The gut microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in maintaining the delicate balance of human health. Emerging evidence suggests that microbiome disruptions can have far-reaching implications, ranging from the development of inflammatory diseases and cancer to metabolic disorders. Bacteriophages, or "phages", are viruses that specifically infect bacterial cells, and their interactions with the gut microbiome are receiving increased attention. Despite the recently revived interest in the gut phageome, it is still considered the "dark matter" of the gut, with more than 80% of viral genomes remaining uncharacterized. Today, research is focused on understanding the mechanisms by which phages influence the gut microbiota and their potential applications. Bacteriophages may regulate the relative abundance of bacterial communities, affect bacterial functions in various ways, and modulate mammalian host immunity. This review explores how phages can regulate bacterial functionality, particularly in gut commensals and pathogens, emphasizing their role in gut health and disease.

Asthma is a chronic disease affecting millions of children worldwide, and in severe cases requires hospitalization. The etiology of asthma is multifactorial, caused by both genetic and environmental factors. In recent years, the role of the early-life gut microbiome in relation to asthma has become apparent, supported by an increasing number of population studies, in vivo research, and intervention trials. Numerous early-life factors, which for decades have been associated with the risk of developing childhood asthma, are now being linked to the disease through alterations of the gut microbiome. These factors include cesarean birth, antibiotic use, breastfeeding, and having siblings or pets, among others. Association studies have highlighted several specific microbes that are altered in children developing asthma, but these can vary between studies and disease phenotype. This demonstrates the importance of the gut microbial ecosystem in asthma, and the necessity of well-designed studies to validate the underlying mechanisms and guide future clinical applications. In this review, we examine the current literature on the role of the gut microbiome in childhood asthma and identify research gaps to allow for future microbial-focused therapeutic applications in asthma.

Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.

Maternal probiotic supplementation altered the microbial composition in infants' gut, yet its effect on the functional pathways of the microbiota remains unclear. This study aimed to explore the potential impact of maternal probiotic intake on the predicted functional pathways of the gut microbiome in healthy infants. A total of 24 pregnant women were randomly allocated to either the control group or the probiotic group. The women in the probiotic group began receiving probiotics at the 32nd week of pregnancy and continued until delivery. Meconium and fecal samples were collected from infants at birth, as well as on the 3rd day, 14th day, and 6th month after birth. The functional characteristics of the microbial community were inferred using 16S rRNA gene analysis, processed with PICRUSt software, and cross-referenced with the KEGG database. The probiotic group had lower levels of Actinobacteria and Bacteroidetes, while Bifidobacterium growth was notably increased in the infant gut microbiota. At day 0 postpartum, the control group exhibited higher levels of Prevotellaceae compared to the probiotic group (P < 0.05). However, no significant differences were found by day 3. At day 14, the control group exhibited higher levels of Bacteroidaceae and Bacteroides, while Bacteroides_thetaiotaomicron was more abundant in the probiotic group (P < 0.05). By 6 months, the control group showed a higher abundance of Firmicutes (P < 0.05). On day 0 postpartum, maternal probiotic consumption increased the Environmental information processing pathway at KEGG Level 1, and increased Energy metabolism, Metabolism of cofactors and vitamins, and Cell growth and death pathways at KEGG Level 2. It also increased Histidine metabolism, One carbon pool by folate, and Folate biosynthesis at KEGG Level 3. No changes were observed in the infant gut microbiota's functional metabolic pathways at 3 days postpartum. At 14 days postpartum, probiotics reduced Lipid metabolism pathways at KEGG Level 2 and the Citrate cycle at KEGG Level 3. At 6 months postpartum, probiotics decreased Carbohydrate metabolism pathways at KEGG Level 2. Our findings suggest that probiotic supplementation during pregnancy affects the functional metabolism of the gut microbiota in healthy infants. This, in turn, may influence the development of the infant's immune system, metabolism, and overall health by modifying the gut microbial environment.

Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.

Vitamin B12, cobalamin, is indispensable for humans owing to its participation in two biochemical reactions: the conversion of l-methylmalonyl coenzyme A to succinyl coenzyme A, and the formation of methionine by methylation of homocysteine. Eukaryotes, encompassing plants, fungi, animals and humans, do not synthesise vitamin B12, in contrast to prokaryotes. Humans must consume it in their diet. The most important sources include meat, milk and dairy products, fish, shellfish and eggs. Due to this, vegetarians are at risk to develop a vitamin B12 deficiency and it is recommended that they consume fortified food. Vitamin B12 behaves differently to most vitamins of the B complex in several aspects, e.g. it is more stable, has a very specific mechanism of absorption and is stored in large amounts in the organism. This review summarises all its biological aspects (including its structure and natural sources as well as its stability in food, pharmacokinetics and physiological function) as well as causes, symptoms, diagnosis (with a summary of analytical methods for its measurement), prevention and treatment of its deficiency, and its pharmacological use and potential toxicity.

Foods prepared using microbial conversion of major and minor food components, which are otherwise known as fermented foods continue to impact human health. The live microorganisms and transformed metabolites can also have a deep influence on the gut microbiota, the multifaceted population of microorganisms dwelling inside the gut play a key role in wellbeing of an individual. The probiotic strains delivered through the consumption of fermented food and other bioactive components such as polyphenolic metabolites, bioactive peptides, short-chain fatty acids and others including those produced via gut microbiota mediated transformations have been proposed to balance the gut microbiota diversity and activity, and also to regulate the inflammation in the gut. However, little is known about such effects and only a handful of fermented foods have been explored to date. We herein review the recent knowledge on the dysbiotic gut microbiota linking to major gut inflammatory diseases. Also, evidences that fermented food consumption modulates the gut microbiota, and its impact on the gut inflammation and inflammatory diseases have been discussed. © 2024 Society of Chemical Industry.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Childhood obesity is a considerable public health issue. Recent research has shown that alterations in gut microbiota can have an impact on developing obesity and other metabolic health problems in children. This study aimed to investigate whether the characteristics of gut microbiota in obese children and adolescents are associated with the severity of obesity and any metabolic complications.

During May 2022 to May 2023, a total of 56 children and adolescents with obesity, aged 6-18 years, were recruited at Thammasat Hospital, situated in provincial Pathumthani in central Thailand. Participants were allocated into two groups, characterized by the severity of their obesity. Demographic data, body composition, along with resting energy expenditures were determined. Serum samples were collected for the metabolic profile and inflammatory markers. Fecal samples were obtained for gut microbiota analysis via 16S rRNA Illumina. The obese group exhibited notably greater relative abundance of Actinobacteriota in comparison to the severely obese group, along with a lower abundance of Bacteroidota. There were no statistically significant differences in the relative abundance of Firmicutes and the Firmicutes to Bacteroidota ratio between the two cohorts. Bacteroidota positively correlated with FMI, while Actinobacteriota showed a negative correlation with FMI.

The data gathered from this study illustrated that children and adolescents with obesity and severe obesity in Thailand showed differences in the relative abundance of Actinobacteriota and Bacteroidota. Certain microbiome taxa showed correlations with various body and metabolic parameters.

Boscalid (BO), one of the frequently detected fungicides of succinate dehydrogenase inhibitor in water environments, has unknown effects on the respiratory function and gut health of aquatic organisms. Therefore, zebrafish were exposed to BO solutions (0.01-1.0 mg/L) for 21 days to assess its effects on zebrafish respiration and intestinal microbiota in this study. The results showed that exposure to 0.1 and 1.0 mg/L BO for 21 days resulted in zebrafish exhibiting aggregation of gill filaments, reduction of mucous cells, and significantly decreased opercular movement, linked to a marked decline in the activity of respiratory chain complex II. 16S rRNA gene sequencing revealed significant changes in the intestinal microbiota composition of zebrafish exposed to 1.0 mg/L BO. Specifically, the relative abundance of beneficial bacteria (Cetobacterium) was markedly reduced, while pathogenic bacteria (such as Ralstonia, Legionella, Acinetobacter, Escherichia/Shigella) associated with energy metabolism and immune pathways in zebrafish showed a significant increase in relative abundance. Accordingly, metagenomic functional prediction analysis further revealed the potential impact of BO-induced gut microbiota changes on energy metabolism and immune pathways in zebrafish. Furthermore, histopathological analysis of intestinal tissues revealed that exposure to BO resulted in necrosis and shedding of epithelial cells, as well as a decrease in goblet cell count, which exacerbated adverse effects on intestinal health. In conclusion, sublethal exposure to BO affects the respiratory function and intestinal health of zebrafish. Therefore, the impact of BO in aquatic environments on fish health warrants attention.

This study aims to explore the potential causal relationship between gut microbiota and lung squamous cell carcinoma (LUSC).

A bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide association study (GWAS) data from gut microbiota and LUSC. Gut microbiota served as the exposure factor, with instrumental variables selected from a GWAS involving 18 340 participants. LUSC data were drawn from a European cohort including 29 266 LUSC cases and 56 450 controls. Inverse-variance weighted (IVW) method was used as the primary method, with the Benjamini-Hochberg method applied to adjust for multiple comparisons. An independent dataset (ieu-a-967, containing 3275 LUSC cases and 15 038 controls) was used for replication analysis to ensure robustness.

IVW analysis found that Butyricicoccus (OR = 0.79, 95% CI: 0.63-0.99, P = .042) and Coprobacter (OR = 0.85, 95% CI: 0.74-0.97, P = .018) were significantly protective against LUSC. In contrast, Victivallis (OR = 1.11, 95% CI: 1.00-1.23, P = .045) and Ruminococcus (OR = 1.28, 95% CI: 1.03-1.60, P = .028) increased LUSC risk. Replication analysis in the independent dataset confirmed significant associations for Ruminococcus and Coprobacter. No reverse causality or pleiotropy was detected.

This study provides evidence of a causal relationship between specific gut microbiota and LUSC risk, highlighting new microbial targets for potential prevention and treatment strategies in lung cancer. Key messages What is already known on this topic?  Previous studies have suggested potential links between gut microbiota composition and the development of various cancers, including lung cancer. However, the exact causal relationship between specific gut microbiota and lung squamous cell carcinoma (LUSC) has remained unclear. Traditional observational studies have struggled to determine the direction of causality due to confounding factors, making further investigation necessary through more robust methods such as Mendelian randomization (MR). What this study adds?  This bidirectional MR study provides novel genetic evidence indicating that certain gut microbiotas are causally associated with LUSC risk. Specifically, Butyricicoccus appears to reduce the risk of LUSC, while Victivallis increases the risk. These findings highlight the role of the gut-lung axis in LUSC and open up new avenues for exploring gut microbiota as potential modulators of lung cancer risk. How this study might affect research, practice, or policy?  The implications of this study may significantly influence future research into cancer prevention strategies by targeting gut microbiota. Additionally, it could inform clinical practices aimed at modulating gut microbiota to lower the risk of LUSC, potentially influencing dietary or probiotic interventions to reduce cancer susceptibility. Furthermore, these results might shape public health policies that focus on the gut-lung axis as a novel avenue for cancer prevention and management.

Spinal cord injury (SCI) leads to severe neurological dysfunction with significant nutritional alterations. These alterations are closely associated with gut dysbiosis and neurogenic gut dysfunction after SCI, creating complex interactions that further exacerbate metabolic disturbances and impede neurological recovery. In the context of SCI, diet not only fulfills basic nutritional needs but also serves as an important therapeutic tool to modulate these interactions. This review provides a broad overview of existing research findings, analyzes the impact of existing dietary interventions on SCI, and attempts to clarify the complex relationship between diet and host and gut microbiota. We hope to provide a clear direction for future research and a scientific basis for the development of personalized dietary interventions to improve the nutritional status of SCI patients, reduce the incidence of complications such as metabolic disorders, and promote the recovery of neurological function and overall quality of life of SCI patients. STATEMENT OF SIGNIFICANCE: This review evaluates the nutritional changes in patients with spinal cord injury, comprehensively elucidating the effects of dietary interventions on SCI patients from both the host and gut microbiota perspectives. By revealing the complex interactions among them, it lays the foundation for developing personalized nutritional intervention strategies to optimize recovery and improve long-term health outcomes in the future.

The gut microbiota, a substantial group of microorganisms residing in the human body, profoundly impacts various physiological and pathological mechanisms. Recent studies have elucidated the association between gut dysbiosis and multiple organ diseases. Gut microbiota plays a crucial role in maintaining gastrointestinal stability, regulating the immune system and metabolic processes not only within the gastrointestinal tract but also in other organs such as the brain, lungs, and skin. Dysbiosis of the gut microbiota can disrupt biological functioning and contribute to the development of metabolic disorders. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated proteins (Cas) modules are adaptive immune systems in numerous archaea and bacteria. CRISPR/Cas is a versatile gene-editing tool that enables modification of the genome in live cells, including those within the gut microbiota. This technique has revolutionized gene editing due to its simplicity and effectiveness. It finds extensive applications in diverse scientific arenas, facilitating the functional screening of genomes during various biological processes. Additionally, CRISPR has been instrumental in creating model organisms and cell lines for research purposes and holds great potential for developing personalized medical treatments through precise genetic alterations. This review aims to explore and discuss the possibilities of CRISPR/Cas and the current trends in using this technique for editing gut microbiota genes in various metabolic disorders. By uncovering the valuable potential of CRISPR/Cas in modifying metabolic disorders through the human gut microbiota, we shed light on its promising applications.

Lead is highly toxic to the developing brain. Given its persistence in the environment, new intervention strategies are needed to mitigate the impacts of lead on child neurodevelopment. The gut microbiome, referring to the bacteria and microorganisms residing in the gastrointestinal system, may be a viable target for intervention. This short review summarizes recent evidence linking the gut-brain axis to child developmental outcomes. We explore how lead-induced effects to the gut microbiome could indirectly affect child neurodevelopment, such that disrupting or offsetting this mediating process could buffer the effects of lead on child developmental outcomes. Unexpected findings with respect to child microbiota diversity and child cognitive and behavioral outcomes as well as lead exposure and adult microbiota diversity are discussed. When possible, we draw connections between observed changes to relative bacterial abundance, proposed bacterial functions, and downstream effects to brain development. We also explore how the gut microbiome might modify the toxicity of lead by impeding the uptake of lead across the gastrointestinal tract or through indirect mechanisms in such ways that the gut microbiome does not fit within a mediating pathway. In this case, promoting the buffering capacity of the gut microbiome may reduce the impacts of lead on child neurodevelopment. The goal of this short review is to bring attention to the potential role of the gut microbiome in the associations between lead exposure and child neurodevelopment with an eye towards intervention.

Non-digestible polysaccharides (NDPs) are a type of polysaccharides that are difficult for human digestive enzymes to degrade. They typically reach the large intestine as food residues and exert prebiotic effects by interacting with intestinal microorganisms. However, they were limited in practical application value due to their complex structure and poor water solubility. Hence, the alteration of the physicochemical properties of NDPs is of great significance for enhancing their functional performance. The existing literature on the modification of NDPs primarily focuses on chemical methods to modify their physicochemical properties. Meanwhile, we also found that they focus on the modification methods themselves, lacking a systematic summary and analysis of the regulation of intestinal microecological functions by modified NDPs. The correlation between the physicochemical properties of modified NDPs and the regulatory mechanisms of gut microbiota needs to be systematically summarized. Therefore, this paper aims to systematically review the modification methods of NDPs from the perspectives of physics, chemistry and biology, with a focus on the molecular mechanisms and optimization strategies of these modification methods, such as the combined use of various modification methods, the regulatory mechanisms of the modified NDPs on the microbiota, as well as their potential applications in functional foods and pharmaceutical carriers. This paper could provide a theoretical basis for the selective modification and targeted regulation of intestinal microecology by NDPs and the development of new functional NDPs products, which is of great significance for promoting the innovative application of NDPs in precision nutrition and adjunctive disease therapy.

Healthcare professionals face increasing challenges when managing older patients, a group characterized by significant interindividual variability in comorbidity patterns, homeostatic capacity, frailty status, cognitive function, and life expectancy. Complex therapeutic decisions may increase the risk of inappropriate polypharmacy, drug-drug, and drug-disease interactions in the context of age-associated pharmacokinetic and pharmacodynamic alterations, with consequent drug accumulation and toxicity.

This state-of-the-art narrative review article summarizes and critically appraises the results of original research studies and reviews published in PubMed, Scopus, and Web of Science, from inception to 9 April 2025, on age-associated changes in critical organs and systems and relevant pharmacokinetic and pharmacodynamic alterations. It also discusses the emerging role of frailty and the gut microbiota in influencing such alterations and the potential utility of machine learning techniques in identifying new signals of drug efficacy and toxicity in older patients.

The available knowledge regarding specific age-associated pharmacokinetic and pharmacodynamic alterations applies to a limited number of drugs, some of which are not frequently prescribed in contemporary practice. Future studies investigating a wider range of drugs and their patterns of use will likely enhance therapeutic efficacy and minimize toxicity in the older patient population.

Gut microbiota has a crucial role in the pathophysiology of metabolic-associated steatotic liver disease (MASLD), influencing various metabolic mechanisms and contributing to the development of the disease. Dietary interventions targeting gut microbiota have shown potential in modulating microbial composition and mitigating MASLD progression. In this context, the integration of multi-omics analysis and artificial intelligence (AI) in personalized nutrition offers new opportunities for tailoring dietary strategies based on individual microbiome profiles and metabolic responses. The use of chatbots and other AI-based health solutions offers a unique opportunity to democratize access to health interventions due to their low cost, accessibility, and scalability. Future research should focus on the clinical validation of AI-powered dietary strategies, integrating microbiome-based therapies and precision nutrition approaches. Establishing standardized protocols and ethical guidelines will be crucial for implementing AI in MASLD management, paving the way for a more personalized, data-driven approach to disease prevention and treatment.

Osteoporosis (OP) is the second most detrimental chronic disease, and thus novel diagnostic and therapeutic approaches are needed. In recent years, there has been an increased emphasis on the utilization of gut microbiota (GM) in the context of OP. However, a comprehensive bibliometric analysis on this subject is currently lacking. Furthermore, a deeper exploration of the role of GM in bone health is imperative, and there is a pressing need to foster international and inter-agency exchange and experience in this field. Accordingly, this study aimed to provide an overview of the research trends in this field and propose suggestions for related scientific and technological research and development.

The Web of Science database was searched for articles related to both GM and OP. Statistical analyses and data visualization were performed using the EXCEL and CiteSpace software.

China exhibited the highest number of publications, followed by the United States. NUTRIENTS and Sichuan University were identified as the journal and institution, respectively, with the highest number of articles. Notably, the keywords "gut microbiota" and "bone loss" have been increasingly used in publications.

In conclusion, this study fills the existing gap in the literature and contributes valuable insights to the understanding of the relationship between GM and OP.

Anthocyanins (Anthos; flower and kyanos; blue) are natural coloring compounds from the flavonoids class that include cyanidin, peonidin, delphinidin, malvidin, pelargonidin, and petunidin. Recently, the role of anthocyanins in disease prevention, especially inflammation, diabetes, cancer, neuro-disorders, hepato-renal protective, and immuno-modulation properties has been highlighted. The current review covered the literature on the pharmacokinetics and pharmacological effects of anthocyanins, especially absorption, distribution, metabolism, and excretion (ADME). The discussion on molecular mechanisms underlying their therapeutic effects is the limelight of the article. The GLUT1, GLUT3, SGLT1, SMCT1, and SMCT2 are the main carriers involved in the transportation of anthocyanins in the gastrointestinal tract. The anthocyanins exert their anticancer effects by reducing the expression of IL-6, IL-1β, TNF-β, COX-2, downregulation of NF-kB, EZH2, MDR1, Akt, and modulation of P13K/AKT and AMPK/mTOR pathways. The reduction in α-amylase and α-glucosidase and improved FFAR1 activity results in antidiabetic effects. The regulation of PGC-1α/NRF2/TFAM, p-PI3K/Akt/GSK3β, and Nrf2/HO-1 prevents neurodegeneration. The anthocyanins impose hepato-renal protective effects via ameliorating NLRP3 inflammasome, inhibiting MDA, GSSG, iNOS, HO-1, ICAM-1, β2-microglobulin, and MPO activity, and improved SOD, CAT, and GSH activity. Anthocyanins promote beneficial gut microbiota and enhance SCFA production, thus inhibiting pro-inflammatory markers. The immuno-modulatory impact of anthocyanins involves the reduction of CRP, P-selectin, C1q, and C4. Anthocyanins reduce LDL, VLDL, TGs, and TC via improved GBA and upregulation of ATP6 V0C, ZO-1, and ATG4D expression. The WHO/FAO suggested that 2.5 mg/kg/day of grape-skin extracts of anthocyanins are safe, and China recommended that 50 mg/day of anthocyanins are safe for consumption. In a nutshell, the multifaceted health benefits of anthocyanins make them promising candidates for disease prevention and therapeutic interventions.

traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.

to investigate the effect of gut microbiota and metabolites disorder on TBI injury.

16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.

fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.

rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.

our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.

There are significant structural differences between breast milk fat and the fat found in existing infant formulas, and these differences may partly explain the observed variations in growth and development between breastfed and formula-fed infants. This study used mice compared three groups: a control group (mixed vegetable oil), an OPO group (vegetable oil added with OPO), and a human milk fat substitute (HMFS) group formulated to match the fatty acid composition of breast milk. Compared to the control group and OPO group, HMFS-fed mice exhibited reduced body fat content and improved cognitive abilities. Lipidomics studies revealed that these differences in HMFS mice were associated with downregulation of hepatic glycerolipids and upregulation of glycerophospholipids and sphingolipids, facilitating the delivery of long-chain polyunsaturated fatty acids to the brain. Molecular investigations confirmed that HMFS reduces body fat accumulation by inhibiting endogenous fatty acid synthesis and promoting fatty acid β-oxidation, while changes in hepatic lipid profiles result from lipid molecule synthesis and interconversion. Metataxonomic studies demonstrated that HMFS reshaped the gut microbiota, including upregulating Akkermansia and downregulating Desulfovibrio and the Firmicutes/Bacteroidetes ratio, with strong correlations observed between the change of gut microbiota and responded lipids in liver. Overall, the breast milk's unique fatty acid distribution promotes organismal growth by modulating hepatic lipid metabolism, systemic lipid circulation, and gut microbiota. These findings underscore the nutritional benefits of breast milk fat structure and provide insights for the development of next-generation infant formulas.

The microbiota in humans consists of trillions of microorganisms that are involved in the regulation of the gastrointestinal tract and immune and metabolic homeostasis. The gut microbiota (GM) has a prominent impact on the pathogenesis of metabolic syndrome (MetS). This process is reciprocal, constituting a crosstalk process between the GM and MetS. In this review, GM directly or indirectly inducing MetS via the host-microbial metabolic axis has been systematically reviewed. Additionally, the specifically altered GM in MetS are detailed in this review. Moreover, short-chain fatty acids (SCFAs), as unique gut microbial metabolites, have a remarkable effect on MetS, and the role of SCFAs in MetS-related diseases is highlighted to supplement the gaps in this area. Finally, the existing therapeutics are outlined, and the superiority and shortcomings of different therapeutic approaches are discussed, in hopes that this review can contribute to the development of potential treatment strategies.

The gut microbiota features an abundance of diverse microorganisms and represents an important component of human physiology and metabolic homeostasis, indicating their roles in a wide array of physiological and pathological processes in the host. Maintaining balance in the gut microbiota is critical for normal functionality as microbial dysbiosis can lead to the occurrence and development of diseases through various mechanisms. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are non-coding RNAs that perform important regulatory functions for many processes. Furthermore, the gut microbiota and lncRNAs/circRNAs are known to interact in a range of both physiological and pathological activities. In this article, we review existing research relevant to the interaction between the gut microbiota and lncRNAs/circRNAs and investigate the role of their crosstalk in the pathogenesis of different diseases. Studies have shown that, the gut microbiota can target lncRNAs ENO1-IT1, BFAL1, and LINC00152 to regulate colorectal cancer development via various signaling pathways. In addition, the gut microbiota can influence mental diseases and lung tumor metastasis by modulating circRNAs such as circNF1-419, circ_0001239, circHIPK2 and mmu_circ_0000730. These findings provide a theoretical basis for disease prevention and treatment and suggest that gut microbiota-lncRNA/circRNA crosstalk has high clinical value.

The gut microbiota is amenable to early nutrition including micronutrients but intake above and below the recommendations commonly occur with unknown consequences. Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine found centrally and peripherally with diverse functions such as food intake regulation via the hypothalamic 5-HT receptor 2C (5-HTR2C). This study determined the impact of prenatal micronutrients on the gut microbiota and serotonergic system in offspring. Pregnant Wistar rats were fed either recommended vitamins (RV), high vitamins (HV), high folic acid with recommended choline (HFRC), or high folic acid with no choline (HFNC). Offspring were fed a high-fat diet for 12 weeks postweaning. HV, HFRC, and HFNC males and females had lower hypothalamic 5-HTR2C protein expression compared to RV. Brain 5-HT concentrations were lower but colon 5-HT concentrations were higher in HV and HFNC males and females and HFRC males compared to RV. Refeeding response after 5-HTR2C agonist was negatively correlated with hypothalamic 5-HTR2C protein expression in males and with brain 5-HT concentrations in females. Random forest revealed top bacterial taxa, which Lactococcus, Ruminococcus, Bacteroides, and Oscillospira showed significant correlations with refeeding response and concentrations of brain and colon 5-HT. In conclusion, excess or imbalanced prenatal consumption of micronutrients leads to gut microbiota-associated disturbances in the serotonergic system in offspring.

The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.

Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.

In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.

Developing treatments for age-related diseases requires cost-effective and efficient approaches. Nutrients and natural metabolites offer safer alternatives to synthetic drugs. Aging increases the need for solutions that protect health and repair cells. Recent studies show that nutrients and natural products reduce oxidative stress, regulate metabolism, and influence longevity-related genes. This review focuses on vitamins, minerals, antioxidants, and natural products that improve healthspan and combat aging. It also discusses challenges such as standardization, clinical validation, and regulatory approval. Finally, emerging trends, such as personalized nutrition and advanced delivery systems, highlight the potential of these metabolites for addressing aging.

Infertility poses a substantial societal and economic burden; however, current preventive strategies are limited. Recently, the relationship between gut microbiota and infertility has garnered increasing attention. The dietary index for gut microbiota (DI-GM) is a new index that reflects the diversity of the gut microbiota. However, its association with female infertility remains unclear.

This cross-sectional study included 3,053 women aged 18-45 years from the National Health and Nutrition Examination Survey (NHANES) database between 2013 and 2018. Infertility was defined based on responses to a questionnaire on reproductive health. The DI-GM score was calculated by averaging the intake from two 24-h dietary recall interviews. Weighted multivariable logistic regression, restricted cubic splines (RCS), and subgroup analyses were used to investigate the association between DI-GM and female infertility.

Based on self-reported data, 370 participants (12.12%) were classified as infertile. A higher proportion of participants with lower DI-GM scores experienced infertility. Multivariable logistic regression analysis indicated a negative association between DI-GM and the risk of female infertility, regardless of whether the independent variable was analyzed as a continuous variable or in quartiles in the fully adjusted model (Model 3, continuous variable: OR = 0.89, 95% confidence interval (CI): 0.80-0.98, p = 0.025; Q4 vs. Q1: OR = 0.63, 95% CI = 0.42-0.94, p = 0.032, p for trend = 0.013). The RCS curves demonstrated a non-linear relationship between the DI-GM scores and infertility risk. Subsequent subgroup analyses corroborated the robustness of these findings.

These findings suggest a non-linear relationship between DI-GM and the risk of infertility in females, with lower DI-GM scores associated with a higher risk of infertility.

The gut microbiome plays a vital role in human health, functioning as a metabolic organ that influences nutrient absorption and overall well-being. With growing evidence that dietary interventions can modulate the microbiome and improve health, this review examines whether healthcare systems should prioritize personalized microbiome-targeted therapies, such as probiotics, prebiotics, and microbiota transplants, over traditional pharmaceutical treatments for chronic diseases like obesity, diabetes, cardiovascular risk, and inflammatory conditions. A systematic review using Web of Science and Scopus databases was conducted, followed by a scientometric analysis. Key metabolic pathways, such as dietary fiber fermentation and short-chain fatty acid production, were explored, focusing on their impact on lipid and glucose metabolism. The interactions between microbial metabolites and the immune system were also investigated. Dietary interventions, including increased fiber and probiotic intake, show potential for addressing dysbiosis linked to conditions, such as type 2 diabetes, obesity, and autoimmune diseases. The review emphasizes the need to incorporate microbiome modulation strategies into clinical practice and research, calling for a multidisciplinary approach that integrates nutrition, microbiology, and biochemistry to better understand the gut microbiome's complex role in health.

The gut microbiome is a rich source of nutrients that are critical to the development and biology of eukaryotes. Transfer RNAs (tRNAs) are essential components of protein synthesis, and some chemical modifications to tRNA rely on the availability of microbiome-derived nutrients. In eukaryotes, the micronutrient queuosine (Q) is salvaged from the microbiome or diet and then incorporated into eukaryotic tRNA to influence the speed and efficiency of protein synthesis. Here, we examine the role of microbiome-derived Q in mosquito larval development and behavior. When mosquito larvae are grown with a microbiome incapable of synthesizing Q, there is a significant impact on tyrosine levels and processes, which correlate with defects in behavior and cuticle formation. Due to defects in movement and behavioral responses, Q-deficient larvae demonstrate impaired predator evasion, leading to higher instances of capture by predaceous beetle larvae. The broad effects of Q-deficiency in mosquito larvae highlight the importance of microbiome-derived nutrients for eukaryotic physiology and behavior.

The development of nucleic acid and protein drugs for oral delivery has lagged behind their production for conventional nonoral routes. Over the past decade, the evolution of DNA- and RNA-based technologies combined with the innovation of state-of-the-art delivery vehicles for nucleic acids has brought rapid advancements to the biopharmaceutical field. Nucleic acid therapies have the potential to achieve long-lasting effects, or even cures, by inhibiting or editing genes, which is not possible with conventional small-molecule drugs. However, challenges and limitations must be addressed before these therapies can provide cures for chronic conditions and rare diseases, rather than only offering temporary relief. Nucleic acids and proteins face premature degradation in the acidic, enzyme-rich stomach environment and are rapidly cleared by the liver. To overcome these challenges, various delivery vehicles have been developed to transport therapeutic compounds to the intestines, where the active compounds are released and gut microbiota and mucosal immune system also play an important role. This review provides a comprehensive overview of the promises and pitfalls associated with the oral route of administration of biologics, current delivery systems, applications of orally delivered therapeutics, and the challenges and considerations for translation of nucleic acid and protein therapeutics into clinical practice.

Polystyrene microplastics (PS-MPs) pose significant risks to honeybee health. However, how microplastics (MPs) adversely influence honeybee survival through the gut pathway, especially the metabolic processes, remains poorly understood. To conduct the experiment, the honeybees (Apis mellifera L.) were exposed to PS-MPs (0.5 μm and 5 μm) at environmental concentrations of 25 mg/L and 50 mg/L for 21 days. Results revealed that PS-MPs reduced honeybee survival rates and food consumption. The accumulation of PS-MPs in honeybee guts caused structural damage to gut walls and elevated oxidative stress levels. Additionally, PS-MPs altered gut microbial communities, with a decrease in Lactobacillus and an increase in Bartonella. Gut metabolomics analysis indicated that PS-MPs disrupted metabolic pathways, upregulated amino acid and carbohydrate metabolism, and downregulated alpha-linolenic acid and lipid metabolism. Our study offers important insights into the physiological effects of accumulated MPs on honeybees, highlighting the critical need for effective strategies to manage environmental pollutants.

A novel bacterial strain, MSB163, was isolated from the stool sample of a healthy mother, 4 weeks after giving birth via vaginal delivery. Taxonomic identification tools revealed that MSB163 belongs to the genus Bacteroides, but it is distinct from any currently known species. The closest related species is Bacteroides cellulosilyticus strain BFG- 250, with an average nucleotide identity (fastANI) of 94.51%. The genome length of MSB163 is 6,440,948 bp and the GC content 42.95%. Two plasmids were identified in the whole genome sequence. MSB163 is a Gram-negative, rod-shaped, non-motile anaerobic bacterium. The optimum growth conditions were at 37 °C, pH 7 and 0% (w/v) NaCl. The respiratory quinones were the menaquinones MK- 10 and MK- 11 and C15:0 ANTEISO was the major fatty acid. The predominant polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phospholipid. According to the taxonomic results and physiological analysis, strain MSB163 represents a novel species of the genus Bacteroides, for which we propose the name Bacteroides maternus, since the type strain was isolated from the stool sample of a mother. B. maternus type strain (MSB163) sequencing can be accessed under the biosample ID SAMN3953129 on NCBI. The strain was deposited on BCCM/LMG Bacteria Collection under the accession number LMG 33,374 and Leibniz Institut DSMZ GMBH under the accession number DSM 117,047.

Background: Fatigue is a frequently reported symptom in children undergoing cancer treatment. Prior research shows an inverse relationship between fatigue and physical activity. Less is known about fatigue's relationship with physical function or the underlying biological mechanisms of fatigue. This study explored associations among fatigue, physical function, and associated metabolites. Methods: Children (7-18 years) provided serum samples and self-reports of fatigue and lower extremity physical function (mobility) using Pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) surveys at two timepoints during cancer therapy. PROMIS scores were categorized as high/low per established cut points (high fatigue T >47.5; high physical function T >51.5). High-resolution liquid chromatography-mass spectrometry extracted 29 metabolites hypothesized a priori to be associated with fatigue or physical function. Descriptive statistics summarized PROMIS scores, and linear mixed effect models estimated metabolite associations adjusting for age, gender and steroid use. Results: Forty children participated (female, 53%; 7-12 years, 38%; 13-18 years 62%; Hodgkins Lymphoma, 33%; Acute Lymphoblastic/Lymphocytic Leukemia, 40%; Osteosarcoma, 10%; Other, 17%). Physical function and fatigue were inversely related: T1 (r = -0.64; p < .001) and T2 (r = -0.63; p < .001). One metabolite (indole-3-latic acid) differentiated between low and high fatigue. Five metabolites differentiated significantly between low and high physical function (4-Hydroxybenzoic acid, m-Coumaric acid, myoinositol, tryptophan, and tyrosine). Conclusions:These findings substantiate prior studies showing metabolites, particularly amino acids, significantly associated with fatigue and physical function. All significant metabolites were associated with the gut microbiome. Physical function was inversely corelated with fatigue providing another potential intervention for fatigue management.

The relationship between immune cells and colorectal cancer (CRC) development has been extensively studied; however, the mediating role of gut microbiota in this relationship remains poorly understood.

We utilized summary data from genome-wide association studies (GWAS) to analyze 731 immune cell phenotypes, 473 gut microbiota, and CRC-related data. A two-step mediation analysis was employed to identify mediating gut microbiota. The primary analysis method was inverse variance weighting (IVW), supplemented by MR-Egger, simple mode, weighted median, and weighted mode analyses. Robustness of the results was ensured through systematic sensitivity analyses.

Our analysis identified 13 immune cell phenotypes significantly associated with CRC, including 10 protective factors and 3 risk factors. Additionally, 13 gut microbiota showed significant associations with CRC, comprising 8 protective factors and 5 risk factors. Mediation analysis revealed that 4-gut microbiota (1 order, 1 family, 1 genus, and 1 unclassified) mediated the relationship between immune cells and CRC. For instance, unclassified CAG - 977 mediated the effects of FSC-A on NK and NKT %lymphocyte on CRC risk, with mediation proportions of 11% and 12.3%, respectively. Notably, 22.3% of the protective effect of EM CD8br %CD8br on CRC was mediated through order Francisellales.

This study provides evidence for a potential causal relationship between immune cells, gut microbiota, and CRC, highlighting the mediating role of specific gut microbiota. These findings offer new insights into the pathogenesis of CRC and may inform future therapeutic strategies.

Radiotherapy, a widely employed cancer treatment, often triggers diverse inflammatory responses such as radiation enteritis, pulmonary injury, pelvic inflammation, dermatitis, and osteitis. Dietary polyphenols have recently emerged as promising agents for mitigating radiation-induced inflammation. However, their clinical application faced challenges related to variable bioavailability, individual pharmacokinetics, optimal dosing, and limited clinical evidence. Current researches revealed the efficacy of bioactive small molecule polyphenols in addressing radiation-induced inflammation. In this review, along with a comprehensive examination of the etiology and categories of radiation-induced inflammatory conditions, the diversity of polyphenols and elucidating their anti-inflammatory mechanisms are explored. This study emphasizes the recent progresses in delivery systems for dietary polyphenols, aiming to enhance radioprotection effects. The optimized utilization of polyphenols, with a theoretical framework and reference guide, is of paramount relevance. Through diverse delivery mechanisms, the more effective and safer radioprotective strategies become achievable. This endeavor aspires to contribute to breakthroughs in the dietary polyphenols' application, significantly enhancing human health protection during radiotherapy. These comprehensive insights presented here also support (pre)-clinical practices in navigating the complexities of utilizing dietary polyphenols for radioprotection, fostering advancements in the field and improving patient outcomes.

The prevalence of allergic diseases [e.g., asthma, allergic rhinitis (AR), atopic dermatitis (AD)] has increased significantly in recent years, which is coincides with a shift in modern eating habits. The Mediterranean diet, due to its anti-inflammatory properties, may be beneficial in the prevention of allergic diseases. However, its effects on allergic diseases have not been sufficiently studied. We investigated the relationship between adherence to the Mediterranean diet and allergic diseases.

This study analyzed the relationship between adherence to the Mediterranean diet (using the modified Mediterranean diet score, mMED) and atopic dermatitis, asthma, and allergic rhinitis in 12,080 participants using data from the 2013-2016 Korean National Health and Nutrition Examination Survey (KNHANES). Multiple logistic regression analyses were used to control for confounding factors such as age, gender, education level, income, and lifestyle.

In multivariable adjusted models, participants with higher mMED had a significantly lower risk of developing AD (OR 0.57; 95% CI, 0.36-0.92; p trend = 0.0201). When stratified by sex, this risk reduction was more significant in females (OR 0.50; 95% CI, 0.27-0.96; p trend <0.05). Across mMED components, fish and peanut intake were negatively associated with the occurrence of AD and AR (OR 0.55; 95% CI, 0.40-0.76; p trend <0.05, OR 0.75; 95% CI, 0.65-0.87; p trend <0.05). There was no significant association between asthma and AR and mMED scores.

High adherence to the Mediterranean diet is associated with a lower prevalence of atopic dermatitis, especially in women. Fish and peanut intake have an important protective role against atopic diseases.

Inflammatory bowel disease (IBD) includes chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, characterized by impaired function of the intestinal mucosal epithelial barrier. In recent years, ferroptosis, a novel form of cell death, has been confirmed to be involved in the pathological process of IBD and is related to various pathological changes, such as oxidative stress and inflammation. Recent studies have further revealed the complex interactions between the microbiome and ferroptosis, indicating that ferroptosis is an important target for the regulation of IBD by the gut microbiota and its metabolites. This article reviews the significant roles of gut microbial metabolites, such as short-chain fatty acids, tryptophan, and bile acids, in ferroptosis in IBD. These metabolites participate in the regulation of ferroptosis by influencing the intestinal microenvironment, modulating immune responses, and altering oxidative stress levels, thereby exerting an impact on the pathological development of IBD. Treatments based on the gut microbiota for IBD are gradually becoming a research hotspot. Finally, we discuss the potential of current therapeutic approaches, including antibiotics, probiotics, prebiotics, and fecal microbiota transplantation, in modulating the gut microbiota, affecting ferroptosis, and improving IBD symptoms. With a deeper understanding of the interaction mechanisms between the gut microbiota and ferroptosis, it is expected that more precise and effective treatment strategies for IBD will be developed in the future.

High-altitude-adapted chickens harbor a unique gut bacteriome essential for their survival under extremely cold and hypoxic environment, however, little is known about their population and functional dynamics, limiting their application in poultry production. Hence, this study employed amplicon-based metagenomics to examine the gut bacterial diversity and their functional profile in two high-altitude-adapted chicken lines, e.g. LEHBRO-1 and LEHBRO-3. The results revealed significant variations in taxonomic abundance at the phylum level, with Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria predominating in LEHBRO-1, whereas Firmicutes, Proteobacteria, Bacteroidetes, Planctomycetes, and Actinobacteria predominated in LEHBRO-3. Genus-level diversity and Linear Discriminant Analysis Effect Size (LEfSe) biomarker analysis also substantiated the differences in the gut bacterial communities between the two chicken lines. Furthermore, functional profiling revealed enrichment of carbohydrate, nucleotide, lipid, amino acid, fatty acid, energy, and glycan metabolic pathways in the gut bacteriomes of these high-altitude chicken lines. The Statistical Analysis of Metagenomic Profiles (STAMP) for metabolic profiling identified a significant difference in purine and protein metabolism between these two chicken lines. These findings indicate the unique gut bacteriome and their functional diversity in high-altitude-adapted chickens, which would provide a foundation for future research on gut therapeutics to improve chicken health and productivity in high-altitude areas.

Gut microbiome influences host health and well-being. Co-occurring hosts may exchange disease-causing bacteria belonging to these microbial communities. Therefore, monitoring gut microbiota composition in wildlife and humans is paramount to prevent zoonotic diseases, thus protecting and strengthening public health. We characterized diversity and abundance of the gut microbiome bacterial component across mahouts (captive elephant trainers and handlers), their pachyderms, livestock and wild herbivores in and around Chitwan National Park (Nepal). Firmicutes and Bacteroidota were invariably the dominant phyla. In humans, the relative abundance of Firmicutes was higher, the alpha diversity lower and beta diversity different compared to other host categories. Livestock and wild herbivores displayed similar alpha and beta diversity due to the presence of Proteobacteria, Actinobacteriota and Verrucomicrobiota. Elephants had a higher alpha diversity, and a significant beta diversity compared to other mammals. Our results suggest that taxonomic affiliation and diet niche are the main drivers of gut microbiota composition. Nevertheless, Mycobacterium and other potentially pathogenic bacteria genera were detected in elephants and livestock other than wild herbivores. These findings shed light on microbiota sharing and interlinking in each environment, thereby highlighting the importance of conservation medicine to better our understanding of health in co-occurring host species.

The physiology of a transplanted kidney is affected from the moment it is separated from the donor. The risk of complications arising from surgery are highly associated with ischemic-reperfusion injury (IRI) due to the effects of hypoxia and oxidative stress during the procurement, preservation and reperfusion procedures. Hypoxia promotes the formation of reactive oxygen species (ROS) and it seems apparent that finding ways of optimising the metabolic milieu for the transplanted kidney would improve recovery and graft survival. Studies have demonstrated the benefits of nutrition and antioxidant compounds in mitigating the disturbance of energy supply to cells post-transplant and at improving long-term graft survival. Particularly in patients who may be nutritionally deficient following long-term dialysis. Despite the high incidence of allograft failure, a search of the literature and grey literature reveals no medical nutriti on therapy guidelines on beneficial nutrient intake to aid transplant recovery and survival. This narrative review aims to summarise current knowledge of specific macro and micronutrients and their effect on allograft recovery and survival in the perioperative period, up to 1-year post transplant, to optimise the metabolic environment and mitigate risk to graft injury.