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COVID-19: A pandemic that threatens physical and mental health by promoting physical inactivity.
Ever since the outbreak of Coronavirus disease 2019 (COVID-19) in late 2019, it has killed millions of people worldwide. Even people not stricken by this disease are not spared from its negative economic, social, and health-related drawbacks. This commentary provides insight into the potential mechanisms involved in the development of depression and emotional negativity escalating during the current pandemic. In particular, preventive measures of COVID-19, such as staying at home, are sedentarism measures that decrease physical activity. Physical inactivity alters gut microbiome structure in a fashion that promotes gut dysbiosis and flaring of systemic inflammation, leading to the buildup of body fat. Obesity, which contributes to a trail of health-depleting disorders, furthers gut microbial disintegration while fat tissue stimulates the release of cytokines, promotes metabolic resistance, and alters signaling involved in the production of antioxidants. As a result, the body gets flooded by toxic molecules such pro-inflammatory mediators, free radicals, and advanced glycation end products. These toxic molecules alter cellular function in all body tissues, including those of the brain. Neuroinflammation is associated with progressive declines in cognitive and motor functions along with dysregulation in emotions. Counteracting the sedentarism enforced by the COVID-19 pandemic through the participation in suitable indoors activities and the intake of healthy food is likely to protect against or revert physiological impairments that may affect people retreating to their homes during the current crisis, eventually restoring physical and mental health.
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Synergistic Neuroimmune Modulation by Cannabidiol and Probiotics for Therapeutic Advancement in CNS Disorders: A Systematic Review.
INTRODUCTION: The gut-brain axis (GBA) is a complex, bidirectional communication network connecting the gastrointestinal tract and central nervous system. Cannabidiol (CBD) and probiotics have shown promising neuroprotective, anti-inflammatory, and immunomodulatory effects. However, the synergistic potential of these agents on the GBA has not been fully explored. METHODS: A systematic review of recent preclinical and clinical studies was conducted using databases such as PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. The review focused on the individual and combined effects of CBD and probiotics on gut microbiota composition, neuroinflammation, neurotransmitter modulation, and immune signalling. Mechanistic insights involving the endocannabinoid system and microbiome-derived metabolites were also analyzed. RESULTS: Evidence suggests that both CBD and probiotics can enhance gut microbial diversity, regulate pro-inflammatory cytokines, and increase neuroactive metabolites like serotonin and short-chain fatty acids. These effects may improve vagus nerve activity and gut-brain communication, indicating therapeutic potential for managing anxiety, depression, and neurodegenerative conditions. However, human studies remain limited in scale and duration. DISCUSSION: The observed benefits of CBD and probiotics suggest a synergistic mechanism through gut-brain axis modulation, addressing both neurological and immunological pathways. While animal studies are promising, translation to clinical practice requires further evidence. CONCLUSION: CBD and probiotics represent a novel combinatorial approach for managing central nervous system disorders through GBA modulation. Future clinical trials should establish optimal dosing, long-term safety, and therapeutic efficacy to validate their use in neuroimmune conditions.
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Evidence for Brain-To-Gut and Gut-To-Brain Pathways in Primary Care Patients With Disorders of Gut-Brain Interaction, Inflammatory Bowel Disease and Gastroesophageal Reflux Disease.
BACKGROUND: Apart from disorders of gut-brain interaction (DGBI), little data exist on the magnitude of the brain-to-gut pathway in other chronic gastrointestinal conditions such as gastroesophageal reflux disease (GERD) or inflammatory bowel disease (IBD) and what factors modify order of diagnosis. We aimed to determine the proportion of patients who received a diagnosis of a DGBI, GERD, or IBD prior to a new psychological diagnosis (gut-to-brain), and vice versa (brain-to-gut), and whether specific factors moderate the order of diagnosis. METHOD: Data was collected from a retrospective study of 1,129,104 patients attending general practices in the United Kingdom. Patients diagnosed with DGBI, GERD, or IBD and a psychological disorder (anxiety and/or depression) were included (excluding those with other organic GI disease). Information on which diagnosis appeared first was recorded. Multiple logistic regression was performed to compare a diagnosis of a DGBI, GERD, or IBD first versus a psychological diagnosis first on sociodemographic factors, medical conditions, and medication usage. KEY RESULTS: Just over half of patients were diagnosed with a psychological condition first versus after for IBS (53.9%) and ulcerative colitis (55.6%). This proportion was higher for FD (61.5%) and GERD (64.2%) but lower for Crohn's disease (45.7%). In a multivariate model, being female (OR = 1.37, 95% CI 1.25, 1.49), prior PPI (OR = 9.17, 95% CI 8.4, 10.0), antibiotic (OR = 2.54, 95% CI 2.29, 2.81) and NSAID use (OR = 1.29, 95% CI 1.18, 1.42), and prior gastroenteritis (OR = 2.19, 95% CI, 1.79, 2.67) were significant predictors for being diagnosed with GERD first. Similar results were found for DGBI. CONCLUSIONS & INFERENCES: Prior medication usage and gastroenteritis may play a role in generating gut-to-brain pathway disturbances.
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Pubertal consumption of R. badensis subspecies acadiensis modulates LPS-induced immune responses and gut microbiome dysbiosis in a sex-specific manner.
Puberty is a critical period of development characterized by significant brain remodeling and increased vulnerability to immune challenges. Exposure to an immune challenge such as LPS during puberty can result in inflammation and gut dysbiosis which may lead to altered brain functioning and psychiatric illnesses later in life. However, treatment with probiotics during puberty has been found to mitigate LPS-induced peripheral and central inflammation, prevent LPS-induced changes to the gut microbiota and protect against enduring behavioural disorders in a sex-specific manner. Recent findings from our laboratory revealed that pubertal R. badensis subspecies acadiensis (R. badensis subsp. acadiensis) treatment prevents LPS-induced depression-like behavior and alterations in 5HT1A receptor expression in a sex-specific manner. However, the underlying mechanism remains unclear. Thus, the aim of this study was to gain mechanistic insights and to investigate the ability of R. badensis subsp. acadiensis consumption during puberty to mitigate the effects of LPS treatment on the immune system and the gut microbiome. Our results revealed that pubertal treatment with R. badensis subsp. acadiensis reduced sickness behaviors in females more than males in a time-specific manner. It also mitigated LPS-induced increases in pro-inflammatory cytokines in the blood and in TNFα mRNA expression in the prefrontal cortex and the hippocampus of female mice. There were sex-dependent differences in microbiome composition that persisted after LPS injection or R. badensis subsp. acadiensis consumption. R. badensis subsp. acadiensis had greater impact on the microbiota of male mice but female microbiota's were more responsive to LPS treatment. This suggested that female mice microbiota's may be more prone to modulation by this probiotic. These findings emphasize the sex-specific effects of probiotic use during puberty on the structure of the gut microbiome and the immune system and highlight the critical role of gut colonization with probiotics during adolescence on immunomodulation and prevention of the enduring effects of infections.
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Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes.
The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars' attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota-CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.
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Retraction Note: Gut Microbiome Dysbiosis and Depression: A Comprehensive Review.
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Experiences of discrimination are associated with microbiome and transcriptome alterations in the gut.
BACKGROUND: Discrimination is a recognized psychosocial stressor that has been linked to various negative health outcomes. This study explored the impact of discrimination on gut health, specifically focusing on microbiome changes, predicted metagenomic differences, transcriptomic profiles, and the potential for using a multi-omic approach to predict discrimination to identify discrimination status for an individual. Methods: We conducted a comprehensive investigation involving male and premenopausal female participants, using the Everyday Discrimination Scale to classify them into either high or low discrimination. Multiple questionnaires were administered to evaluate participants' physiological, psychological, and perceived stressors. Two diet questionnaires were also administered. Stool samples were collected for microbiome analysis and RNA sequencing. Microbial composition changes were analyzed using the Shannon index and Chao1 richness estimator for alpha diversity and the Aitchison distance metric for beta diversity. Differential abundance was evaluated using MaAsLin2, followed by metatranscriptomics sequencing and annotation. A multi-omic approach utilizing random forest was used to assess the predictability of discrimination. RESULTS: The study results showed that high discrimination was linked to higher gut microbiome species richness (Chao1, p = 0.02) and significant beta diversity differences (p = 0.04). Prevotella and Ruminococcaceae were both less abundant in the high discrimination group. High discrimination participants also reported higher levels of depression, anxiety, perceived stress, early life adversity, visceral sensitivity, and neuroticism than those in the low discrimination group. Gene expression analysis revealed distinctive patterns, with significant changes in genes associated with environmental sensing (two-component system) and metabolic pathways. In a plot comparing gene transcription to DNA content, certain genes showed higher expression levels in participants who experienced both high and low levels of discrimination. Our random forest classifier demonstrated the capability to accurately differentiate individuals with high and low discrimination in our training cohort (AUC = 0.91). CONCLUSION: These findings illuminate the substantial impact of discrimination on gut health, encompassing microbiome composition, gene expression, and functional pathways. These findings suggest that discrimination is associated with internal biological changes that can be associated with negative health outcomes, opening research to examine novel pathways that can be used to mitigate the negative health effects of discrimination.
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Effects of Six Sequential Charged Particle Beams on Behavioral and Cognitive Performance in B6D2F1 Female and Male Mice.
The radiation environment astronauts are exposed to in deep space includes galactic cosmic radiation (GCR) with different proportions of all naturally occurring ions. To assist NASA with assessment of risk to the brain following exposure to a mixture of ions broadly representative of the GCR, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice two months following rapidly delivered, sequential 6 beam irradiation with protons (1 GeV, LET = 0.24 keV, 50%), 4He ions (250 MeV/n, LET = 1.6 keV/μm, 20%), 16O ions (250 MeV/n, LET = 25 keV/μm 7.5%), 28Si ions (263 MeV/n, LET = 78 keV/μm, 7.5%), 48Ti ions (1 GeV/n, LET = 107 keV/μm, 7.5%), and 56Fe ions (1 GeV/n, LET = 151 keV/μm, 7.5%) at 0, 25, 50, or 200 cGy) at 4-6 months of age. When the activity over 3 days of open field habituation was analyzed in female mice, those irradiated with 50 cGy moved less and spent less time in the center than sham-irradiated mice. Sham-irradiated female mice and those irradiated with 25 cGy showed object recognition. However, female mice exposed to 50 or 200 cGy did not show object recognition. When fear memory was assessed in passive avoidance tests, sham-irradiated mice and mice irradiated with 25 cGy showed memory retention while mice exposed to 50 or 200 cGy did not. The effects of radiation passive avoidance memory retention were not sex-dependent. There was no effect of radiation on depressive-like behavior in the forced swim test. There was a trend toward an effect of radiation on BDNF levels in the cortex of males, but not for females, with higher levels in male mice irradiated with 50 cGy than sham-irradiated. Finally, sequential 6-ion irradiation impacted the composition of the gut microbiome in a sex-dependent fashion. Taxa were uncovered whose relative abundance in the gut was associated with the radiation dose received. Thus, exposure to sequential six-beam irradiation significantly affects behavioral and cognitive performance and the gut microbiome.
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In Conversation with John Cryan.
John F. Cryan is Chair of the Department of Anatomy and Neuroscience, Principal Investigator in the APC Microbiome Ireland Institute and Vice President for Research and Innovation at University College of Cork, Ireland. He obtained his bachelor's and doctoral degrees (in Biochemistry and Pharmacology, respectively) from the University of Galway and undertook postdoctoral research experience in the USA, at the University of Pennsylvania and The Scripps Research Institute. He was also a visiting fellow at the Department of Psychiatry, University of Melbourne, for a couple of years post-PhD. In 2002, John took up a position in industry as a laboratory head at the Novartis Institutes for BioMedical Research in Basel, Switzerland. After a 4-year stint at Novartis, he returned to academia in late 2005 as a Lecturer and then Senior Lecturer in Pharmacology at University College Cork (UCC). The Cryan lab now focuses on determining the impact of the gut microbiota on the human brain and behaviour, with a particular interest in the brain-gut-microbiome axis in the context of depression. John has published more than 600 peer-reviewed papers and has received many honours and accolades in recognition of his contributions to neuropharmacology and microbiome research, including the Datta lecture award from FEBS in 2022. In this interview, he outlines how he became interested in the role of the microbiome in brain development and disease, provides advice to budding scientists and highlights the broader public health implications of his research.
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The physiological consequences of a very large natural meal in a voracious marine fish, the staghorn sculpin (Leptocottus armatus).
Little information exists on physiological consequences when wild fish eat natural food. Staghorn sculpins at 10-13°C voluntarily consumed 15.8% of their body mass in anchovies. Gastric clearance was slow with >60% of the meal retained in the stomach at 48 h, and was not complete until 84 h. At 14-24 h post-feeding, pH was depressed by 3 units and Cl- concentration was elevated 2-fold in gastric chyme, reflecting HCl secretion, while in all sections of the intestine, pH declined by 1 pH unit but Cl- concentration remained unchanged. PCO2 and total ammonia concentration were greatly elevated throughout the tract, whereas PNH3 and HCO3- concentration were depressed. Intestinal HCO3- secretion rates, measured in gut sacs in vitro, were also lower in fed fish. Whole-animal O2 consumption rate was elevated approximately 2-fold for 72 h post-feeding, reflecting 'specific dynamic action', whereas ammonia and urea-N excretion rates were elevated about 5-fold. Arterial blood exhibited a modest 'alkaline tide' for about 48 h, but there was negligible excretion of metabolic base to the external seawater. PaCO2 and PaO2 remained unchanged. Plasma total amino acid concentration and total lipid concentration were elevated about 1.5-fold for at least 48 h, whereas small increases in plasma total ammonia concentration, PNH3 and urea-N concentration were quickly attenuated. Plasma glucose concentration remained unchanged. We conclude that despite the very large meal, slow processing with high efficiency minimizes internal physiological disturbances. This differs greatly from the picture provided by previous studies on aquacultured species using synthetic diets and/or force-feeding. Questions remain about the role of the gastro-intestinal microbiome in nitrogen and acid-base metabolism.