The sialylation of intestinal mucins plays a crucial role in maintaining intestinal homeostasis and shaping the gut microbiota. This study aims to develop a mucin-like polymer to modulate the intestinal microbiota in the elderly individuals. We synthesized functionalized conjugates using sialic acid monomer, 3'-sialyllactose, and Gellan gum, resulting in a series of GG-sialoglycan conjugates with diverse glycan chain lengths and terminal structures. The sialic acid contents of GG-EDA-Sia, GG-EDA-SL, GG-HAD-Sia, and GG-HAD-SL were 28.48 %, 29.78 %, 23.45 and 41.58 %, respectively. These conjugates exhibited anti-digestion effects. In addition, they demonstrated favorable biocompatibility and exhibited notable anti-inflammatory properties. In vitro fermentation experiments using fecal bacteria from elderly individuals revealed that GG-sialoglycan conjugates enhanced the proliferation of beneficial bacteria such as Lactobacillus, Bifidobacterium, and Blautia, while simultaneously suppressing pathogens like Escherichia-Shigella. It is worth noting that GG-sialoglycan conjugates containing 3'-sialyllactose exhibited superior prebiotic activity compared to those with sialic acid monomer. In summary, our findings strongly support the promising potential of functional sialic acid-based macromolecular glycan conjugates as a novel strategy to improve aging-related intestinal health.

Background/Objectives: Recent studies have highlighted the role of the gut-muscle axis, suggesting that modulation of the gut microbiota may indirectly benefit skeletal muscle. This study aimed to evaluate the effects of Lactobacillus fermentum (L. fermentum) supplementation in a model of muscle atrophy induced by chronic ethanol (EtOH) intake, focusing on inflammatory and antioxidant mechanisms. Methods: Sixty 12-month-old female Balb/c mice were divided randomly into three groups (n = 20/group): (1) Ethanol (EtOH) group, receiving ethanol daily for 8 and 12 weeks to induce systemic oxidative stress and inflammation; (2) Ethanol + Probiotic (EtOH + P) group, receiving both ethanol and L. fermentum supplementation for the same durations; and (3) Control (Ctrl) group, receiving only water. Muscle samples were analyzed for the fiber morphology, inflammatory markers, oxidative stress indicators, and satellite cell (SC) activity. All data were tested for normality using the Shapiro-Wilk test before applying a parametric analysis. A statistical analysis was performed using one-way ANOVA followed by a Bonferroni post-hoc test. The level of significance was set at p < 0.05. Results: EtOH exposure caused significant atrophy in all muscle fiber types (type I, IIa, and IIb), with the most pronounced effects on oxidative fibers. L. fermentum supplementation significantly reversed atrophy in type I and IIa fibers, accompanied by a significant reduction in IL-6, TNF-α, and Hsp60 expression levels, indicating the protective effect of L. fermentum against oxidative stress and inflammation. Moreover, the probiotic treatment increased MyoD expression in SCs, suggesting enhanced regenerative activity, without histological evidence of fibrosis. Conclusions: These findings suggest that L. fermentum supplementation could counteract EtOH-induced skeletal muscle damage by reducing inflammation and oxidative stress and promoting muscle repair, indicating its potential as an adjuvant, in the therapeutic strategy of models of muscle degeneration.

Migraine is a common neurological disorder with potential pharmacological triggers. Proton pump inhibitors (PPIs), commonly prescribed for managing gastroesophageal reflux disease and other acid-related gastrointestinal disorders, have been linked to headaches. However, their association with migraine remains unclear. This systematic review and meta-analysis assessed the association between PPI use and the incidence of migraine.

A systematic search of PubMed, Embase, and Web of Science was conducted in accordance with the PRISMA framework and registered with PROSPERO (ID: CRD42025644604) to enhance transparency. The search, conducted up to January 2024, included studies focusing on the association between migraine and PPI use. Data screening and extraction were performed using Nested Knowledge software. Meta-analyses were conducted in R software, with heterogeneity assessed through the I² statistic. Pooled adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity analyses were also performed to assess the robustness of the results. Gender and migraine subtype were considered in subgroup analyses. Additionally, the GRADE approach was applied to assess the certainty of the evidence across the pooled outcomes.

Five studies involving over 1.5 million participants met the inclusion criteria. The overall pooled adjusted odds ratio (aOR) was 2.508 (95% CI, 0.790-7.969; I² = 91.2%). However, there was a significant association in males (aOR, 3.875; 95% CI, 2.413-6.222; I² = 0%) but not in females (aOR, 2.475; 95% CI, 0.563-10.890; I² = 91.1%). No significant differences were found between migraine types: with aura (aOR, 2.079; 95% CI, 0.945-4.576; I² = 25.4%) and without aura (aOR, 2.524; 95% CI, 0.807-7.896; I² = 96.5%). The GRADE assessment indicated a very low certainty of the evidence.

This review found no significant overall association between PPI use and migraine. However, a significant association was observed in males but not in females. Further research is needed to clarify this association and explore the underlying causality mechanisms, and migraine subtypes, particularly why the association appears more pronounced in males.

Not applicable.

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.

Inflammation mechanisms play a critical role in muscle homeostasis, and in Muscular Dystrophies (MDs), the myofiber damage triggers chronic inflammation which significantly controls the disease progression. Immunomodulatory strategies able to target inflammatory pathways and mitigate the immune-mediated damage in MDs may provide new therapeutic options. Owing to its capacity of influencing the immune response and enhancing tissue repair, stem cells' secretome has been proposed as an adjunct or standalone treatment for MDs. In this review study, we discuss the challenging points related to the inflammation condition characterizing MD pathology and provide a concise summary of the literature supporting the potential of perinatal stem cells in targeting and modulating the MD inflammation.

The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota's possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in β-diversity between those exposed to antidepressants and those not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations in antidepressant users include an increase in the Bacteroidetes phylum, Christensenellaceae family, and Bacteroides and Clostridium genera, while a decrease was found in the Firmicutes phylum, Ruminococcaceae family, and Ruminococcus genus. In addition, antidepressants attenuate gut microbial differences between depressed and healthy individuals, modulate microbial serotonin transport, and influence microbiota's metabolic functions. These include lyxose degradation, peptidoglycan maturation, membrane transport, and methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity and abundance of the Roseburia and Faecalibacterium genera, in the Firmicutes phylum, are associated with antidepressant response, emerging as promising biomarkers. This review highlights the potential for gut microbiota as a predictor of treatment response and emphasizes the need for further research to elucidate the mechanisms underlying antidepressant-microbiota interactions. More homogeneous studies and standardized techniques are required to confirm these initial findings.

During acute or chronic uremia, the cumulative harmful effects of uremic toxins result in numerous health problems and, ultimately, mortality. Previous research has identified that uremic retention solutes originate from the gut microbiome, indicating that uremia may be closely associated with gut microbiome dysbiosis. To deepen our understanding of the compositional characteristics of the gut microbiome in patients with uremia and thereby promote precision medicine in the treatment of uremia, we conducted a study of the compositional characteristics of the gut microbiome in 20 patients with uremia. The gut microbiome diversity of uremic patients and the control group showed certain differences. Nonmetric multidimensional scaling analysis showed that the beta diversity of the gut microbiome of uremic patients was significantly different from that of the healthy control individuals, with a distinct clustering effect in the uremic patient group, and it also showed a similarly distinct clustering effect in the healthy control group. The Chao1 index and Sobs index were significantly lower in the uremic patient group than in the healthy control group ( P < 0.05). By analyzing the composition and abundance distribution of the gut microbiome in the uremic patient group and healthy control group, we found that the relative abundance of the gut microbiome constituents Fusobacteriota , Enterobacteriaceae, Oscillospirales, Ruminococcaceae, and Lachnospiraceae was significantly increased in the intestines of uremic patients. We also detected the rare taxa Erysipelotrichaceae, which was present only in the uremic patient group. Predictive functional analysis suggested that an increased abundance of Ruminococcaceae and Lachnospirales, which are associated with indoxyl sulfate and phenylacetyl glutamine, and an increased abundance of Oscillospirales, which is associated with pyruvate metabolism, in uremic patients may strongly influence the gut environment according to renal function, resulting in dysbiosis associated with uremic toxin production. Rare taxa such as Erysipelotrichaceae have been suggested to be detrimental to intestinal disease. Further research into these gut microbiomes may provide new ideas for the prevention and treatment of uremia with the gut microbiome.

Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes, including falls, disability, incapacity and death. While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophysiology of frailty, direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.

To gain insight into gut dysbiosis in frail older adults.

Seven electronic databases (China National Knowledge Infrastructure, VIP, SinoMed, Wanfang, PubMed, Web of Science and EMBASE) were searched for articles published before October 31, 2023 to identify observational studies that compared the microbiomes of older adults with and without frailty. The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults. The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.

Eleven observational studies with 912 older adults were included in this review. Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults, with a significant decrease in α diversity and a significant increase in β diversity in frail older adults. The pooled results revealed that at the phylum level, four microbiota (Actinobacteria, Proteobacteria, Verrucomicrobia and Synergistetes) were significantly enriched, and two microbiota (Firmicutes and Fusobacteria) were significantly depleted in frail older adults. At the family level, the results consistently revealed that the abundances of 6 families, most of which belong to the Actinobacteria or Proteobacteria phylum, were greater in frail than in non-frail older adults. At the genus or species level, consistent results from more than two studies revealed that the abundances of the genera Prevotella, Faecalibacterium, and Roseburia were significantly lower in frail older adults; individual studies revealed that the abundances of some genera or species (e.g., Megamonas, Blautia, and Megasphaera) were significantly lower, whereas those of other genera or species (e.g., Bifidobacterium, Oscillospira, Ruminococcus and Pyramidobacter) were significantly greater in frail older adults.

This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults, which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species. However, further studies are needed to confirm these findings.

Agricultural activities are a significant contributor to global greenhouse gas emissions, accounting for 14.5% of total anthropogenic emissions. Specifically, greenhouse gas emissions from beef cattle and dairy cattle constitute 35% and 30% of total global livestock emissions, respectively. This study focuses on dairy cattle, exploring the complex relationships between rumen microbiota and methane emission. The methane emissions of 968 lactating Holstein cows were measured using a laser methane detector (LMD, Shanghai Hesai Technology Co., Ltd., Shanghai, China). Among the measured cows, 107 individuals were further selected into high (HME) and low methane-emitting (LME) groups, including 50 cows in the HME group and 57 in the LME group. This study analyzed differences in rumen microbiota and microbial functions between cows with varying levels of methane emissions. The results showed significant differences in the Simpson and Pielou indices of rumen bacterial communities between the HME and LME groups. Beta diversity analysis revealed significant differences in microbial community structure between the two groups. It was found that the abundance of Bacteroidales and Prevotellaceae in the rumen of cows in the HME group cows was significantly higher than that of cows in the LME group (LDA > 3, p < 0.05). Additionally, bacterial functions related to biosynthesis and carbohydrate metabolism were more active in the HME group. This study revealed distinct differences in the rumen bacterial communities between HME and LME cow in Chinese Holstein cattle, and identified specific bacteria and their functional differences in the HME group. The microbial characteristics and metabolic pathways provide new insights for developing strategies to reduce methane emissions, supporting the sustainable development of the dairy industry.

This paper explores the intricate relationship between depression, gut dysbiosis, and Clostridioides difficile infections, collectively termed "The 3 Ds". Depression is a widespread mental disorder increasing in prevalence. It is recognized for its societal burden and complex pathophysiology, encompassing genetic, environmental, and microbiome-related factors. The consequent increased use of antidepressants has led to growing concerns about their effects on the gut microbiome. Various classes of antidepressants and antipsychotics show antimicrobial activity, potentially leading to shifts in the gut microbiome and contributing to the development of dysbiosis. Dysbiosis, in turn, can predispose individuals to opportunistic infections like C. difficile, a significant healthcare concern due to its high recurrence rates and severe impact on patients' quality of life. Further, the link between antidepressant use and an increased risk of C. difficile infection (CDI) is explored and, finally, the emergence of live biotherapeutic products as novel treatment options for recurrent CDI is discussed.

The early-life gut microbiota (GM) is increasingly recognized for its contributions to human health and disease over time. Microbiota composition, influenced by factors like race, geography, lifestyle, and individual differences, is subject to change. The GM serves dual roles, defending against pathogens and shaping the host immune system. Disruptions in microbial composition can lead to immune dysregulation, impacting defense mechanisms. Additionally, GM aids digestion, releasing nutrients and influencing physiological systems like the liver, brain, and endocrine system through microbial metabolites. Dysbiosis disrupts intestinal homeostasis, contributing to age-related diseases. Recent studies are elucidating the bacterial species that characterize a healthy microbiota, defining what constitutes a 'healthy' colonic microbiota. The present review article focuses on the importance of microbiome composition for the development of homeostasis and the roles of GM during aging and the age-related diseases caused by the alteration in gut microbial communities. This article might also help the readers to find treatments targeting GM for the prevention of various diseases linked to it effectively.

In humans, gut microbiome (GM) differences are often correlated with, and sometimes causally implicated in, ageing. However, it is unclear how these findings translate in wild animal populations. Studies that investigate how GM dynamics change within individuals, and with declines in physiological condition, are needed to fully understand links between chronological age, senescence and the GM, but have rarely been done. Here, we use longitudinal data collected from a closed population of Seychelles warblers (Acrocephalus sechellensis) to investigate how bacterial GM alpha diversity, composition and stability are associated with host senescence. We hypothesised that GM diversity and composition will differ, and become more variable, in older adults, particularly in the terminal year prior to death, as the GM becomes increasingly dysregulated due to senescence. However, GM alpha diversity and composition remained largely invariable with respect to adult age and did not differ in an individual's terminal year. Furthermore, there was no evidence that the GM became more heterogenous in senescent age groups (individuals older than 6 years), or in the terminal year. Instead, environmental variables such as season, territory quality and time of day, were the strongest predictors of GM variation in adult Seychelles warblers. These results contrast with studies on humans, captive animal populations and some (but not all) studies on non-human primates, suggesting that GM deterioration may not be a universal hallmark of senescence in wild animal species. Further work is needed to disentangle the factors driving variation in GM-senescence relationships across different host taxa.

The prevalence of Clostridioides difficile infection in older and frail population is extremely high and adverse outcomes, including future recurrences and premature mortality, are common. Nonetheless, the clinical risk profile for Clostridioides difficile recurrence in older people is still controversial. We aimed to investigate: 1) the association between Clostridioides difficile recurrence and 6-month mortality; 2) the risk factors for Clostridioides difficile recurrence after hospital discharge.

This is a retrospective study on adults with a first episode of Clostridioides difficile infection admitted to all Internal Medicine and Geriatrics Units of the University Hospital of Ferrara (Italy) between January 2018 and December 2020. For each patient, sociodemographic, clinical and laboratory data were collected through hospital database system. The primary and secondary outcomes were mortality and recurrence within 6 months from the first infectious episode, respectively.

The mean age of the 386 enrolled patients was 77.8 years; 61.7% were females. Twelve percent patients had Clostridioides difficile recurrence and 32.1% patients died during the 6-month follow-up. At Cox analysis, after adjustment for the potential confounders, participants with recurrence reported a twofold risk of death compared to those without recurrence (HR, 95% CI 2.45, 1.59-3.78). Compared to patients treated with metronidazole, those treated with vancomycin showed a lower risk of recurrence (log-rank p < 0.001).

Clostridioides difficile recurrence is associated with a higher risk of mortality and it may itself be a marker of frailty and vulnerability. Vancomycin treatment during the infectious episode was associated with lower recurrence rate, as compared to metronidazole.

Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.

Chronic diseases (CD) may result from a combination of genetic factors, lifestyle and social behaviours, healthcare system influences, community factors, and environmental determinants of health. These risk factors frequently coexist and interact with one another. Ongoing research and a focus on personalized interventions are pivotal strategies for preventing and managing chronic disease outcomes. A wealth of literature suggests the potential involvement of gut microbiota in influencing host metabolism, thereby impacting various risk factors associated with chronic diseases. Dysbiosis, the perturbation of the composition and activity of the gut microbiota, is crucial in the etiopathogenesis of multiple CD. Recent studies indicate that specific microorganism-derived metabolites, including trimethylamine N-oxide, lipopolysaccharide and uremic toxins, contribute to subclinical inflammatory processes implicated in CD. Various factors, including diet, lifestyle, and medications, can alter the taxonomic species or abundance of gut microbiota. Researchers are currently dedicating efforts to understanding how the natural progression of microbiome development in humans affects health outcomes. Simultaneously, there is a focus on enhancing the understanding of microbiome-host molecular interactions. These endeavours ultimately aim to devise practical approaches for rehabilitating dysregulated human microbial ecosystems, intending to restore health and prevent diseases. This review investigates how the gut microbiome contributes to CD and explains ways to modulate it for managing or preventing chronic conditions.

The human gut microbiota is a dynamic community of microorganisms that undergo variable changes over the entire life span. To thoroughly investigate the possible fluctuations of the microbiota throughout human life, we performed a pooled analysis of healthy fecal samples across different age groups covering the entire human life span. Our study integrated data from 79 publicly available studies and new stool samples from an Italian cohort, i.e., the Parma Microbiota project, resulting in 6,653 samples processed through the shotgun metagenomic approach. This approach has allowed species-level taxonomic reconstruction of the gut microbiota and investigation of its metabolic potential across the human life span. From a taxonomic point of view, our findings confirmed and detailed at species-level accuracy that the microbial richness of the gut microbiota gradually increases in the first stage of life, becoming relatively stable during adolescence. Moreover, the analysis identified the potential core microbiota representative of distinct age groups, revealing age-related bacterial patterns and the continuous rearrangement of the microbiota in terms of relative abundances across the life span rather than the acquisition and loss of taxa. Furthermore, the shotgun approach provided insights into the functional contribution of the human gut microbiome. The metagenomic analysis revealed functional age-related differences, particularly in carbohydrate and fiber metabolism, suggesting a co-evolution of the microbiome assembly with diet. Additionally, we identified correlations between vitamin synthesis, such as thiamine and niacin, and early life, suggesting a potential role of the microbiome in human physiology, in particular in the functions of the host's nervous and immune systems.

In this study, we provided comprehensive insights into the dynamic nature of the human gut microbiota across the human life span. In detail, we analyzed a large data set based on a shotgun metagenomic approach, combining public data sets and new samples from the Parma Microbiota project and obtaining a detailed overview of the possible relationship between gut microbiota development and aging. Our findings confirmed the main stages in microbial richness development and revealed specific core microbiota associated with different age stages. Moreover, the shotgun metagenomic approach allowed the disentangling of the functional changes in the microbiome across the human life span, particularly in diet-related metabolism, which is probably correlated to bacterial co-evolution with dietary habits. Notably, our study also uncovered positive correlations with vitamin synthesis in early life, suggesting a possible impact of the microbiota on human physiology.

The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system.

Although olanzapine (OLZ) remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability issues related to its metabolic profile such as weight gain and dyslipidemia. Our previous studies have demonstrated that progesterone receptor membrane component 1 (PGRMC1) plays a key role in antipsychotic-induced metabolic side effects. Prebiotics showed positive effects on lipid metabolism, however, limited studies focused on their therapeutic potential and mechanisms in treating antipsychotic-induced lipid metabolic disorders. Herein, our study aims to explore the effects of the prebiotic B-GOS on lipid disturbances induced by OLZ and elucidate its underlying mechanisms via PGRMC1 pathway. In an 8-week study, long-term intraperitoneal administration of OLZ at a dosage of 8 mg/kg/day in mice induced lipid disturbances as manifested by significantly increased lipid indexes in plasma and liver. B-GOS effectively alleviated the OLZ-induced abnormal lipid metabolism by enhancing the diversity of the gut microbiota, with a 100-fold increase in Akkermansia abundance and a 10-fold decrease in Faecalibaculum abundance. Followed by the B-GOS related changes of gut microbiota, OLZ-induced substantial hepatic inhibition of PGRMC1, and associated protein factors of Wnt signaling pathway (Wnt3a, β-catenin, and PPAR-γ) were reversed without affecting plasma levels of short-chain fatty acids. Taken together, prebiotics like B-GOS enriching Akkermansia offer a promising novel approach to alleviate antipsychotic-induced lipid disturbances by modulating the PGRMC1-Wnt signaling pathway.

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

The gut microbiome is emerging as an important factor in signaling along the gut-brain axis. The intimate physiological connection between the gut and the brain allows perturbations in the microbiome to be directly transmitted to the central nervous system and thereby contribute to psychiatric and neurological diseases. Common microbiome perturbations result from the ingestion of xenobiotic compounds including pharmaceuticals such as psychotropic drugs. In recent years, a variety of interactions between these drug classes and the gut microbiome have been reported, ranging from direct inhibitory effects on gut bacteria to microbiome-mediated drug degradation or sequestration. Consequently, the microbiome may play a critical role in influencing the intensity, duration, and onset of therapeutic effects, as well as in influencing the side effects that patients may experience. Furthermore, because the composition of the microbiome varies from person to person, the microbiome may contribute to the frequently observed interpersonal differences in the response to these drugs. In this review, we first summarize the known interactions between xenobiotics and the gut microbiome. Then, for psychopharmaceuticals, we address the question of whether these interactions with gut bacteria are irrelevant for the host (i.e., merely confounding factors in metagenomic analyses) or whether they may even have therapeutic or adverse effects.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Mounting evidence underscores the intricate interplay between the immune system and skeletal muscles in Duchenne muscular dystrophy (DMD), as well as during regular muscle regeneration. While immune cell infiltration into skeletal muscles stands out as a prominent feature in the disease pathophysiology, a myriad of secondary defects involving metabolic and inflammatory pathways persist, with the key players yet to be fully elucidated. Steroids, currently the sole effective therapy for delaying onset and symptom control, come with adverse side effects, limiting their widespread use. Preliminary evidence spotlighting the distinctive features of T cell profiling in DMD prompts the immuno-characterization of circulating cells. A molecular analysis of their transcriptome and secretome holds the promise of identifying a subpopulation of cells suitable as disease biomarkers. Furthermore, it provides a gateway to unraveling new pathological pathways and pinpointing potential therapeutic targets. Simultaneously, the last decade has witnessed the emergence of novel approaches. The development and equilibrium of both innate and adaptive immune systems are intricately linked to the gut microbiota. Modulating microbiota-derived metabolites could potentially exacerbate muscle damage through immune system activation. Concurrently, genome sequencing has conferred clinical utility for rare disease diagnosis since innovative methodologies have been deployed to interpret the functional consequences of genomic variations. Despite numerous genes falling short as clinical targets for MD, the exploration of Tdark genes holds promise for unearthing novel and uncharted therapeutic insights. In the quest to expedite the translation of fundamental knowledge into clinical applications, the identification of novel biomarkers and disease targets is paramount. This initiative not only advances our understanding but also paves the way for the design of innovative therapeutic strategies, contributing to enhanced care for individuals grappling with these incapacitating diseases.

Antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed for depression treatment. Animal studies have shown that antidepressants can influence gut microbiota composition and specific bacterial taxa. We aimed to investigate the association between antidepressant use and human gut microbiota composition and functional pathway.

We collected information on antidepressant use, demographic, food patterns, and clinical characteristics through questionnaires and medical records. The gut microbiota profiles of 271 depressive patients were carried out through 16S rRNA gene sequencing. Patients were categorized based on different types of antidepressant use groups for gut microbiota comparisons. MaAsLin2 was performed to evaluate microbiota composition across groups. PICRUSt2 was used to predict microbiota functional pathways.

Patients taking SSRIs or SNRIs had a lower microbiota diversity. We found seven taxa abundances (Turicibacter, Barnesiella, Lachnospiraceae_ND3007_group, Romboutia, Akkermansia, Dialister, Romboutia and Fusicatenibacter) differed in patients with various types of antidepressants compared with those without antidepressant treatments (p < 0.05). Turicibacter inversely correlated with depression severity in SSRIs or SNRI users (r = -0.43, p < 0.05). Top identified pathways were related to compound fermentation and biosynthesis in microbiota function.

Antidepressant usage, especially SSRIs and SNRIs, associates with changes in gut microbiota composition and specific taxa. Given our study's preliminary cross-sectional nature, further research is warranted to comprehend the relationship between antidepressant use, treatment response, and gut microbiota, aiming to enhance therapeutic interventions in the future.

The global aging situation is severe, and the medical pressures associated with aging issues should not be underestimated. The need and feasibility of studying aging and intervening in aging have been confirmed. Aging is a complex natural physiological progression, which involves the irreversible deterioration of body cells, tissues, and organs with age, leading to enhanced risk of disease and ultimately death. The intestinal microbiota has a significant role in sustaining host dynamic balance, and the study of bidirectional communication networks such as the brain-gut axis provides important directions for human disease research. Moreover, the intestinal microbiota is intimately linked to aging. This review describes the intestinal microbiota changes in human aging and analyzes the causal controversy between gut microbiota changes and aging, which are believed to be mutually causal, mutually reinforcing, and inextricably linked. Finally, from an anti-aging perspective, this study summarizes how to achieve delayed aging by targeting the intestinal microbiota. Accordingly, the study aims to provide guidance for further research on the intestinal microbiota and aging.

The term "intestinal dysbiosis" is used for indicating change(s) of the intestinal microbiota which have been associated with the development of diseases and the deterioration of disease treatments in humans. In this review, documented clinical effects of drug-induced intestinal dysbiosis are briefly presented, and methodologies which could be considered for the management of drug-induced intestinal dysbiosis based on clinical data are critically reviewed. Until relevant methodologies are optimized and/or their effectiveness to the general population is confirmed, and, since drug-induced intestinal dysbiosis refers predominantly to antibiotic-specific intestinal dysbiosis, a pharmacokinetically-based approach for mitigating the impact of antimicrobial therapy on intestinal dysbiosis is proposed.

Elderly-onset inflammatory bowel disease [IBD] patients exhibit a distinct natural history compared to younger IBD patients, with unique disease phenotypes, differential responses to therapy, and increased surgical morbidity and mortality. Despite the foreseeable high demand for personalized medicine and specialized IBD care in the elderly, current paradigms of IBD management fail to capture the required nuances of care for elderly-onset IBD patients. Our review postulates the roles of systemic and mucosal immunosenescence, inflammageing and a dysbiotic microbial ecosystem in the pathophysiology of elderly-onset IBD. Ultimately, a better understanding of elderly-onset IBD can lead to improved patient outcomes and the tailoring of future preventative and treatment strategies.

Our aim was to investigate the association between gut microbiota and delirium occurrence in acutely ill older adults. We included 133 participants 65+ years consecutively admitted to the emergency department of a tertiary university hospital, between September 2019 and March 2020. We excluded candidates with ≥24-hour antibiotic utilization on admission, recent prebiotic or probiotic utilization, artificial nutrition, acute gastrointestinal disorders, severe traumatic brain injury, recent hospitalization, institutionalization, expected discharge ≤48 hours, or admission for end-of-life care. A trained research team followed a standardized interview protocol to collect sociodemographic, clinical, and laboratory data on admission and throughout the hospital stay. Our exposure measures were gut microbiota alpha and beta diversities, taxa relative abundance, and core microbiome. Our primary outcome was delirium, assessed twice daily using the Confusion Assessment Method. Delirium was detected in 38 participants (29%). We analyzed 257 swab samples. After adjusting for potential confounders, we observed that a greater alpha diversity (higher abundance and richness of microorganisms) was associated with a lower risk of delirium, as measured by the Shannon (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.60-0.99; p = .042) and Pielou indexes (OR = 0.69; 95% CI = 0.51-0.87; p = .005). Bacterial taxa associated with pro-inflammatory pathways (Enterobacteriaceae) and modulation of relevant neurotransmitters (Serratia: dopamine; Bacteroides, Parabacteroides: GABA) were more common in participants with delirium. Gut microbiota diversity and composition were significantly different in acutely ill hospitalized older adults who experienced delirium. Our work is an original proof-of-concept investigation that lays a foundation for future biomarker studies and potential therapeutic targets for delirium prevention and treatment.

A progressive degradation of the brain's structure and function, which results in a reduction in cognitive and motor skills, characterizes neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The morbidity linked to NDs is growing, which poses a severe threat to human being's mental and physical ability to live well. The gut-brain axis (GBA) is now known to have a crucial role in the emergence of NDs. The gut microbiota is a conduit for the GBA, a two-way communication system between the gut and the brain. The myriad microorganisms that make up the gut microbiota can affect brain physiology by transmitting numerous microbial chemicals from the gut to the brain via the GBA or neurological system. The synthesis of neurotransmitters, the immunological response, and the metabolism of lipids and glucose have all been demonstrated to be impacted by alterations in the gut microbiota, such as an imbalance of helpful and harmful bacteria. In order to develop innovative interventions and clinical therapies for NDs, it is crucial to comprehend the participation of the gut microbiota in these conditions. In addition to using antibiotics and other drugs to target particular bacterial species that may be a factor in NDs, this also includes using probiotics and other fecal microbiota transplantation to maintain a healthy gut microbiota. In conclusion, the examination of the GBA can aid in understanding the etiology and development of NDs, which may benefit the improvement of clinical treatments for these disorders and ND interventions. This review indicates existing knowledge about the involvement of microbiota present in the gut in NDs and potential treatment options.

Delirium is a clinical syndrome characterized by an acute change in attention, awareness and cognition with fluctuating course, frequently observed in older patients during hospitalization for acute medical illness or after surgery. Its pathogenesis is multifactorial and still not completely understood, but there is general consensus on the fact that it results from the interaction between an underlying predisposition, such as neurodegenerative diseases, and an acute stressor acting as a trigger, such as infection or anesthesia. Alterations in brain insulin sensitivity and metabolic function, increased blood-brain barrier permeability, neurotransmitter imbalances, abnormal microglial activation and neuroinflammation have all been involved in the pathophysiology of delirium. Interestingly, all these mechanisms can be regulated by the gut microbiota, as demonstrated in experimental studies investigating the microbiota-gut-brain axis in dementia. Aging is also associated with profound changes in gut microbiota composition and functions, which can influence several aspects of disease pathophysiology in the host. This review provides an overview of the emerging evidence linking age-related gut microbiota dysbiosis with delirium, opening new perspectives for the microbiota as a possible target of interventions aimed at delirium prevention and treatment.

Alzheimer's disease (AD) is a neurodegenerative disorder that causes gradual memory loss. AD and its prodromal stage of mild cognitive impairment (MCI) are marked by significant gut microbiome perturbations, also known as gut dysbiosis. However, the direction and extent of gut dysbiosis have not been elucidated. Therefore, we performed a meta-analysis and systematic review of 16S gut microbiome studies to gain insights into gut dysbiosis in AD and MCI.

We searched MEDLINE, Scopus, EMBASE, EBSCO, and Cochrane for AD gut microbiome studies published between Jan 1, 2010 and Mar 31, 2022. This study has two outcomes: primary and secondary. The primary outcomes explored the changes in α-diversity and relative abundance of microbial taxa, which were analyzed using a variance-weighted random-effects model. The secondary outcomes focused on qualitatively summarized β-diversity ordination and linear discriminant analysis effect sizes. The risk of bias was assessed using a methodology appropriate for the included case-control studies. The geographic cohorts' heterogeneity was examined using subgroup meta-analyses if sufficient studies reported the outcome. The study protocol has been registered with PROSPERO (CRD42022328141).

Seventeen studies with 679 AD and MCI patients and 632 controls were identified and analyzed. The cohort is 61.9% female with a mean age of 71.3±6.9 years. The meta-analysis shows an overall decrease in species richness in the AD gut microbiome. However, the phylum Bacteroides is consistently higher in US cohorts (standardised mean difference [SMD] 0.75, 95% confidence interval [CI] 0.37 to 1.13, p < 0.01) and lower in Chinese cohorts (SMD -0.79, 95% CI -1.32 to -0.25, p < 0.01). Moreover, the Phascolarctobacterium genus is shown to increase significantly, but only during the MCI stage.

Notwithstanding possible confounding from polypharmacy, our findings show the relevance of diet and lifestyle in AD pathophysiology. Our study presents evidence for region-specific changes in abundance of Bacteroides, a major constituent of the microbiome. Moreover, the increase in Phascolarctobacterium and the decrease in Bacteroides in MCI subjects shows that gut microbiome dysbiosis is initiated in the prodromal stage. Therefore, studies of the gut microbiome can facilitate early diagnosis and intervention in Alzheimer's disease and perhaps other neurodegenerative disorders.

Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with significant psychosocial and medical disease burden. Much difficulty has been encountered in developing novel therapeutics and objective biomarkers for clinical use in this population. In that regard, gut-microbial homeostasis appears to modulate several key pathways relevant to a variety of psychiatric, metabolic, and inflammatory disorders. Microbial impact on immune, endocrine, endocannabinoid, kynurenine, and other pathways are discussed throughout this review. Emphasis is placed on this system's relevance to current pharmacology, diet, and comorbid illness in bipolar disorder. Despite the high level of optimism promoted in many reviews on this topic, substantial obstacles exist before any microbiome-related findings can provide meaningful clinical utility. Beyond a comprehensive overview of pathophysiology, this review hopes to highlight several key areas where progress is needed. As well, novel microbiome-associated suggestions are presented for future research.

Sarcopenia, the age-related loss of muscle mass and function increasing the risk of disability and adverse outcomes in older people, is substantially influenced by dietary habits. Several studies from animal models of aging and muscle wasting indicate that the intake of specific polyphenol compounds can be associated with myoprotective effects, and improvements in muscle strength and performance. Such findings have also been confirmed in a smaller number of human studies. However, in the gut lumen, dietary polyphenols undergo extensive biotransformation by gut microbiota into a wide range of bioactive compounds, which substantially contribute to bioactivity on skeletal muscle. Thus, the beneficial effects of polyphenols may consistently vary across individuals, depending on the composition and metabolic functionality of gut bacterial communities. The understanding of such variability has recently been improved. For example, resveratrol and urolithin interaction with the microbiota can produce different biological effects according to the microbiota metabotype. In older individuals, the gut microbiota is frequently characterized by dysbiosis, overrepresentation of opportunistic pathogens, and increased inter-individual variability, which may contribute to increasing the variability of biological actions of phenolic compounds at the skeletal muscle level. These interactions should be taken into great consideration for designing effective nutritional strategies to counteract sarcopenia.

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that the gut and brain are in constant bidirectional communication, of which gut microbiota and its metabolic production are a major component, and form the so-called gut microbiome-brain axis. Disturbances of microbiota homeostasis caused by imbalance in their functional composition and metabolic activities, known as dysbiosis, cause dysregulation of these pathways and trigger changes in the blood-brain barrier permeability, thereby causing pathological malfunctions, including neurological and functional gastrointestinal disorders. In turn, the brain can affect the structure and function of gut microbiota through the autonomic nervous system by regulating gut motility, intestinal transit and secretion, and gut permeability. Here, we examine data from the CAS Content Collection, the largest collection of published scientific information, and analyze the publication landscape of recent research. We review the advances in knowledge related to the human gut microbiome, its complexity and functionality, its communication with the central nervous system, and the effect of the gut microbiome-brain axis on mental and gut health. We discuss correlations between gut microbiota composition and various diseases, specifically gastrointestinal and mental disorders. We also explore gut microbiota metabolites with regard to their impact on the brain and gut function and associated diseases. Finally, we assess clinical applications of gut-microbiota-related substances and metabolites with their development pipelines. We hope this review can serve as a useful resource in understanding the current knowledge on this emerging field in an effort to further solving of the remaining challenges and fulfilling its potential.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.