other genotype in a shared microbial environment (co-housed). The IL-1RI-/-  gut microbiome is dominant to WT, meaning that co-housed WT mice adopted the IL-1RI-/- microbiota profile. This is concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy, and hyperinsulinemia in co-housed WT mice, compared to single-housed counterparts. These effects are most evident following HFD. Primary features of microbiome differences are Lachnospiraceae and Ruminococcaceae (known producers of SCFA). CONCLUSION: Transfer of SCFA-producing microbiota from IL-1RI-/- mice highlights a new connection between diet, inflammatory signaling, and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge.

Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human.

BACKGROUND: The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. METHODS: B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. FINDINGS: B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). INTERPRETATION: This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. FUNDING: This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

Lactobacillus rhamnosus GG soluble mediators ameliorate early life stress-induced visceral hypersensitivity and changes in spinal cord gene expression.

Visceral hypersensitivity is a hallmark of many functional and stress-related gastrointestinal disorders, and there is growing evidence that the gut microbiota may play a role in its pathophysiology. It has previously been shown that early life stress-induced visceral sensitivity is reduced by various probiotic strains of bacteria (including Lactobacillus rhamnosus GG (LGG)) alone or in combination with prebiotic fibres in rat models. However, the exact mechanisms underpinning such effects remain unresolved. Here, we investigated if soluble mediators derived from LGG can mimic the bacteria's effects on visceral hypersensitivity and the microbiota-gut-brain axis. Rats were exposed to maternal separation (MS) from postnatal days 2-12. From weaning onwards both non-separated (NS) and MS offspring were provided drinking water with or without supplementation of standardized preparations of the LGG soluble mediators (LSM). Our results show that MS led to increased visceral sensitivity and exaggerated corticosterone plasma levels following restraint stress in adulthood, and both of these effects were ameliorated through LSM supplementation. Differential regulation of various genes in the spinal cord of MS versus NS rats was observed, 41 of which were reversed by LSM supplementation. At the microbiota composition level MS led to changes in beta diversity and abundance of specific bacteria including parabacteroides, which were ameliorated by LSM. These findings support probiotic soluble mediators as potential interventions in the reduction of symptoms of visceral hypersensitivity.

Future of Probiotics and Prebiotics and the Implications for Early Career Researchers.

The opportunities in the fields of probiotics and prebiotics to a great degree stem from what we can learn about how they influence the microbiota and interact with the host. We discuss recent insights, cutting-edge technologies and controversial results from the perspective of early career researchers innovating in these areas. This perspective emerged from the 2019 meeting of the International Scientific Association for Probiotics and Prebiotics - Student and Fellows Association (ISAPP-SFA). Probiotic and prebiotic research is being driven by genetic characterization and modification of strains, state-of-the-art in vitro, in vivo, and in silico techniques designed to uncover the effects of probiotics and prebiotics on their targets, and metabolomic tools to identify key molecules that mediate benefits on the host. These research tools offer unprecedented insights into the functionality of probiotics and prebiotics in the host ecosystem. Young scientists need to acquire these diverse toolsets, or form inter-connected teams to perform comprehensive experiments and systematic analysis of data. This will be critical to identify microbial structure and co-dependencies at body sites and determine how administered probiotic strains and prebiotic substances influence the host. This and other strategies proposed in this review will pave the way for translating the health benefits observed during research into real-life outcomes. Probiotic strains and prebiotic products can contribute greatly to the amelioration of global issues threatening society. The intent of this article is to provide an early career researcher's perspective on where the biggest opportunities lie to advance science and impact human health.

Recipe for a Healthy Gut: Intake of Unpasteurised Milk Is Associated with Increased Lactobacillus Abundance in the Human Gut Microbiome.

INTRODUCTION: The gut microbiota plays a role in gut-brain communication and can influence psychological functioning. Diet is one of the major determinants of gut microbiota composition. The impact of unpasteurised dairy products on the microbiota is unknown. In this observational study, we investigated the effect of a dietary change involving intake of unpasteurised dairy on gut microbiome composition and psychological status in participants undertaking a residential 12-week cookery course on an organic farm. METHODS: Twenty-four participants completed the study. The majority of food consumed during their stay originated from the organic farm itself and included unpasteurised milk and dairy products. At the beginning and end of the course, participants provided faecal samples and completed self-report questionnaires on a variety of parameters including mood, anxiety and sleep. Nutrient intake was monitored with a food frequency questionnaire. Gut microbiota analysis was performed with 16S rRNA gene sequencing. Additionally, faecal short chain fatty acids (SCFAs) were measured. RESULTS: Relative abundance of the genus Lactobacillus increased significantly between pre- and post-course time points. This increase was associated with participants intake of unpasteurised milk and dairy products. An increase in the faecal SCFA, valerate, was observed along with an increase in the functional richness of the microbiome profile, as determined by measuring the predictive neuroactive potential using a gut-brain module approach. CONCLUSIONS: While concerns in relation to safety need to be considered, intake of unpasteurised milk and dairy products appear to be associated with the growth of the probiotic bacterial genus, Lactobacillus, in the human gut. More research is needed on the effect of dietary changes on gut microbiome composition, in particular in relation to the promotion of bacterial genera, such as Lactobacillus, which are recognised as being beneficial for a range of physical and mental health outcomes.

Effects of a polysaccharide-rich extract derived from Irish-sourced Laminaria digitata on the composition and metabolic activity of the human gut microbiota using an in vitro colonic model.

BACKGROUND: Brown seaweeds are known to be a rich source of fiber with the presence of several non-digestible polysaccharides including laminarin, fucoidan and alginate. These individual polysaccharides have previously been shown to favorably alter the gut microbiota composition and activity albeit the effect of the collective brown seaweed fiber component on the microbiota remains to be determined. METHODS: This study investigated the effect of a crude polysaccharide-rich extract obtained from Laminaria digitata (CE) and a depolymerized CE extract (DE) on the gut microbiota composition and metabolism using an in vitro fecal batch culture model though metagenomic compositional analysis using 16S rRNA FLX amplicon pyrosequencing and short-chain fatty acid (SCFA) analysis using GC-FID. RESULTS: Selective culture analysis showed no significant changes in cultured lactobacilli or bifidobacteria between the CE or DE and the cellulose-negative control at any time point measured (0, 5, 10, 24, 36, 48 h). Following metagenomic analysis, the CE and DE significantly altered the relative abundance of several families including Lachnospiraceae and genera including Streptococcus, Ruminococcus and Parabacteroides of human fecal bacterial populations in comparison to cellulose after 24 h. The concentrations of acetic acid, propionic acid, butyric acid and total SCFA were significantly higher for both the CE and DE compared to cellulose after 10, 24, 36 and 48 h fermentation (p < 0.05). Furthermore, the acetate:propionate ratio was significantly reduced (p < 0.05) for both CD and DE following 24, 36 and 48 h fermentation. CONCLUSION: The microbiota-associated metabolic and compositional changes noted provide initial indication of putative beneficial health benefits of L. digitata in vitro; however, research is needed to clarify if L. digitata-derived fiber can favorably alter the gut microbiota and confer health benefits in vivo.

The enduring effects of early-life stress on the microbiota-gut-brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend.

Nutritional interventions targeting the microbiota-gut-brain axis are proposed to modulate stress-induced dysfunction of physiological processes and brain development. Maternal separation (MS) in rats induces long-term alterations to behaviour, pain responses, gut microbiome and brain neurochemistry. In this study, the effects of dietary interventions (milk fat globule membrane [MFGM] and a polydextrose/galacto-oligosaccharide prebiotic blend) were evaluated. Diets were provided from postnatal day 21 to both non-separated and MS offspring. Spatial memory, visceral sensitivity and stress reactivity were assessed in adulthood. Gene transcripts associated with cognition and stress and the caecal microbiota composition were analysed. MS-induced visceral hypersensitivity was ameliorated by MFGM and to greater extent with the combination of MFGM and prebiotic blend. Furthermore, spatial learning and memory were improved by prebiotics and MFGM alone and with the combination. The prebiotic blend and the combination of the prebiotics and MFGM appeared to facilitate return to baseline with regard to HPA axis response to the restraint stress, which can be beneficial in times where coping mechanisms to stressful events are required. Interestingly, the combination of MFGM and prebiotic reduced the long-term impact of MS on a marker of myelination in the prefrontal cortex. MS affected the microbiota at family level only, while MFGM, the prebiotic blend and the combination influenced abundance at family and genus level as well as influencing beta-diversity levels. In conclusion, intervention with MFGM and prebiotic blend significantly impacted the composition of the microbiota as well as ameliorating some of the long-term effects of early-life stress.

Prebiotics from Seaweeds: An Ocean of Opportunity?

Seaweeds are an underexploited and potentially sustainable crop which offer a rich source of bioactive compounds, including novel complex polysaccharides, polyphenols, fatty acids, and carotenoids. The purported efficacies of these phytochemicals have led to potential functional food and nutraceutical applications which aim to protect against cardiometabolic and inflammatory risk factors associated with non-communicable diseases, such as obesity, type 2 diabetes, metabolic syndrome, cardiovascular disease, inflammatory bowel disease, and some cancers. Concurrent understanding that perturbations of gut microbial composition and metabolic function manifest throughout health and disease has led to dietary strategies, such as prebiotics, which exploit the diet-host-microbe paradigm to modulate the gut microbiota, such that host health is maintained or improved. The prebiotic definition was recently updated to "a substrate that is selectively utilised by host microorganisms conferring a health benefit", which, given that previous discussion regarding seaweed prebiotics has focused upon saccharolytic fermentation, an opportunity is presented to explore how non-complex polysaccharide components from seaweeds may be metabolised by host microbial populations to benefit host health. Thus, this review provides an innovative approach to consider how the gut microbiota may utilise seaweed phytochemicals, such as polyphenols, polyunsaturated fatty acids, and carotenoids, and provides an updated discussion regarding the catabolism of seaweed-derived complex polysaccharides with potential prebiotic activity. Additional in vitro screening studies and in vivo animal studies are needed to identify potential prebiotics from seaweeds, alongside untargeted metabolomics to decipher microbial-derived metabolites from seaweeds. Furthermore, controlled human intervention studies with health-related end points to elucidate prebiotic efficacy are required.

Preventing adolescent stress-induced cognitive and microbiome changes by diet.

Psychological stress during adolescence may cause enduring cognitive deficits and anxiety in both humans and animals, accompanied by rearrangement of numerous brain structures and functions. A healthy diet is essential for proper brain development and maintenance of optimal cognitive functions during adulthood. Furthermore, nutritional components profoundly affect the intestinal community of microbes that may affect gut-brain communication. We adopted a relatively mild stress protocol, social instability stress, which when repeatedly administered to juvenile rats modifies cognitive behaviors and plasticity markers in the brain. We then tested the preventive effect of a prolonged diet enriched with the ω-3 polyunsaturated fatty acids eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid and vitamin A. Our findings highlight the beneficial effects of this enriched diet on cognitive memory impairment induced by social instability stress, as stressed rats fed the enriched diet exhibited performance undistinguishable from that of nonstressed rats on both emotional and reference memory tests. Furthermore, in stressed rats, the decline in brain-derived neurotrophic factor expression in the hippocampus and shifts in the microbiota composition were normalized by the enriched diet. The detrimental behavioral and neurochemical effects of adolescent stress, as well as the protective effect of the enriched diet, were maintained throughout adulthood, long after the exposure to the stressful environment was terminated. Taken together, our results strongly suggest a beneficial role of nutritional components in ameliorating stress-related behaviors and associated neurochemical and microbiota changes, opening possible new venues in the field of nutritional neuropsychopharmacology.