Diet constitutes a major source of nutrient flow to the gut microbes. As such, it can be used to help shape the gut microbiome. Fecal microbiota transplantation (FMT) is an increasingly promising therapy in disease states beyond recurrent Clostridioides difficile infection, but diet is largely overlooked for its potential to help optimize this therapy. Therefore, the aim of this scoping review is to present the literature landscape that captures pre- and post-FMT dietary intake in humans, identify research gaps, and provide recommendations for future research. A comprehensive search strategy was developed and searches were run in five databases. Studies were included if they discussed adults who underwent FMT for any recognized treatment indication and had dietary intake as a study objective, this search encompassed studies with interventions that included foods and dietary supplements. The initial screening identified a total of 7721 articles, of which 18 met the inclusion criteria for this review. Studies were heterogeneous, but taken together, they introduce a framework that defines important nutritional considerations for both donors and FMT recipients in the period around FMT dosing. This framework is summarized with this review and highlights the opportunities available to develop FMT-based precision nutrition strategies to optimize its clinical efficacy.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

Fresh vegetables harbor diverse microorganisms on leaf surfaces, yet their viral communities remain unexplored. We investigate the diversity and ecology of phyllosphere viromes of six leafy green vegetables using virus-like particle (VLP) enrichment and shotgun metagenome sequencing. On average, 9.2 × 107 viruses are present per gram of leaf tissue. The majority (93.1 ± 6.2%) of these viruses are taxonomically unclassified. Virome compositions are distinct among vegetable types and exhibit temporal variations. Virulent phages with replication-enhancing auxiliary metabolic genes (AMGs) are more dominant than temperate phages with host fitness-benefiting AMGs. Analysis of 1498 human fecal VLP metagenomes reveals that approximately 10% of vegetable viruses are present in the human gut virome, including viruses commonly observed in multiple studies. These gut-associated vegetable viruses are enriched with short-term vegetable intake, and depleted in individuals with metabolic and immunologic disorders. Overall, this study elucidates the ecological contribution of the fresh vegetable virome to human gut virome diversity.

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.

Dissemination of organisms from the gut microbiota is a major contributor to sepsis and critical illness. Patients with cirrhosis are prone to systemic infections and are commonly prescribed the carbohydrate lactulose to manage hepatic encephalopathy (HE) 1 . Commensal metabolism of lactulose is believed to reduce pathobiont colonization through short-chain fatty acid production, but its direct effects on gut pathobionts remain unexplored 2 . Here, we show that lactulose consumption unexpectedly selects for mutations in Escherichia coli lactose (lac) operon regulation, enhancing its metabolic fitness and colonization capacity. This is mediated by selection for constitutive expression of the lac operon through mutations in its regulatory components. Using in vitro systems, murine models, and clinical samples, we demonstrate that these mutations enable E. coli to exploit lactulose as a carbon source, bypassing host carbohydrate metabolism and increasing its intestinal colonization. Despite its long-standing use in HE treatment, we find that lactulose has a paradoxical association with risk of infection hospitalization in patients with cirrhosis in a large epidemiologic study. The emergence of lactulose-adapted E. coli strains could be suppressed by a dietary oligosaccharide that competitively inhibits lactulose uptake. These findings reveal a mechanism by which dietary substrates exert selective pressure on the microbiome, with implications for diet-based strategies to modulate microbial evolution and infection risk.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of morbidity worldwide. In Algeria, it ranks second in mortality-related deaths. Poor lifestyle, characterized by a low-fiber diet, insufficient physical activity, tobacco use, and alcohol consumption, is strongly associated with an increased risk of developing this disease. Probiotics have demonstrated anti-inflammatory and antitumor effects in preclinical and clinical studies. The World Health Organization (WHO) and European Food Safety Authority (EFSA) have recognized their safety and effectiveness, classifying them as Generally Recognized as Safe (GRAS) and Qualified Presumption of Safety (QPS), respectively. Probiotics exhibit immunomodulatory effects and maintain the equilibrium of the gut microbiota. However, the evidence for their clinical efficacy is inadequate, and additional research is requisite to establish them as therapeutic agents rather than simply as dietary supplements. Although probiotics are, in most cases, safe, high-risk patients should exercise caution due to the potential risk of infection. This review examines the current knowledge on probiotic strains, their therapeutic potential for colorectal cancer, limitations, and areas where further research is imperative to improve their efficacy.

The gut microbiome, a dynamic and integral component of human health, has co-evolved with its host, playing essential roles in metabolism, immunity, and disease prevention. Traditional microbiome studies, primarily focused on microbial composition, have provided limited insights into the functional and mechanistic interactions between microbiota and their host. The advent of multi-omics technologies has transformed microbiome research by integrating genomics, transcriptomics, proteomics, and metabolomics, offering a comprehensive, systems-level understanding of microbial ecology and host-microbiome interactions. These advances have propelled innovations in personalized medicine, enabling more precise diagnostics and targeted therapeutic strategies. This review highlights recent breakthroughs in microbiome research, demonstrating how these approaches have elucidated microbial functions and their implications for health and disease. Additionally, it underscores the necessity of standardizing multi-omics methodologies, conducting large-scale cohort studies, and developing novel platforms for mechanistic studies, which are critical steps toward translating microbiome research into clinical applications and advancing precision medicine.

Exposure to a diversity of microbes has been implicated in playing a major role in susceptibility to the development of allergic lung type diseases. The hygiene hypothesis suggests that those exposed to a broad diversity of microbes are more likely to be protected against developing allergic type diseases. However, changes in exposure to microbial diversity can occur in both younger individuals, as well as in adults, and the effects are not always understood.

We investigated the effect of exposure to broad microbial diversity on the airway T cell response in house dust mite (HDM) induced allergic airway disease (AAD, a model of allergic asthma).

We increased exposure to broad microbial diversity by co-housing specific pathogen free (SPF) adult or newborn mice with pet store mice (PSE or BiPSE, respectively). Mice were then exposed to HDM to induce AAD.

We found that the effect of increased microbial exposure on the development of allergic airway inflammation differs by age. Increasing exposure to diverse microbes as adults exacerbates the development of allergic airway inflammation, whereas this was not observed when exposure occurred at birth.

We suggest that experimental evaluation of the hygiene hypothesis in inflammation, particularly those using mouse models, may need to consider age of the host and time of microbial exposure.

Mouse models of increased exposure to diverse microbial environment shown to differentially affect the development of allergic airway inflammation, depending on the age of microbial exposure.

Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes (13C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with 13C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.

Prebiotic oligosaccharides are dietary supplements that modulate the intestinal gut microbiome by selectively nourishing subsets of the microbial community with a goal to enhance host health. To date, the diversity of polysaccharide compositions in the fiber consumed by humans is not well represented by the limited scope of oligosaccharide compositions present in current commercial prebiotics. Recently, our UC Davis group developed a novel method to generate oligosaccharides from any polysaccharide fiber, termed Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG). Using this method, sugar beet pulp (SBP) was transformed into sugar beet oligosaccharides (SBOs) composed of arabinose- and galactose-containing oligosaccharides. Fecal fermentations of SBO and SBP produced similar shifts in donor-specific bacterial communities and acid metabolite profiles with a general enrichment of Bacteroides and Bifidobacterium. However, in vitro tests revealed more Bifidobacterium strains could consume SBO than sugar beet arabinan, and specific strains showed differential consumption of arabinofuranooligosaccharides or galactooligosaccharide (GOS) portions of the SBO pool. Genomic and glycomic comparisons suggest that previously characterized, arabinan-specific, extracellular arabinofuranosidases from Bifidobacterium are not necessary to metabolize the arabino-oligosaccharides within SBO. Synbiotic application of SBO with an SBO-consuming strain Bifidobacterium longum subsp. longum SC596 in serial fecal enrichments resulted in enhanced persistence among 9 of 10 donor feces. This work demonstrates a novel workflow whereby FITDOG creates novel oligosaccharide pools that can provide insight into how compositional differences in fiber drive differential gut fermentation behaviors as well as their downstream health impacts. Moreover, these oligosaccharides may be useful in new prebiotic and synbiotic applications.IMPORTANCEPrebiotics seek to selectively alter the host microbiome composition or function, resulting in a concurrent health benefit to the host. However, commercial prebiotics represent a small fraction of the diversity of food polysaccharide compositions. In this work a novel method, Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG) was used to generate an oligosaccharide pool from sugar beet pulp (SBP). Sugar beet oligosaccharides (SBOs) resulted in similar changes to SBP in fecal enrichments; however, SBO could be consumed by more beneficial bifidobacterial strains than the cognate polysaccharide. These results demonstrate how the details of glycan structure have a profound influence on how gut bacteria metabolize food carbohydrates. The implications of this work are relevant to understanding how different dietary sources influence the human microbiome and extend to developing novel oligosaccharide pools for prebiotic applications.

The persistent organic pollutant of water by residual antibiotics, particularly tetracycline, posed serious environmental and health risks. Biochar dissolved organic matter (BDOM) sorbed pollutants and mitigated migration and transformation. This study investigates the binding interaction mechanisms between BDOM and tetracycline under varying pyrolysis temperatures biochars and pH, with fluorescence quenching techniques. The influence of biochar pyrolysis temperature on tetracycline adsorption behavior by BDOM-tetracycline was also researched. The key results revealed that higher pyrolysis temperatures and lower solution pH enhanced the binding affinity of BDOM for tetracycline, which was mainly attributed to increased aromaticity and reduced oxygen-containing functional groups. The hydrophobic forces of biochar dominated the interaction, with positive enthalpy (ΔH) and entropy (ΔS) values confirming an endothermic, entropy-driven process. The BDOM modified the mobility and bioavailability of tetracycline in the process of environmental pollution remediation, which not only enhances plant growth, but also mitigates ecological risks.

A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of L. reuteri strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The diet also beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable cardiometabolic benefits were observed independently of L. reuteri administration, several of which could be accurately predicted by baseline and diet-responsive microbiome features. The findings suggest that a dietary intervention targeted toward restoring the gut microbiome can improve host-microbiome interactions that likely underpin chronic pathologies, which can guide dietary recommendations and the development of therapeutic and nutritional strategies.

Laboratory mice (Mus musculus domesticus) harbor gut bacterial strains that are distinct from those of wild mice but whose evolutionary histories are unclear. Here, we show that laboratory mice have retained gut bacterial lineages that diversified in parallel (co-diversified) with rodent species for > 25 million years, but that laboratory-mouse gut microbiota (LGM) strains of these ancestral symbionts have experienced accelerated accumulation of genetic load during the past ~ 120 years of captivity. Compared to closely related wild-mouse gut microbiota (WGM) strains, co-diversified LGM strains displayed significantly faster genome-wide rates of nonsynonymous substitutions, indicating elevated genetic drift-a difference that was absent in non-co-diversified symbiont clades. Competition experiments in germ-free mice further indicated that LGM strains within co-diversified clades displayed significantly reduced fitness in vivo compared to WGM relatives to an extent not observed within non-co-diversified clades. Thus, stochastic processes (e.g., bottlenecks), not natural selection in the laboratory, have been the predominant evolutionary forces underlying divergence of co-diversified symbiont strains between laboratory and wild house mice. Our results show that gut bacterial lineages conserved in diverse rodent species have acquired novel mutational burdens in laboratory mice, providing an evolutionary rationale for restoring laboratory mice with wild gut bacterial strain diversity.

Long-term alterations of the gut microbiota and host symbiosis after a dietary perturbation remain insufficiently understood and characterized. In this study, we investigate the impact of temporary dietary fiber depletion in mice that received a diet with reduced fiber content (RFD) for 3 weeks followed by a return to a standard chow diet for 6 weeks, compared to mice that only received a chow diet. Fiber deprivation was accompanied by a reduction of microbiota diversity and an increase in mucolytic and sulfate-reducing bacteria. The activities of enzymes targeting glycans from the host mucus were increased accordingly, while those targeting plant fibers were decreased. On the host side, we report transiently higher quantities of host DNA in feces during the RFD suggesting an impaired gut barrier function. Six weeks after the return to the chow diet, lasting changes in microbiota composition were observed, as exemplified by the replacement of durably depleted amplicon sequence variants close to Duncaniella dubosii by other members of the Muribaculaceae family. The observation of two distinct gut microbial communities in mice under identical environmental and alimentary conditions at the end of the experiment suggests the existence of alternative stable microbiota states.

In this article, the authors explore the impact of a diet with reduced fiber content on the gut microbiota-host symbiosis in a mouse model. More importantly, they examine the resilience of the intestinal symbiosis after the return to a standard (chow) diet. Some of the measured parameters (intestinal barrier impairment and bacterial glycan-degrading enzymatic activities) returned to control values. However, this was not the case for bacterial richness-the number of different bacteria observed-which remained durably reduced. Among related bacteria, some groups receded and remained undetected until 6 weeks after the return to the chow diet while others saw their abundance increase in replacement. The authors find that a temporary fiber deprivation lasting as little as 3 weeks can cause a transition to an alternative stable microbiota state, i.e., a lasting change in intestinal microbiota composition.

The healthy gut microbiome is important in maintaining health and preventing various chronic and metabolic diseases through interactions with the host via different gut-organ axes, such as the gut-brain, gut-liver, gut-immune, and gut-lung axes. The human gut microbiome is relatively stable, yet can be influenced by numerous factors, such as diet, infections, chronic diseases, and medications which may disrupt its composition and function. Therefore, microbial resilience is suggested as one of the key characteristics of a healthy gut microbiome in humans. However, our understanding of its definition and indicators remains unclear due to insufficient experimental data. Here, we review the impact of key drivers including intrinsic and extrinsic factors such as diet and antibiotics on the human gut microbiome. Additionally, we discuss the concept of a resilient gut microbiome and highlight potential biomarkers including diversity indices and some bacterial taxa as recovery-associated bacteria, resistance genes, antimicrobial peptides, and functional flexibility. These biomarkers can facilitate the identification and prediction of healthy and resilient microbiomes, particularly in precision medicine, through diagnostic tools or machine learning approaches especially after antimicrobial medications that may cause stable dysbiosis. Furthermore, we review current nutrition intervention strategies to maximize microbial resilience, the challenges in investigating microbiome resilience, and future directions in this field of research.

Recent research underscores the crucial role of the gut microbiota in human health, particularly during states of altered homeostasis, including pregnancy. Additionally, it is not well understood how dietary changes during pregnancy affect the development of microbiomes of both mother and child.

Here, we describe the study design and methods for our randomized controlled trial, the fermented and fiber-rich foods on maternal and offspring microbiome study (FeFiFo-MOMS). We enrolled 135 women during early pregnancy, randomizing them to one of four diet arms: increased fiber, increased fermented foods, increase in both, and no dietary intervention as a comparator arm. Samples were collected across pregnancy continuing to 18 months post-birth for clinical, microbiome, and immune marker analysis.

Our trial design intended to investigate the effects of dietary interventions-specifically, increased intake of high-fiber and fermented foods-on maternal gut microbiota diversity and its subsequent transmission to infants.

The FeFiFo-MOMS trial was designed to provide valuable insights into the modifiable dietary factors that could influence maternal and infant health through microbiota-mediated mechanisms and examine the broader implications of diet on pregnant mothers' and infants' health and disease.

govID:NCT05123612.

The disruptive effect of antibiotics on the composition and function of the human microbiota is well established. However, the hypothesis that probiotics can help restore the antibiotic-disrupted microbiota has been advanced, with little consideration of the strength of evidence supporting it. Some clinical data suggest that probiotics can reduce antibiotic-related side effects, including Clostridioides difficile-associated diarrhoea, but there are no data that causally link these clinical effects to microbiota protection or recovery. Substantial challenges hinder attempts to address this hypothesis, including the absence of consensus on the composition of a 'normal' microbiota, non-standardized and evolving microbiome measurement methods, and substantial inter-individual microbiota variation. In this Review, we explore these complexities. First, we review the known benefits and risks of antibiotics, the effect of antibiotics on the human microbiota, the resilience and adaptability of the microbiota, and how microbiota restoration might be defined and measured. Subsequently, we explore the evidence for the efficacy of probiotics in preventing disruption or aiding microbiota recovery post-antibiotic treatment. Finally, we offer insights into the current state of research and suggest directions for future research.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell development, cytokine production, and intestinal barrier integrity. While balanced microbiota fosters immune tolerance, dysbiosis disrupts immune regulation, damages intestinal permeability, and heightens the risk of autoimmune diseases. The critical factor in shaping the gut microbiota and modulating immune response is diet. Research shows that high-fat diets rich in saturated fats are associated with disease progression. Conversely, diets rich in fruits, yogurt, and legumes may lower the risk of MS onset and progression. Specific dietary interventions, such as the Mediterranean diet (MD) and ketogenic diet, have shown potential to reduce inflammation, support neuroprotection, and promote CNS repair. Probiotics, by restoring microbial balance, may also help mitigate immune dysfunction noted in MS. Personalized dietary strategies targeting the gut microbiota hold promise for managing MS by modulating immune responses and slowing disease progression. Optimizing nutrient intake and adopting anti-inflammatory diets could improve disease control and quality of life. Understanding gut-immune interactions is essential for developing tailored nutritional therapies for MS patients.

Most brain development occurs in the "first 1000 days", a critical period from conception to a child's second birthday. Critical brain processes that occur during this time include synaptogenesis, myelination, neural pruning, and the formation of functioning neuronal circuits. Perturbations during the first 1000 days likely contribute to later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, including the maturation and colonization of the infant microbiome and its metabolites, specifically neurotransmitters, immune modulators, vitamins, and short-chain fatty acids. Successful microbiome maturation and gut-brain axis function depend on maternal factors (stress and exposure to toxins during pregnancy), mode of delivery, quality of the postnatal environment, diet after weaning from breast milk, and nutritional deficiencies. While the neonatal microbiome is highly plastic, it remains prone to dysbiosis which, once established, may persist into adulthood, thereby inducing the development of chronic inflammation and abnormal excitatory/inhibitory balance, resulting in neural excitation. Both are recognized as key pathophysiological processes in the development of ALS.

Altered gut microbiota has emerged as a major contributing factor to the etiology of chronic conditions in humans. Antibiotic exposure, historically dating back to the mass production of penicillin in the early 1940s, has been proposed as a primary contributor to the cumulative alteration of microbiota over generations. However, the mechanistic link between the antibiotics-altered microbiota and chronic conditions remains unclear.

In this study, we discovered that variants of the key beneficial gut microbe, Akkermansia muciniphila, were selected upon exposure to penicillin. These variants had mutations in the promoter of a TEM-type β-lactamase gene or pur genes encoding the de novo purine biosynthesis pathway, and they exhibited compromised abilities to mitigate host obesity in a murine model. Notably, variants of A. muciniphila are prevalent in the human microbiome worldwide.

These findings highlight a previously unknown mechanism through which antibiotics influence host health by affecting the beneficial capacities of the key gut microbes. Furthermore, the global prevalence of A. muciniphila variants raises the possibility that these variants contribute to global epidemics of chronic conditions, warranting further investigations in human populations. Video Abstract.

The gut microbiota (GM) plays an essential role in human health, influencing not only digestive processes but also the immune system´s functionality. The COVID-19 pandemic has highlighted the complex interaction between viral infections and the GM. Emerging evidence has demonstrated that SARS-CoV-2 can disrupt microbial homeostasis, leading to dysbiosis and compromised immune responses. The severity of COVID-19 has been associated with a reduction in the abundance of several beneficial bacteria in the gut. It has been proposed that consuming probiotics may help to re-colonize the GM. Although probiotics are important, prebiotics are essential for their metabolism, growth, and re-colonization capabilities. This chapter delves into the critical role of prebiotics in restoring GM after COVID-19 disease. The mechanisms by which prebiotics enhance the metabolism of beneficial bacteria will be described, and how prebiotics mediate the re-colonization of the gut with beneficial bacteria, thereby restoring microbial diversity and promoting the resilience of the gut-associated immune system. The benefits of consuming prebiotics from natural sources are superior to those from chemically purified commercial products.

Despite the importance of gut commensal microbiota to human health, there is little knowledge about their evolutionary histories, including their demographic histories and distributions of fitness effects (DFEs) of mutations. Here, we infer the demographic histories and DFEs for amino acid-changing mutations of 39 of the most prevalent and abundant commensal gut microbial species found in Westernized individuals over timescales exceeding human generations. Some species display contractions in population size and others expansions, with several of these events coinciding with several key historical moments in human history. DFEs across species vary from highly to mildly deleterious, with differences between accessory and core gene DFEs largely driven by genetic drift. Within genera, DFEs tend to be more congruent, reflective of underlying phylogenetic relationships. Together, these findings suggest that gut microbes have distinct demographic and selective histories.

Stroke represents the primary cause of death and persistent disability globally, leading to around 5.5 million annual patient fatalities. The objective was to explore the relationship of dietary fiber with all-cause and cardiovascular disease (CVD) mortality risk in patients with stroke.

We extracted stroke patients' data from the National Health and Nutrition Examination Survey (NHANES) database. All-cause and CVD mortality were outcomes. Dietary fiber consists of non-digestible forms of carbohydrates, usually polysaccharides that originate from plant-based foods. Covariates including demographic data, vital signs, comorbidities, laboratory parameters, and medication use were screened using the weighted multivariate Cox regression models with backward elimination. Weighted univariate and multivariate Cox regression models were performed to explore the relationship between dietary fiber intake and all-cause/CVD mortality, with hazard ratios (HRs) and 95% confidence intervals (CIs). The association was further investigated in different subgroups.

A total of 1,578 patients with stroke were included, of whom 688 (43.6%) died. Total fiber and vegetable fiber intake were analyzed as categorical variables, and the lowest intake was considered reference groups. High intake of total fiber (HR, 0.73; 95% CI, 0.57-0.94) and high intake of vegetable fiber (HR, 0.63; 95% CI, 0.48-0.82) were related to lower all-cause mortality risk in individuals with stroke. Similar findings were also observed between higher total fiber (HR, 0.56; 95% CI, 0.37-0.85) and vegetable fiber intake (HR, 0.57; 95% CI, 0.36-0.89) with decreased CVD mortality risk. The relationship between higher total fiber intake and lower all-cause mortality risk was discovered in individuals aged ≥ 60 yrs, smoking, non-CVD, and chronic kidney disease (CKD). High total fiber, or vegetable fiber consumption was linked to lower CVD mortality risk in stroke individuals aged ≥ 60 yrs, females, body mass index ≥ 30 kg/m2, non-smoking, and CKD.

Dietary fiber intake and vegetable fiber intake may benefit the prognosis of patients with stroke. Increasing dietary fiber consumption, especially vegetable fiber intake, potentially benefits the prognosis of stroke patients.

Nutrition, the gut microbiota and immunity are all important factors in the maintenance of health. However, there is a growing realization of the complex interplay between these elements coalescing in a nutrition-gut microbiota-immunity axis. This regulatory axis is critical for health with disruption being implicated in a broad range of diseases, including autoimmune disorders, allergies and mental health disorders. This new perspective continues to underpin a growing number of innovative therapeutic strategies targeting different elements of this axis to treat relevant diseases. This review describes the inter-relationships between nutrition, the gut microbiota and immunity. It then details several human diseases where disruption of the nutrition-gut microbiota-immunity axis has been identified and presents examples of how the various elements may be targeted therapeutically as alternate treatment strategies for these diseases.

Evolutionary perspectives have yielded profound insights in health and medical sciences. A fundamental recognition is that modern diet and lifestyle practices are mismatched with the human physiological constitution, shaped over eons in response to environmental selective pressures. This Darwinian angle can help illuminate and resolve issues in nutrition, including the contentious issue of fat consumption. In the present paper, the intake of saturated fat in ancestral and contemporary dietary settings is discussed. It is shown that while saturated fatty acids have been consumed by human ancestors across time and space, they do not feature dominantly in the diets of hunter-gatherers or projected nutritional inputs of genetic accommodation. A higher intake of high-fat dairy and meat products produces a divergent fatty acid profile that can increase the risk of cardiovascular and inflammatory disease and decrease the overall satiating-, antioxidant-, and nutrient capacity of the diet. By prioritizing fiber-rich and micronutrient-dense foods, as well as items with a higher proportion of unsaturated fatty acids, and in particular the long-chain polyunsaturated omega-3 fatty acids, a nutritional profile that is better aligned with that of wild and natural diets is achieved. This would help prevent the burdening diseases of civilization, including heart disease, cancer, and neurodegenerative conditions. Saturated fat is a natural part of a balanced diet; however, caution is warranted in a food environment that differs markedly from the one to which we are adapted.

Urolithin A (uroA) is a polyphenol derived from the multi-step metabolism of dietary ellagitannins by the human gut microbiota. Once absorbed, uroA can trigger mitophagy and aryl hydrocarbon receptor signaling pathways, altering host immune function, mitochondrial health, and intestinal barrier integrity. Most individuals harbor a microbiota capable of uroA production; however, the mechanisms underlying the dehydroxylation of its catechol-containing precursor (uroC) are unknown. Here, we use a combination of untargeted bacterial transcriptomics, proteomics, and comparative genomics to uncover an inducible uroC dehydroxylase (ucd) operon in Enterocloster species. We show that the ucd operon encodes a predicted molybdopterin-dependent enzyme complex that dehydroxylates urolithins at a specific position (9-OH). By interrogating publicly available metagenomics datasets, we observed that uroC-metabolizing Enterocloster species and ucd operon genes are prevalent in human feces. In ex vivo experiments with human fecal samples, only samples actively transcribing ucd could produce uroA, possibly explaining differences in urolithin metabolism between individuals. Collectively, this work identifies Enterocloster species and the ucd operon as important contributors to uroA production and establishes a multi-omics framework to further our mechanistic understanding of polyphenol metabolism by the human gut microbiota.

This review investigates the levels of antibiotic residues in animal products, types of antibiotics, and their possible impact on human health in Africa. The literature search involved the use of a systematic survey using data that were published from Africa from 2015 to 2024. The search terms used the Boolean operators with keywords such as antibiotics, antibiotic residues, antibiotics in animal products in Africa, and impact on human health. Only research conducted in Africa was used in the present study. The findings showed that the most prevalent groups of antibiotic residues were aminoglycoside, macrolides, β-lactams, fluoroquinolones, tetracyclines sulfonamides, and phenicols. Tetracycline showed the most prevalent antibiotic residue with 43% mostly from East Africa, followed by sulfonamides at 19%, and β-lactams at 16%; most of the antibiotic residue levels were higher than the World Health Organization permissible limit. Noncompliance with withdrawal periods and maximum residue limits for antibiotics used in food-producing animals may lead to negative outcomes such as allergic reactions, teratogenicity, carcinogenicity, microbiome alterations, and, most notably, antibiotic resistance. As a result, there is a need for constant monitoring of antibiotic residues in animal products in addition to the consideration of alternatives to antibiotics in order to avoid their health implications.

In the current era, malnutrition is seen as both undernutrition and overweight and obesity; both conditions are caused by nutrient deficiency or excess and improper use or imbalance in the intake of macro and micronutrients. Recent evidence suggests that malnutrition alters the intestinal microbiota, known as dysbiosis. Secretory immunoglobulin A (sIgA) plays an important role in maintaining and increasing beneficial intestinal microbiota populations and protecting against pathogenic species. Depletion of beneficial bacterial populations throughout life is also conditioned by malnutrition. This review aims to synthesize the evidence that establishes an interrelationship between diet, malnutrition, changes in the intestinal flora, and sIgA levels. Targeted nutritional therapies combined with prebiotic, probiotic, and postbiotic administration can restore the immune response in the intestine and the host's homeostasis.

Introduction: The shaping of the human intestinal microbiota starts during the intrauterine period and continues through the subsequent stages of extrauterine life. The microbiota plays a significant role in the predisposition and development of immune diseases, as well as various inflammatory processes. Importantly, the proper colonization of the fetal digestive system is influenced by maternal microbiota, the method of pregnancy completion and the further formation of the microbiota. In the subsequent stages of a child's life, breastfeeding, diet and the use of antibiotics influence the state of eubiosis, which determines proper growth and development from the neonatal period to adulthood. The literature data suggest that there is evidence to confirm that the intestinal microbiota of the infant plays an important role in regulating the immune response associated with the development of allergic diseases. However, the identification of specific bacterial species in relation to specific types of reactions in allergic diseases is the basic problem. Background: The main aim of the review was to demonstrate the influence of the microbiota of the mother, fetus and newborn on the functioning of the immune system in the context of allergies and asthma. Methods: We reviewed and thoroughly analyzed the content of over 1000 articles and abstracts between the beginning of June and the end of August 2024. Over 150 articles were selected for the detailed study. Results: The selection was based on the PubMed National Library of Medicine search engine, using selected keywords: "the impact of intestinal microbiota on the development of immune diseases and asthma", "intestinal microbiota and allergic diseases", "the impact of intrauterine microbiota on the development of asthma", "intrauterine microbiota and immune diseases", "intrauterine microbiota and atopic dermatitis", "intrauterine microbiota and food allergies", "maternal microbiota", "fetal microbiota" and "neonatal microbiota". The above relationships constituted the main criteria for including articles in the analysis. Conclusions: In the present review, we showed a relationship between the proper maternal microbiota and the normal functioning of the fetal and neonatal immune system. The state of eubiosis with an adequate amount and diversity of microbiota is essential in preventing the development of immune and allergic diseases. The way the microbiota is shaped, resulting from the health-promoting behavior of pregnant women, the rational conduct of the medical staff and the proper performance of the diagnostic and therapeutic process, is necessary to maintain the health of the mother and the child. Therefore, an appropriate lifestyle, rational antibiotic therapy as well as the way of completing the pregnancy are indispensable in the prevention of the above conditions. At the same time, considering the intestinal microbiota of the newborn in relation to the genera and phyla of bacteria that have a potentially protective effect, it is worth noting that the use of suitable probiotics and prebiotics seems to contribute to the protective effect.

Plant-derived exosome-like nanoparticles (PELNs) are natural nanocarriers and effective delivery systems for plant microRNAs (miRNAs). These PELN-carrying plant miRNAs can regulate mammalian genes across species, thereby increasing the diversity of miRNAs in mammals and exerting multi-target effects that play a crucial role in diseases, particularly cancer. PELNs demonstrate exceptional stability, biocompatibility, and targeting capabilities that protect and facilitate the up-take and cross-kingdom communication of plant miRNAs in mammals. Primarily ingested and absorbed within the gastrointestinal tract of mammals, PELNs preferentially act on the intestine to regulate intestinal homeostasis through functional miRNA activity. The oncogenesis and progression of cancer are closely associated with disruptions in intestinal barriers, ecological imbalances, as well as secondary changes, such as abnormal inflammatory reactions caused by them. Therefore, it is imperative to investigate whether PELNs exert their anticancer effects by regulating mammalian intestinal homeostasis and inflammation. This review aims to elucidate the intrinsic crosstalk relationships and mechanisms of PELNs-mediated miRNAs in maintaining intestinal homeostasis, regulating inflammation and cancer treatment. Furthermore, serving as exceptional drug delivery systems for miRNAs molecules, PELNs offer broad prospects for future applications, including new drug research and development along with drug carrier selection within targeted drug delivery approaches for cancer therapy.

Diet significantly influences the human gut microbiota, a key player in health. We analyzed shotgun metagenomic sequencing data from healthy individuals with long-term dietary patterns-vegan, flexitarian, or omnivore-and included detailed dietary surveys and blood biomarkers. Dietary patterns notably affected the bacterial community composition by altering the relative abundances of certain species but had a minimal impact on microbial functional repertoires. However, diet influenced microbial functionality at the strain level, with diet type linked to strain genetic variations. We also found molecular signatures of selective pressure in species enriched by specific diets. Notably, species enriched in omnivores exhibited stronger positive selection, such as multiple iron-regulating genes in the meat-favoring bacterium Odoribacter splanchnicus, an effect that was also validated in independent cohorts. Our findings offer insights into how diet shapes species and genetic diversity in the human gut microbiota.

The consumption of prey intestines and their content, known as gastrophagy, is well-documented among Arctic Indigenous peoples, particularly Inuit. In Greenland, Inuit consume intestines from various animals, including the ptarmigan, a small herbivorous grouse bird. While gastrophagy provides the potential to transfer a large number of intestinal microorganisms from prey to predator, including to the human gut, its microbial implications remain to be investigated. This study addresses this gap by investigating the microbial composition of the Greenlandic rock ptarmigan's gastrointestinal tract by analyzing the crop, stomach, and intestines while also comparing it with the microbiota found in garum, a fermented sauce made from ptarmigan meat and intestines. Through 16S rRNA gene sequencing, we assessed whether garum made from ptarmigan intestines provides access to microbial diversity otherwise only accessible through gastrophagy. Our findings reveal that garum made from ptarmigan intestines displayed distinct flavors and microbial composition similar to that found in the ptarmigan gut and intestines, highlighting the potential role of fermented products in mediating food microbial diversity associated with Indigenous food practices. Furthermore, our study underscores the broader importance of understanding microbial diversity in different food systems, particularly in the context of shifting dietary patterns and concerns about diminishing food microbial diversity. By elucidating the microbial richness gained through gastrophagy this research contributes to a deeper understanding of traditional and Indigenous foodways and their implications for human gut health.

Clinical studies strongly suggest the importance of diet quality on cognition in youth populations (15-24 years). The Mediterranean diet (MeDi) has been shown to improve cognition in contrast to the commonly consumed Western diet (WD). The gut microbiota may serve as a mechanism for diet-induced changes in cognition. Ten-week-old male Sprague Dawley rats were assigned a MeDi or WD (n=10/group) for 14 weeks. Prior to neurobehavior assessments, microbiota community composition was assessed. At the genus level, the relative abundance of four bacteria increased with the MeDi and five decreased compared to the WD. Rats in the MeDi group demonstrated cognitive flexibility and improvement in reference and working memory relative to the WD group. At the end of the study, serum cytokines were increased, and low-density lipoproteins were decreased in the MeDi group. Markers for neuroinflammation, blood-brain barrier, glial cells, and synaptic plasticity in brain regions did not differ between groups. Overall, the MeDi modulated gut microbiota, cognitive function, and serum lipid and cytokines but not gene expression in the brain compared to the WD. Further studies are needed to determine causality between diet-modulated gut microbiota, cognitive function, and immune function.

Understanding the relationship between dietary fat and physiological responses is crucial in species adapted to arid environments where water scarcity is common. In this study, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract and hypothalamus) and 17 phenotypic measurements, investigating the effects of dietary fat in the desert-adapted cactus mouse (Peromyscus eremicus). We show impacts on immune function, circadian gene regulation and mitochondrial function for mice fed a lower-fat diet compared with mice fed a higher-fat diet. In arid environments with severe water scarcity, even subtle changes in organismal health and water balance can affect physical performance, potentially impacting survival and reproductive success. This study sheds light on the complex interplay between diet, physiological processes and environmental adaptation, providing valuable insights into the multifaceted impacts of dietary choices on organismal well-being and adaptation strategies in arid habitats.

The macronutrient composition of a host's diet shapes its gut microbial community, with dietary fiber in particular escaping host digestion to serve as a potent carbon source for gut microbiota. Despite widespread recognition of fiber's importance to microbiome health, nutritional research often fails to differentiate hyper-processed fibers from cell-matrix-derived intrinsic fibers, limiting our understanding of how individual polysaccharides influence the gut community. We use the American cockroach (Periplaneta americana) as a model system to dissect the response of complex gut microbial communities to dietary modifications that are difficult to test in traditional host models. Here, we designed synthetic diets from lab-grade, purified ingredients to identify how the cockroach microbiome responds to six different carbohydrates (chitin, methylcellulose, microcrystalline cellulose, pectin, starch, and xylan) in otherwise balanced diets. We show via 16S rRNA gene profiling that these synthetic diets reduce bacterial diversity and alter the phylogenetic composition of cockroach gut microbiota in a fiber-dependent manner, regardless of the vitamin and protein content of the diet. Comparisons with cockroaches fed whole-food diets reveal that synthetic diets induce blooms in common cockroach-associated taxa and subsequently fragment previously stable microbial correlation networks. Our research leverages an unconventional microbiome model system and customizable lab-grade artificial diets to shed light on how purified polysaccharides, as opposed to nutritionally complex intrinsic fibers, exert substantial influence over a normally stable gut community.

Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.

The impact of dietary fiber on intestinal T cell development is poorly understood. Here we show that a low fiber diet reduces MHC-II antigen presentation by small intestinal epithelial cells (IECs) and consequently impairs development of CD4+CD8αα+ intraepithelial lymphocytes (DP IELs) through changes to the microbiota. Dietary fiber supports colonization by Segmented Filamentous Bacteria (SFB), which induces the secretion of IFNγ by type 1 innate lymphoid cells (ILC1s) that lead to MHC-II upregulation on IECs. IEC MHC-II expression caused either by SFB colonization or exogenous IFNγ administration induced differentiation of DP IELs. Finally, we show that a low fiber diet promotes overgrowth of Bifidobacterium pseudolongum, and that oral administration of B. pseudolongum reduces SFB abundance in the small intestine. Collectively we highlight the importance of dietary fiber in maintaining the balance among microbiota members that allow IEC MHC-II antigen presentation and define a mechanism of microbiota-ILC-IEC interactions participating in the development of intestinal intraepithelial T cells.

The latest Yakult Science Study Day was held virtually on 2 November 2023. Aimed at healthcare professionals, researchers, and students, a variety of experts explored the latest gut microbiome research and what it means in practice. The morning sessions discussed the role of the microbiome in health and disease, the rapid advancements in DNA sequencing and implications for personalised nutrition, the current state of evidence on health benefits associated with fermented foods, prebiotics and probiotics and the challenges involved in interpreting research in this area. The afternoon session considered the emerging research on the microbiota-gut-brain axis in mediating effects of food on mood, the bidirectional impact of menopause on the gut microbiota, and the interplay between the gut and skin with implications for the treatment of rare and common skin disorders. The session ended with an update on the use of faecal microbiota transplant in both research and clinical practice. Undoubtedly, the gut microbiome is emerging as a key conductor of human health, both in relation to gastrointestinal and non-gastrointestinal outcomes. As research continues to elucidate mechanisms of action and confirm their effects in human trials, the gut microbiome should be a key consideration within a holistic approach to health moving forward.