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Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review.
The composition and functioning of the gut microbiota, the complex population of microorganisms residing in the intestine, is strongly affected by endogenous and exogenous factors, among which diet is key. Important perturbations of the microbiota have been observed to contribute to disease risk, as in the case of neurological disorders, inflammatory bowel disease, obesity, diabetes, cardiovascular disease, among others. Although mechanisms are not fully clarified, nutrients interacting with the microbiota are thought to affect host metabolism, immune response or disrupt the protective functions of the intestinal barrier. Similarly, key intermediaries, whose presence may be strongly influenced by dietary habits, sustain the communication along the gut-brain-axis, influencing brain functions in the same way as the brain influences gut activity. Due to the role of diet in the modulation of the microbiota, its composition is of high interest in inherited errors of metabolism (IEMs) and may reveal an appealing therapeutic target. In IEMs, for example in phenylketonuria (PKU), since part of the therapeutic intervention is based on chronic or life-long tailored dietetic regimens, important variations of the microbial diversity or relative abundance have been observed. A holistic approach, including a healthy composition of the microbiota, is recommended to modulate host metabolism and affected neurological functions.
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Diet, gut microbiota, and the gut-brain axis: mechanistic interactions and therapeutic implications in neuropsychiatric disorders.
The gut microbiota is a dynamic trans-kingdom ecosystem that contributes to host immunological, metabolic, and neuroendocrine homeostasis through the microbiota-gut-brain axis (MGBA). Diet is one of the major environmental factors shaping this axis, as it influences microbial composition, microbial production of neuroactive metabolites, and intestinal barrier integrity. Dysbiosis has been increasingly associated with neurological, psychiatric, and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Experimental studies have identified several potential mechanisms linking gut microbiota to brain function, including immune modulation, vagus nerve signaling, microbial metabolite production, and blood-brain barrier regulation. However, translating these findings into clinical practice remains challenging because human studies are affected by genetic heterogeneity, dietary variation, medication use, lifestyle factors, and disease-specific confounders. In this review, we summarize current evidence on the interactions among diet, gut microbiota, and brain function, with particular emphasis on microbial metabolites, immune mediators, and barrier-related mechanisms. We also critically discuss microbiota-targeted interventions, including precision nutrition, probiotics, and fecal microbiota transplantation, highlighting both their therapeutic potential and their current limitations. A more cautious and mechanistically integrated understanding of the MGBA may support the development of personalized strategies for neuropsychiatric disease prevention and management.
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Exploring the potential relationships among obstructive sleep apnea, erectile dysfunction, and gut microbiota: a narrative review.
INTRODUCTION: Poor sleep quality is closely associated with comorbidities affecting a multitude of organ systems. Among the sleep disorders in the population, there has recently been an increase in the prevalence of obstructive sleep apnea (OSA), which has particularly affected men. The intermittent hypoxia and sleep fragmentation associated with OSA can result in the manifestation or aggravation of a number of pathophysiologic conditions, including the impairment of reproductive function in men and women. In this context, erectile dysfunction (ED) is of particular concern. Other consequences of OSA are changes in the gastrointestinal microbiota, with the resultant dysbiosis having potentially harmful consequences that promote downstream exacerbation of various comorbidities. OBJECTIVES: This narrative review aims to explore the potential relationships among ED, gut microbiota, and OSA. METHODS: A search of the relevant literature was performed in the PubMed, Embase, Medline, and Web of Science databases. RESULTS: Sleep is important for regulating the body's functions, and sleep deprivation can negatively affect health. OSA can damage organic functions, including reproductive function, and can lead to ED. Restoring the microbiota and improving sleep can help to improve sexual function or reverse ED and enhance other associated conditions mediated through the gut-brain axis relationship. Probiotics and prebiotics can be used as supportive strategies in the prevention and treatment of OSA, as they help to reduce systemic inflammation and improve intestinal barrier function. CONCLUSION: A good diet, a healthy lifestyle, and proper bowel function are essential in controlling depression and several other pathologies. Modulating the gut microbiota through probiotics and prebiotics can provide a viable strategy for developing new therapeutic options in treating many conditions. A better understanding of these a priori unrelated phenomena would foster our understanding of the effects of OSA on human fertility and how changes in gut microbiota may play a role.
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Adolescence and Aging: Impact of Adolescence Inflammatory Stress and Microbiota Alterations on Brain Development, Aging, and Neurodegeneration.
Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodeling is a heightened level of vulnerability to stressors and immune challenges. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, and use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging, such as Alzheimer's disease, Parkinson's disease, and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis, and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain, and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that the consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood.
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Sulforaphane alleviates DSS-induced colitis and gut-brain axis dysfunction potentially via microbiota-metabolism-HIF-1α crosstalk.
Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract, often accompanied by anxiety- and depression-like symptoms, which are closely associated with gut microbiota dysbiosis, metabolic disturbances, immune activation, and dysfunction of the gut-brain axis. Sulforaphane (SFN), a natural isothiocyanate, has been demonstrated in our previous studies to alleviate colitis in mice; however, its effects on UC-associated neurobehavioral abnormalities remain unclear. In this study, a dextran sulfate sodium (DSS)-induced colitis model was employed to investigate the effects of SFN on colitis and associated behavioral abnormalities. SFN significantly alleviated colitis symptoms and improved anxiety- and depression-like behaviors, accompanied by enhanced hippocampal structure and function. Mechanistically, SFN improved intestinal barrier integrity by increasing goblet cell abundance, upregulating MUC2 expression, and normalizing the expression of tight junction proteins, including Occludin, Claudin-1, Claudin-5, and ZO-1. SFN attenuated both peripheral and central inflammation responses and promoted anti-inflammatory macrophage polarization. In addition, SFN partially restored gut microbiota composition, increased short-chain fatty acid production, and improved amino acid and energy metabolism. DSS-induced colitis was associated with increased HIF-1α expression and glycolytic activation, whereas SFN inhibited HIF-1α signaling and downregulated the expression of glycolysis-related genes (Glut1, Pfkl, Ldha). GEO database analysis revealed that HIF-1α expression was significantly elevated in patients with active UC compared with both health controls and patients with inactive UC. Collectively, SFN ameliorates colitis and associated behavioral abnormalities, potentially through modulation of gut microbiota composition, metabolic reprogramming, and HIF-1α-related immunometabolic pathways.
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Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review.
The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.
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Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression.
The human gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Without this inherent microbial community, we would be unable to digest plant polysaccharides and would have trouble extracting lipids from our diet. Resident gut bacteria are an important contributor to healthy metabolism and there is significant evidence linking gut microbiota and metabolic disorders such as obesity and diabetes. In the past few years, neuroscience research has demonstrated the importance of microbiota in the development of brain systems that are vital to both stress reactivity and stress-related behaviours. Here we review recent literature that examines the impact of diet-induced changes in the microbiota on stress-related behaviours including anxiety and depression.
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The Effects of Walnuts and Academic Stress on Mental Health, General Well-Being and the Gut Microbiota in a Sample of University Students: A Randomised Clinical Trial.
Poorer mental health is common in undergraduate students due to academic stress. An interplay between stress and diet exists, with stress influencing food choices. Nutritional interventions may be effective in preventing mental health decline due to complex bidirectional interactions between the brain, the gut and the gut microbiota. Previous studies have shown walnut consumption has a positive effect on mental health. Here, using a randomized clinical trial (Australian New Zealand Clinical Trials Registry, #ACTRN12619000972123), we aimed to investigate the effects of academic stress and daily walnut consumption in university students on mental health, biochemical markers of general health, and the gut microbiota. We found academic stress had a negative impact on self-reported mood and mental health status, while daily walnut consumption improved mental health indicators and protected against some of the negative effects of academic stress on metabolic and stress biomarkers. Academic stress was associated with lower gut microbial diversity in females, which was improved by walnut consumption. The effects of academic stress or walnut consumption in male participants could not be established due to small numbers of participants. Thus, walnut consumption may have a protective effect against some of the negative impacts of academic stress, however sex-dependent mechanisms require further study.
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N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.
BACKGROUND: Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored. METHODS AND RESULTS: Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress. CONCLUSIONS: In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.
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Human Gut Microbiota in Health and Selected Cancers.
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto's thyroidis and Graves' disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.