The Relationship between Gut Microbiome and Cognition in Older Australians

Ageing is associated with changes in biological processes, including reductions in cognitive functions and gut microbiome diversity. However, not much is known about the relationship between cognition and the microbiome with increasing age. Therefore, we examined the relationship between the gut microbiome and cognition in 69 healthy participants aged 60–75 years. The gut microbiome was analysed with the 16S rRNA sequencing method. The cognitive assessment included the Cognitive Drug Research computerised assessment battery, which produced five cognitive factors corresponding to ‘Quality of Episodic Secondary Memory’, ‘Quality of Working Memory’, ‘Continuity of Attention, ‘Speed of Memory’ and ‘Power of Concentration’. Multiple linear regression showed that the bacterial family Carnobacteriaceae explained 9% of the variance in predicting Quality of Episodic Secondary Memory. Alcaligenaceae and Clostridiaceae explained 15% of the variance in predicting Quality of Working Memory; Bacteroidaceae, Barnesiellaceae, Rikenellaceae and Gemellaceae explained 11% of the variance in Power of Concentration. The present study provides specific evidence of a relationship between specific families of bacteria and different domains of cognition.     

BMI,Alcohol Consumption and Gut Microbiome Species Richness Are Related to Structural and Functional Neurological Abnormalities

Background: The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA microbiome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10⁻⁷) and species richness (p = 1.2 × 10⁻⁸) in the case group as well as significant differences in beta diversity between cases and controls (Bray–Curtis: p = 9.99 × 10⁻⁴; Jaccard: p = 9.99 × 10⁻⁴). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10⁻³). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies.     

The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.     

The Microbiota–Gut–Brain Axis in Depression: The Potential Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect

Depression is a kind of worldwide mental illness with the highest morbidity and disability rate, which is often accompanied by gastrointestinal symptoms. Experiments have demonstrated that the disorder of the intestinal microbial system structure plays a crucial role in depression. The gut–brain axis manifests a potential linkage between the digestion system and the central nervous system (CNS). Nowadays, it has become an emerging trend to treat diseases by targeting intestinal microorganisms (e.g., probiotics) and combining the gut–brain axis mechanism. Combined with the research, we found that the incidence of depression is closely linked to the gut microbiota. Moreover, the transformation of the gut microbiota system structure is considered to have both positive and negative regulatory effects on the development of depression. This article reviewed the mechanism of bidirectional interaction in the gut–brain axis and existing symptom-relieving measures and antidepression treatments related to the gut microbiome.     

The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting,a Systematic Review—Gut Permeability as Potential Treatment Target

Muscle wasting is a frequently observed, inflammation-driven condition in aging and disease, known as sarcopenia and cachexia. Current treatment strategies target the muscle directly and are often not able to reverse the process. Because a reduced gut function is related to systemic inflammation, this might be an indirect target to ameliorate muscle wasting, by administering pro-, pre-, and synbiotics. Therefore, this review aimed to study the potential of pro-, pre-, and synbiotics to treat muscle wasting and to elucidate which metabolites and mechanisms affect the organ crosstalk in cachexia. Overall, the literature shows that Lactobacillus species pluralis (spp.) and possibly other genera, such as Bifidobacterium, can ameliorate muscle wasting in mouse models. The beneficial effects of Lactobacillus spp. supplementation may be attributed to its potential to improve microbiome balance and to its reported capacity to reduce gut permeability. A subsequent literature search revealed that the reduction of a high gut permeability coincided with improved muscle mass or strength, which shows an association between gut permeability and muscle mass. A possible working mechanism is proposed, involving lactate, butyrate, and reduced inflammation in gut–brain–muscle crosstalk. Thus, reducing gut permeability via Lactobacillus spp. supplementation could be a potential treatment strategy for muscle wasting.     

Medicinal Plants and Their Impact on the Gut Microbiome in Mental Health: A Systematic Review

Background: Various neurocognitive and mental health-related conditions have been associated with the gut microbiome, implicating a microbiome–gut–brain axis (MGBA). The aim of this systematic review was to identify, categorize, and review clinical evidence supporting medicinal plants for the treatment of mental disorders and studies on their interactions with the gut microbiota. Methods: This review included medicinal plants for which clinical studies on depression, sleeping disorders, anxiety, or cognitive dysfunction as well as scientific evidence of interaction with the gut microbiome were available. The studies were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eighty-five studies met the inclusion criteria and covered thirty mental health-related medicinal plants with data on interaction with the gut microbiome. Conclusion: Only a few studies have been specifically designed to assess how herbal preparations affect MGBA-related targets or pathways. However, many studies provide hints of a possible interaction with the MGBA, such as an increased abundance of health-beneficial microorganisms, anti-inflammatory effects, or MGBA-related pathway effects by gut microbial metabolites. Data for Panax ginseng, Schisandra chinensis, and Salvia rosmarinus indicate that the interaction of their constituents with the gut microbiota could mediate mental health benefits. Studies specifically assessing the effects on MGBA-related pathways are still required for most medicinal plants.     

From Gut Microbiota through Low-Grade Inflammation to Obesity: Key Players and Potential Targets

During the last decades, the gut microbiota has gained much interest in relation to human health. Mounting evidence has shown a strict association between gut microbiota and obesity and its related diseases. Inflammation has been appointed as the driving force behind this association. Therefore, a better understanding of the mechanisms by which gut microbiota might influence inflammation in the host could pave for the identification of effective strategies to reduce inflammation-related diseases, such as obesity and obesity-related diseases. For this purpose, we carried out an extensive literature search for studies published in the English language during the last 10 years. Most relevant studies were used to provide a comprehensive view of all aspects related to the association of gut microbiota and low-grade inflammation with obesity. Accordingly, this narrative review reports the evidence on the key players supporting the role of gut microbiota in the modulation of inflammation in relation to obesity and its complications. Moreover, therapeutic approaches to reduce microbiota-related inflammation are discussed to provide potential targets for future research.     

The Role of Gut Bacterial Metabolites in Brain Development,Aging and Disease

In the last decade, emerging evidence has reported correlations between the gut microbiome and human health and disease, including those affecting the brain. We performed a systematic assessment of the available literature focusing on gut bacterial metabolites and their associations with diseases of the central nervous system (CNS). The bacterial metabolites short-chain fatty acids (SCFAs) as well as non-SCFAs like amino acid metabolites (AAMs) and bacterial amyloids are described in particular. We found significantly altered SCFA levels in patients with autism spectrum disorder (ASD), affective disorders, multiple sclerosis (MS) and Parkinson’s disease (PD). Non-SCFAs yielded less significantly distinct changes in faecal levels of patients and healthy controls, with the majority of findings were derived from urinary and blood samples. Preclinical studies have implicated different bacterial metabolites with potentially beneficial as well as detrimental mechanisms in brain diseases. Examples include immunomodulation and changes in catecholamine production by histone deacetylase inhibition, anti-inflammatory effects through activity on the aryl hydrocarbon receptor and involvement in protein misfolding. Overall, our findings highlight the existence of altered bacterial metabolites in patients across various brain diseases, as well as potential neuroactive effects by which gut-derived SCFAs, p-cresol, indole derivatives and bacterial amyloids could impact disease development and progression. The findings summarized in this review could lead to further insights into the gut–brain–axis and thus into potential diagnostic, therapeutic or preventive strategies in brain diseases.     

Infant Gut Microbiota Associated with Fine Motor Skills

BACKGROUND: During early life, dynamic gut colonization and brain development co-occur with potential cross-talk mechanisms affecting behaviour. METHODS: We used 16S rRNA gene sequencing to examine the associations between gut microbiota and neurodevelopmental outcomes assessed by the Bayley Scales of Infant Development III in 71 full-term healthy infants at 18 months of age. We hypothesized that children would differ in gut microbial diversity, enterotypes obtained by Dirichlet multinomial mixture analysis and specific taxa based on their behavioural characteristics. RESULTS: In children dichotomized by behavioural trait performance in above- and below-median groups, weighted Unifrac b-diversity exhibited significant differences in fine motor (FM) activity. Dirichlet multinomial mixture modelling identified two enterotypes strongly associated with FM outcomes. When controlling for maternal pre-gestational BMI and breastfeeding for up to 3 months, the examination of signature taxa in FM groups showed that Turicibacter and Parabacteroides were highly abundant in the below-median FM group, while Collinsella, Coprococcus, Enterococcus, Fusobacterium, Holdemanella, Propionibacterium, Roseburia, Veillonella, an unassigned genus within Veillonellaceae and, interestingly, probiotic Bifidobacterium and Lactobacillus were more abundant in the above-median FM group. CONCLUSIONS: Our results suggest an association between enterotypes and specific genera with FM activity and may represent an opportunity for probiotic interventions relevant to treatment for motor disorders.     

Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity,Skin Health and Cellular Senescence

The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies.     

The Interaction of Polyphenols and the Gut Microbiota in Neurodegenerative Diseases

Polyphenols are secondary metabolites of plants and play a potential role in the prevention and treatment of neurodegenerative diseases (NND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to their unique physiological functions such as acting as antioxidants, being anti-inflammatory, being neuroprotective, and promoting intestinal health. Since dietary polyphenols exist in plant foods in the form of glycosylation or esterification or are combined with polymers, they need to undergo extensive metabolism through phase I and phase II biotransformations by various intestinal enzymes, as well as metabolism by the intestinal microbiota before they can be fully absorbed. Polyphenols improve intestinal microbiota disorders by influencing the structure and function of intestinal microbiota, inducing beneficial bacteria to produce a variety of metabolites such as short-chain fatty acids (SCFAs), promoting the secretion of hormones and neurotransmitters, and playing an important role in the prevention and treatment of NND by affecting the microbe–gut–brain axis. We review the ways in which some polyphenols can change the composition of the intestinal microbiota and their metabolites in AD or PD animal models to exert the role of slowing down the progression of NND, aiming to provide evidence for the role of polyphenols in slowing the progression of NND via the microbiota–gut–brain (MGB) axis.     

Impact of Dietary Arachidonic Acid on Gut Microbiota Composition and Gut–Brain Axis in Male BALB/C Mice

Although arachidonic acid (ARA) is the precursor of the majority of eicosanoids, its influence as a food component on health is not well known. Therefore, we investigated its impact on the gut microbiota and gut–brain axis. Groups of male BALB/c mice were fed either a standard diet containing 5% lipids (Std-ARA) or 15%-lipid diets without ARA (HL-ARA) or with 1% ARA (HL + ARA) for 9 weeks. Fatty acid profiles of all three diets were the same. The HL-ARA diet favored the growth of Bifidobacterium pseudolongum contrary to the HL + ARA diet that favored the pro-inflammatory Escherichia–Shigella genus in fecal microbiota. Dietary ARA intake induced 4- and 15-fold colic overexpression of the pro-inflammatory markers IL-1β and CD40, respectively, without affecting those of TNFα and adiponectin. In the brain, dietary ARA intake led to moderate overexpression of GFAP in the hippocampus and cortex. Both the hyperlipidic diets reduced IL-6 and IL-12 in the brain. For the first time, it was shown that dietary ARA altered the gut microbiota, led to low-grade colic inflammation, and induced astrogliosis in the brain. Further work is necessary to determine the involved mechanisms.     

In Vitro Gut Fermentation of Whey Protein Hydrolysate: An Evaluation of Its Potential Modulation on Infant Gut Microbiome

Whey protein and its hydrolysate are ubiquitously consumed as nutritional supplements. This study aimed to evaluate the potential effect of whey protein hydrolysate (WPH) on the infant gut microbiome, which is more variable than that of adults. Colonic fermentation was simulated through a static digestion model and fecal culture fermentation, using feces from normal infants aged from 1–3 years old. During in vitro gut fermentation, measurements of short-chain fatty acids (SCFA) concentrations and 16S rRNA amplicon sequencing were performed. Additionally, the growth curves of cultivated probiotics were analyzed to evaluate the prebiotic potential of WPH. Besides the decline of pH in fermentation, the addition of WPH induced a significant increase in the SCFA production and also the relative abundance of Proteobacteria, Bacteroides, and Streptococcus (p < 0.05). The lower ratio of Firmicutes/Bacteroidetes in WPH-supplemented samples indicated the positive modulation of WPH on the gut microbiota, which could benefit the energy balance and metabolism of infants. The stimulation effect of WPH on the probiotics (particularly Lactobacillus acidophilus NCFM) during cultivation implied the prebiotic potential as well. Our findings shed light on WPH as a valuable dietary supplement with not only enriched resources of essential amino acids but also the potential to restore the infant gut microbiome.     

A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.     

The Relationship between Gut Microbiota and Respiratory Tract Infections in Childhood: A Narrative Review

Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the “inter-talk” between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.     

Probiotic as a Potential Gut Microbiome Modifier for Stroke Treatment: A Systematic Scoping Review of In Vitro and In Vivo Studies

Background: Pharmacologic and non-pharmacologic treatments for stroke are essential but can be costly or harmful, whereas probiotics are a promising alternative. This scoping review aimed to synthesize the in vitro and in vivo evidence of probiotics on stroke-related neurological, biochemical, and histochemical outcomes. Methods: A systematic review was conducted in PubMed, Embase, and Cochrane Central Register of Clinical Trials (CENTRAL) up to 7 May 2021. Titles and abstracts were screened and assessed by two independent reviewers. The initial screening criteria aimed to include studies using probiotics, prebiotics, and symbiotics both in vitro and in vivo for the prevention and/or treatment of stroke. Results: Of 6293 articles, 4990 passed the initial screen after excluding duplication articles, of which 36 theme-related full texts were assessed and 13 were included in this review. No in vitro studies passed the criteria to be included in this review. Probiotics can ameliorate neurological deficits and show their anti-inflammation and anti-oxidative properties. Decreased loss of cerebral volume and inhibition of neuronal apoptosis were revealed in histopathological evidence. Conclusions: There are potential cognitive benefits of probiotic supplementation, especially among animal models, on decreasing cerebral volume, increasing neurological score, and decreasing the inflammatory response. However, further investigation is needed to validate these conclusions in various populations.     

The Role of Diet and Interventions on Multiple Sclerosis: A Review

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent clinical features include visual loss and sensorimotor symptoms and mainly affects those of young age. Some of the factors affecting its pathogenesis are genetic and/or environmental including viruses, smoking, obesity, and nutrition. Current research provides evidence that diet may influence MS onset, course, and quality of life of the patients. In this review, we address the role of nutrition on MS pathogenesis as well as dietary interventions that show promising beneficial results with respect to MS activity and progression. Investigation with large prospective clinical studies is required in order to thoroughly evaluate the role of diet in MS.     

Metabolic Responses to Butyrate Supplementation in LF- and HF-Fed Mice Are Cohort-Dependent and Associated with Changes in Composition and Function of the Gut Microbiota

The gut microbiota and associated metabolites have emerged as potential modulators of pathophysiological changes in obesity and related metabolic disorders. Butyrate, a product of bacterial fermentation, has been shown to have beneficial effects in obesity and rodent models of diet-induced obesity. Here, we aimed to determine the beneficial effects of butyrate (as glycerol ester of butyrate monobutyrin, MB) supplementation on metabolic phenotype, intestinal permeability and inflammation, feeding behavior, and the gut microbiota in low-fat (LF)- and high-fat (HF)-fed mice. Two cohorts (separated by 2 weeks) of male C57BL/6J mice (n = 24 in each cohort, 6/group/cohort; 6 weeks old) were separated into four weight-matched groups and fed either a LF (10 % fat/kcal) or HF (45% fat/kcal) with or without supplementation of MB (LF/MB or HF/MB) at 0.25% (w/v) in drinking water for 6 weeks. Metabolic phenotypes (body weight and adiposity), intestinal inflammation, feeding behavior, and fecal microbiome and metabolites were measured. Despite identical genetic and experimental conditions, we found marked differences between cohorts in the response (body weight gain, adiposity, and intestinal permeability) to HF-diet and MB. Notably, the composition of the gut microbiota was significantly different between cohorts, characterized by lower species richness and differential abundance of a large number of taxa, including subtaxa from five phyla, including increased abundance of the genera Bacteroides, Proteobacteria, and Parasutterella in cohort 2 compared to cohort 1. These differences may have contributed to the differential response in intestinal permeability to the HF diet in cohort 2. MB supplementation had no significant effect on metabolic phenotype, but there was a trend to protect from HF-induced impairments in intestinal barrier function in cohort 1 and in sensitivity to cholecystokinin (CCK) in both cohorts. These data support the concept that microbiota composition may have a crucial effect on metabolic responses of a host to dietary interventions and highlight the importance of taking steps to ensure reproducibility in rodent studies.     

Gut Reactions: How Far Are We from Understanding and Manipulating the Microbiota Complexity and the Interaction with Its Host? Lessons from Autism Spectrum Disorder Studies

Autism is a group of neurodevelopmental disorders, characterized by early onset difficulties in social communication and restricted, repetitive behaviors and interests. It is characterized by familial aggregation, suggesting that genetic factors play a role in disease development, in addition to developmentally early environmental factors. Here, we review the role of the gut microbiome in autism, as it has been characterized in case-control studies. We discuss how methodological differences may have led to inconclusive or contradictory results, even though a disproportion between harmful and beneficial bacteria is generally described in autism. Furthermore, we review the studies concerning the effects of gut microbial-based and dietary interventions on autism symptoms. Also, in this case, the results are not comparable due to the lack of standardized methods. Therefore, autism-specific microbiome signatures and, consequently, possible microbiome-oriented interventions are far from being recognized. We argue that a multi-omic longitudinal implementation may be useful to study metabolic changes connected to microbiome changes.     

Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation

Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research.