Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota

Spitzer, Sonia; Tkacz, Andrzej; Savignac, Hélène M.; Cooper, Matthew J.; Giallourou, Natasa; Mann, Edward O.; Bannerman, David M.; Swann, Jonathan R.; Anthony, Daniel C.; Poole, Philip S.; Burnet, Philip W. J.

doi:10.1016/j.isci.2021.103113

Cited by 10 publications

(7 citation statements)

References 69 publications

(77 reference statements)

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“…Interestingly, this effect was only observed if the rats were supplemented prior to weaning, and not when supplemented in adulthood, which suggests that the anxiolytic effects of GOS supplementation in unchallenged animals may depend on the modulation of brain function during a specific neurodevelopmental window. No overall effect of postnatal prebiotic supplementation was observed on the gut microbiome in any age group, although GOS supplementation was found to modify the relationship between branched-chain amino acid levels and age in the hippocampus [91]. Overall, there is substantial preclinical evidence to support a neuromodulatory effect of prebiotics at both juvenile and adult timepoints, despite conflicting evidence in some cases.…”

Section: Prebiotics Modulate Brain Function and Behaviour In Animal M...mentioning

confidence: 85%

“…This included reduced anxiety and depressive-like behaviour [90] and an increased rate of spatial learning in the Morris water maze which was independent of early life stress [89]. Lastly, postnatal supplementation of rats with GOS has been shown to reduce anxiety-like behaviour in the EPM at juvenile (3-week-old), adolescent (8-week-old), and adult (4-6-month-old) timepoints [91]. Interestingly, this effect was only observed if the rats were supplemented prior to weaning, and not when supplemented in adulthood, which suggests that the anxiolytic effects of GOS supplementation in unchallenged animals may depend on the modulation of brain function during a specific neurodevelopmental window.…”

Section: Prebiotics Modulate Brain Function and Behaviour In Animal M...mentioning

confidence: 95%

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Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Radford-Smith

Anthony

2023

Nutrients

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Emerging evidence demonstrates that alterations to the gut microbiota can affect mood, suggesting that the microbiota–gut–brain (MGB) axis contributes to the pathogenesis of depression. Many of these pathways overlap with the way in which the gut microbiota are thought to contribute to metabolic disease progression and obesity. In rodents, prebiotics and probiotics have been shown to modulate the composition and function of the gut microbiota. Together with germ-free rodent models, probiotics have provided compelling evidence for a causal relationship between microbes, microbial metabolites, and altered neurochemical signalling and inflammatory pathways in the brain. In humans, probiotic supplementation has demonstrated modest antidepressant effects in individuals with depressive symptoms, though more studies in clinically relevant populations are needed. This review critically discusses the role of the MGB axis in depression pathophysiology, integrating preclinical and clinical evidence, as well as the putative routes of communication between the microbiota–gut interface and the brain. A critical overview of the current approaches to investigating microbiome changes in depression is provided. To effectively translate preclinical breakthroughs in MGB axis research into novel therapies, rigorous placebo-controlled trials alongside a mechanistic and biochemical understanding of prebiotic and probiotic action are required from future research.

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Section: Prebiotics Modulate Brain Function and Behaviour In Animal M...mentioning

confidence: 85%

Section: Prebiotics Modulate Brain Function and Behaviour In Animal M...mentioning

confidence: 95%

Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Radford-Smith

Anthony

2023

Nutrients

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“…We did not report significant effects of PF administration during lactation on body weight or intestinal morphology in the PNGR and CTRL groups. Similarly, other studies investigating the impacts of postnatal supplementation with different prebiotic compounds in rodents failed to induce significant body weight changes during lactation or at weaning [ 35 , 36 ]. Although the impact of prebiotic supplementation on intestinal microbiota colonization remains undeniable in the case of postnatal supplementation, the results can vary widely between studies [ 19 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prebiotic Supplementation during Lactation Affects Microbial Colonization in Postnatal-Growth-Restricted Mice

et al. 2023

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Background: An inadequate perinatal nutritional environment can alter the maturation of the intestinal barrier and promote long-term pathologies such as metabolic syndrome or chronic intestinal diseases. The intestinal microbiota seems to play a determining role in the development of the intestinal barrier. In the present study, we investigated the impact of consuming an early postnatal prebiotic fiber (PF) on growth, intestinal morphology and the microbiota at weaning in postnatal-growth-restricted mice (PNGR). Methods: Large litters (15 pups/mother) were generated from FVB/NRj mice to induce PNGR at postnatal day 4 (PN4) and compared to control litters (CTRL, 8 pups/mother). PF (a resistant dextrin) or water was orally administered once daily to the pups from PN8 to PN20 (3.5 g/kg/day). Intestinal morphology was evaluated at weaning (PN21) using the ileum and colon. Microbial colonization and short-chain fatty acid (SCFA) production were investigated using fecal and cecal contents. Results: At weaning, the PNGR mice showed decreased body weight and ileal crypt depth compared to the CTRL. The PNGR microbiota was associated with decreased proportions of the Lachnospiraceae and Oscillospiraceae families and the presence of the Akkermansia family and Enterococcus genus compared to the CTRL pups. The propionate concentrations were also increased with PNGR. While PF supplementation did not impact intestinal morphology in the PNGR pups, the proportions of the Bacteroides and Parabacteroides genera were enriched, but the proportion of the Proteobacteria phylum was reduced. In the CTRL pups, the Akkermansia genus (Verrucomicrobiota phylum) was present in the PF-supplemented CTRL pups compared to the water-supplemented ones. Conclusions: PNGR alters intestinal crypt maturation in the ileum at weaning and gut microbiota colonization. Our data support the notion that PF supplementation might improve gut microbiota establishment during the early postnatal period.

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“…In particular, the bidirectional interplay between the gut microbiota and mental health, a pathway facilitated by the gut-brain axis and the vagus nerve (Appleton, 2018; Minichino et al, 2023; Radford-Smith et al, 2022; Safadi et al, 2022). The interplay occurs through production and metabolism of gut microbial metabolites, namely short-chain fatty acids and neurotrophic factors which cumulatively lead to regulation of brain-based processes such as regulation of the hypothalamic-pituitary axis, central and autonomic nervous systems (Bear et al, 2021; Clapp et al, 2017; Sarkar et al, 2016, 2020; Spitzer et al, 2021). Prior literature has also associated gut microbiota disturbances with metabolic dysfunction, namely through improper absorption, digestion, and regulation of hormones (Aoun et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The atypical antipsychotic lurasidone positively modulates the gut microbiota in rats: A comparative study to olanzapine

Kamath,

Hunter,

Collins

et al. 2024

Preprint

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Background and PurposeAntipsychotics like olanzapine are associated with significant metabolic dysfunction, attributable to gut microbiota dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiota has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting, with most reports observing weight loss rather than gain. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiota to explore the hypothesis of “gut neutrality” for lurasidone exposure.Experimental ApproachUsing a Sprague-Dawley rat model, the impact of olanzapine and lurasidone administration on the gut microbiota was explored. Faecal and blood samples were collected weekly over a 21-day period to analyse changes to the gut microbiota and related metabolic markers.Key ResultsLurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating gut microbiota through increases in mean OTUs (+50 OTUs) and alpha diversity (+0.5 increase in Shannon’s index). This novel finding suggests an underlying mechanism for lurasidone’s metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs (−75 OTUs) and substantial compositional variation, suggesting a decrease in microbial richness. Microbiota alterations correlated with metabolic dysfunction, evidenced through a statistically significant 30% increase in weight gain, increase in pro-inflammatory cytokine expression, and increase in blood triglycerides and glycaemic levels.Conclusion and ImplicationsThe study challenges the notion that all antipsychotics disrupt the gut microbiota similarly and highlights the potential benefits of gut positive or neutral antipsychotics like lurasidone in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia.Bullet point summary-What is already known:Olanzapine induces weight gain by disrupting the gut microbiome.The impact of lurasidone on the gut microbiome is unknown and weight gaining propensities unclear.-What this study adds:Lurasidone positively modulates gut microbiota through enhancement of microbial diversity and richness.Potential mechanisms underlying lurasidone’s weight and metabolic neutrality are elucidated.-Clinical significance:Gut neutral antipsychotics like lurasidone could be favourable alternatives for patients unable to tolerate olanzapine.Personalised treatment for schizophrenia considering individual sensitivities to metabolic effects is emphasised.

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Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota

Cited by 10 publications

References 69 publications

Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Prebiotic Supplementation during Lactation Affects Microbial Colonization in Postnatal-Growth-Restricted Mice

The atypical antipsychotic lurasidone positively modulates the gut microbiota in rats: A comparative study to olanzapine

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