Gut Microbiota Research Articles

Gut microbiota and neurosurgery: understanding the gut-brain axis in postoperative recovery

Gut microbiota and neurosurgery: understanding the gut-brain axis in postoperative recovery

Alterations of the gut commensal akkermansia muciniphila in patients with COVID-19

ABSTRACT Dysbiosis of gut microbiota is well established in coronavirus disease 2019 (COVID-19). While studies have attempted to establish a link between the gut commensal Akkermansia muciniphila (A. muciniphila) and COVID-19, the findings have been inconsistent and sometimes controversial. The intestinal microbial abundance information of COVID-19 patients was acquired and analysed from GMrepo database. Subsequently, A. muciniphila’s metabolites, target-genes, and metabolite-target relationships was extracted from GutMGene database. Lastly, coronascape module in Metascape database is used for gene annotation and enrichment analysis in various host cells and tissues after SARS-CoV-2 infection. The results indicated that, in comparison to the health people, A. muciniphila was significantly elevated in COVID-19 patients. This bacterium was found to be associated with heightened expression of IL-10, TLR2, TLR4, CLGN, CLDN4, TJP2, and TJP3, while concurrently experiencing a reduction in the expression of IL-12A and IL-12B in humans. The regulatory genes of A. muciniphila primarily enhance responses to viruses and cytokines, positively regulate cell migration, and control epithelial cell proliferation. Our study revealed a significant increase in the gut commensal A. muciniphila in COVID-19 patients. This bacterium can modulate host immune responses and may also serve as a probiotic with antiviral properties.

Lactobacillus rhamnosus GG Supernatant Improves GLP-1 Secretion Through Attenuating L Cell Lipotoxicity and Modulating Gut Microbiota in Obesity.

Obesity is associated with decreased secretion of glucagon-like peptide-1 (GLP-1), which may result from lipotoxic damage to L cells caused by elevated levels of free fatty acids (FFAs). Although the probiotic Lactobacillus rhamnosus GG (LGG) exhibits anti-apoptotic properties, its potential to protect L cells from lipotoxic damage remains uncertain. This study investigated the impact of LGG supernatant (LGGs) on NCI-H716 cells treated with palmitic acid (PA) to mimic lipotoxic injury, focusing on cell apoptosis and function. Transcriptome sequencing was used to explore the mechanism of the action of LGGs. Additionally, the effects of LGGs on body weight, glucose tolerance, GLP-1 secretion, and gut microbiota were assessed in a diet-induced obese mouse model. PA induced L cell apoptosis and decreased the level of prohormone convertase 1 (PC1) in a concentration- and time-dependent manner, leading to intracellular accumulation of proglucagon (GCG). LGGs significantly restored PA-induced downregulation of PC1, GCG accumulation, and cell apoptosis, mainly by inhibiting endoplasmic reticulum stress and downregulating the ATF3/Chop pathway. Overexpression of Chop or ATF3 partially reversed the protective effect of LGGs. Additionally, in the mouse model, LGGs improved obesity, insulin resistance, and glucose tolerance, and restored GLP-1 secretion, which may be related to LGGs' inhibition of the ATF3/Chop pathway in L cells, regulation of gut microbiota composition, and enhancement of short-chain fatty acid production. Overall, LGGs can ameliorate high-fat diet-induced impairment of GLP-1 secretion by inhibiting lipotoxicity-mediated damage through the ATF3/Chop pathway and modulating the gut microbiota.

Effect of electroacupuncture combined with Tuina therapy on gut microbiota in patients with knee osteoarthritis

Effect of electroacupuncture combined with Tuina therapy on gut microbiota in patients with knee osteoarthritis

Dietary inflammatory potential and its impact on gut microbiota in patients with mild cognitive impairment.

Diet can regulate systemic inflammation and the composition of the gut microbiota, which may play a significant role in the development of cognitive impairment. This study aims to explore the impact of inflammatory diets on gut microbes in patients with mild cognitive impairment (MCI) and to investigate the relationship between these microbes and cognitive function. Dietary inflammatory properties and gut microorganisms were analyzed using the energy-adjusted dietary inflammatory index (E-DII) and 16S rRNA in MCI patients. No significant differences in the diversity of the gut microbiota were observed among different E-DII groups. In the anti-inflammatory diet group, the gut microbiomes exhibited higher abundances of Christensenella and Oribacterium, while Streptococcus, Ruthenibacterium, Enterobacter, and Conservatibacter were significantly more prevalent in the pro-inflammatory diet group (P < 0.05). Specific oral and gut genera were found to be associated with MoCA, AVLT-LR, and STT-A scores (P < 0.05). A higher dietary inflammatory index was linked to lower overall cognitive function, as well as deficits in language, attention, and executive function. Additionally, specific gut microbial compositions were associated with cognitive performance.

Fermented Wheat Germ Ameliorates High-Fat Diet-Induced Maternal Obesity in Rats: Insights from Microbiome and Metabolomics.

Maternal obesity significantly increases the risk of adverse outcomes for the mother and fetus. Fermented wheat germ (FWG) has demonstrated the potential to improve metabolic disorders, yet its effects have not been explored in maternal obesity models. This study investigated the ameliorating impact of FWG in rats with maternal obesity, focusing on its mechanisms through biochemical, gut microbiome, and serum metabolomics analysis. The results demonstrated that FWG was more effective than wheat germ in reducing body weight gain and fat accumulation, improving glycolipid metabolism disorders, and alleviating inflammation. Specifically, FWG modulated the composition of gut microbiota by fostering the growth of beneficial bacteria (e.g., Corynebacterium) while suppressing genera associated with maternal obesity (e.g., Blautia, Akkermansia, Dorea_A, and Faecousia). Furthermore, FWG modified high-fat diet-induced metabolites, primarily affecting pyrimidine metabolism and amino acid metabolism. These findings suggest that FWG may serve as a promising dietary intervention for mitigating maternal obesity and improving pregnancy outcomes.

Extensively acquired antimicrobial-resistant bacteria restructure the individual microbial community in post-antibiotic conditions

In recent years, the overuse of antibiotics has led to the emergence of antimicrobial-resistant (AMR) bacteria. To evaluate the spread of AMR bacteria, the reservoir of AMR genes (resistome) has been identified in environmental samples, hospital environments, and human populations, but the functional role of AMR bacteria and their persistence within individuals has not been fully investigated. Here, we performed a strain-resolved in-depth analysis of the resistome changes by reconstructing a large number of metagenome-assembled genomes from the gut microbiome of an antibiotic-treated individual. Interestingly, we identified two bacterial populations with different resistome profiles: extensively acquired antimicrobial-resistant bacteria (EARB) and sporadically acquired antimicrobial-resistant bacteria, and found that EARB showed broader drug resistance and a significant functional role in shaping individual microbiome composition after antibiotic treatment. Our findings of AMR bacteria would provide a new avenue for controlling the spread of AMR bacteria in the human community.

Interplay between the gut microbiota, its metabolites and carcinogens.

The gut microbiota is a complex and dynamic community of microorganisms that reside in the gastrointestinal tract, playing a critical role in the host. It produces many metabolites, such as bile acids, which play an important role in the metabolism of the host. One area of particular interest is its involvement in the development and treatment of cancer. Carcinogens, which are substances known to promote cancer formation and development, are present in various sources in our daily lives, including cigarettes, barbecues, and moldy foods. The types, amounts, and metabolism of carcinogens have been closely linked to cancer risk, underscoring the importance of understanding their interplay with the gut microbiota. Numerous studies have demonstrated significant differences in the composition and function of the gut microbiota in individuals with cancer compared to healthy individuals. The gut microbiota and its metabolites have been shown to influence the metabolism of various carcinogens, thereby affecting cancer progression. While much attention has been paid to the relationship between the gut microbiota and cancer risk, the potential interplay between the gut microbiota and carcinogens has received less focus. This review aims to emphasize the importance of exploring the interplay between the gut microbiota with its metabolites and carcinogens in cancer development and therapy. By uncovering the mechanisms of the interplay, new approaches for cancer prevention and treatment can be developed.

Gut microbiota influences colorectal cancer through immune cell interactions: a Mendelian randomization study

BackgroundColorectal cancer (CRC) is the most prevalent malignant tumor of the digestive system globally, posing a significant threat to human health and quality of life. Recent studies have established associations between gut microbiota and immune cells with CRC; however, the mechanisms by which gut microbiota influence the development and progression of CRC through immune mediators remain poorly understood.MethodsWe conducted a two-sample, bidirectional Mendelian randomization analysis. We utilized 731 immune cell types and 473 gut microbial species along with colorectal cancer statistics from published summary statistics from genome-wide association studies (GWAS).The analysis employed several methodologies, including inverse variance-weighted (IVW) analysis, MR-Egger regression, the weighted median method, and both weighted and simple model approaches.Sensitivity analyses were performed to confirm the reliability of the Mendelian randomization results, and reverse Mendelian randomization was used to assess the overall impact of CRC on gut microbiota and immune cells.ResultsOur findings suggest a causal relationship involving nine immunophenotypes and five specific gut microbial taxa with CRC. Notably, the gut microbes Alloprevotella and Holdemania, along with immune cell types CD3 on CD28- CD8br and CD4 + T cells, demonstrated significant causal associations with CRC. Mediation analysis revealed that the association between Alloprevotella and CRC was mediated by CD4 + T cells, with a mediation effect of 6.48%. Additionally, Holdemania was found to mediate its association with CRC through CD3 on CD28- CD8br, exhibiting a mediation effect of 9.29%. Reverse Mendelian randomization did not indicate any causal effect of CRC on specific immune cells or gut microbiota. Two-sided sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy in our findings.ConclusionsThis comprehensive Mendelian randomization study enhances our understanding of the mechanisms by which gut microbiota affects CRC through immune cell interactions. Further investigations are warranted to unravel the underlying mechanisms linking gut microbiota, immune cells, and colorectal cancer.

Decreased Fecal Nicotinamide and Increased Bacterial Nicotinamidase Gene Expression in Ulcerative Colitis Patients.

Ulcerative colitis (UC) is significantly linked with gut microbiota, which is essential for maintaining gut health. Their metabolites mitigate gut inflammation and bolster barrier function. Among these metabolites, we focused on vitamin B3, which has been reported to improve the pathogenesis of UC in mice. This study aimed to compare fecal vitamin B3 and gut microbiota between non-UC and UC patients. We assessed fecal metabolites and gut microbiota in 71 UC patients (UC group) and 72 non-UC patients (non-UC group) matched by sex and age in 10-year intervals. Fecal samples were collected and metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Bacterial DNA was extracted for 16S rRNA gene sequencing. We analyzed fecal nicotinamide levels and gut microbiota composition, employing statistical adjustments for confounding factors. We found that the UC group exhibited significantly lower fecal nicotinamide levels and α-diversity (Shannon index) compared to the non-UC group. The relative abundance of bacterial genera such as Treponema, UCG-002, and Fusicatenibacter was decreased, while Sellimonas, Fournierella, and Oscillospira were increased in the UC group. Moreover, a negative correlation was observed between Sellimonas abundance and fecal nicotinamide levels in the UC group. Additionally, the UC group showed higher expression of a bacterial gene encoding nicotinamidase compared to the non-UC group. These findings suggest that gut microbiota dysbiosis contributes to reduced vitamin B3 metabolism in UC patients. The study highlights the potential of replenishing vitamin B3 metabolic pathways as a novel therapeutic approach for UC treatment.

Metagenomic and phylogenetic analyses reveal gene-level selection constrained by bacterial phylogeny, surrounding oxalate metabolism in the gut microbiota.

The gut microbiota is critical for neutralizing dietary toxins. Oxalate is a toxin commonly produced by plants to deter herbivory and is widely consumed in the human diet. Excess levels of systemic or urinary oxalate increase risk of multiple urologic and cardiometabolic diseases. The current study employed multiple amplicon-based and shotgun metagenomic methodologies, alongside comparative phylogenetic analyses, to interrogate evolutionary radiation surrounding microbial oxalate degradation within the human gut microbiome. In conservative genome-based estimates, over 30% of gut microbial species harbored at least one oxalate-handling gene, with the specific pathways used dependent on bacterial phylum. Co-occurrence analyses revealed interactions between specialist genes that can metabolize oxalate or its by-products, but not multi-functional genes that can act in more than one oxalate-related pathway. Specialization was rare at the genome level. Amplicon-based metagenomic sequencing of the oxalate-degrading gene, formyl-CoA transferase (frc), coupled with molecular clock phylogenetic analyses are indicative of rapid evolutionary divergence, constrained by phylum. This was corroborated by paired analyses of non-synonymous to synonymous substitutions (dN/dS ratios), which pointed toward neutral to positive selection. Sequence similarity network analyses of frc sequences suggest extensive horizontal gene transferring has occurred with the frc gene, which may have facilitated rapid divergence. The frc gene was primarily allocated to the Pseudomonodota phylum, particularly the Bradyrhizobium genus, which is a species capable of utilizing oxalate as a sole carbon and energy source. Collectively evidence provides strong support that, for oxalate metabolism, evolutionary selection occurs at the gene level, through horizontal gene transfer, rather than at the species level.IMPORTANCEA critical function of the gut microbiota is to neutralize dietary toxins, such as oxalate, which is highly prevalent in plant-based foods and is not degraded by host enzymes. However, little is known about the co-evolutionary patterns of plant toxins and the mammalian gut microbiota, which are expected to exhibit features of an evolutionary arms race. In the current work, we present molecular evidence that microbial genes for oxalate degradation are highly prevalent in humans, potentially driven by extensive horizontal gene transfer events. Phylogenetic analyses reveal that oxalate-degrading genes are under a positive selection pressure and have historically undergone rapid diversification events, which has led to diverse ecological strategies for handling oxalate by gut bacteria. Collectively, data shed light on potential evolutionary relationships between the diet and the gut microbiota that occur relatively independently of the mammalian host.

Consumption of only wild foods induces large scale, partially persistent alterations to the gut microbiome

The gut microbiome (GM) is implicated in human health and varies among lifestyles. So-called “traditional” diets have been suggested to promote health-associated taxa. However, most studies focused only on diets including domesticated foods. Historically, humans consumed only wild foods, which might uniquely shape GM composition. We explored the impact of a wild-food-only diet on GM, particularly whether it increases the presence of health-associated and/or “old friend” taxa, and if the alterations to GM are persistent or transient. One participant collected daily fecal samples and recorded daily food consumption over an eight-week period, the middle four weeks of which he consumed only wild foods. Samples were profiled by 16S rRNA sequencing, and oligotyping and network analysis were conducted to assess microbial co-occurrence patterns. A wild-food-only diet considerably alters the composition of the GM, and the magnitude of the changes is larger than that observed in other diet interventions. No new taxa, including “old friends” appeared; instead, the proportions of already-present taxa shifted. Network analysis revealed distinct microbial co-abundance groups restructuring across dietary phases. There is a clear successional shift from the pre-, during- and post-wild-food-only diet. This analysis highlighted structural and functional shifts in microbial interactions, underscoring diet’s role in shaping the gut ecosystem.

Characteristics and potential diagnostic value of gut microbiota in ovarian tumor patients

The gut microbiota is closely related to the occurrence and development of cancer. However, the characteristics of gut microbiota associated with ovarian tumors remain elusive. In this study, fecal samples were collected from healthy control (HC) group and patients with ovarian tumor (OT) or with other benign tumor (OBT) for 16s rRNA sequencing to determine differential flora in gut microbiota. The composition of gut microbiota in the OT group, including bacterial abundance and diversity, was significantly different form HC and OBT groups. In the OT group, Escherichia_Shigella was markedly higher than in the HC group, while Coprococcus, Fusicatenibacter, Butyricicoccus and Oscillibacter were significantly lower than in HCs. The abundance of Fusicatenibacter, Butyricicoccus, Coprococcus Parasutterella, and Anaerotruncus in the OBT group was distinctly higher than that in the OT group, while the Lachnospiracae_ND3007_group was significantly lower. In addition, in OT patients, ovarian cancer (OC) and benign ovarian tumor (BOT) patients also showed a unique composition of gut microbiota. The random forest model was designed using different bacteria. Compared with HCs, area under curve (AUC) values for BOT and OC groups were 0.77 and 0.86, respectively. These findings suggest that some gut microbiota such as Escherichia_Shigella show a certain ability to distinguish between healthy individuals and patients with OT.

Trehalose Acts as a Mediator: Imbalance in Brain Proteostasis Induced by Polystyrene Nanoplastics via Gut Microbiota Dysbiosis during Early Life.

As an emerging contaminant, nanoplastics have evolved into a global ecological issue. Studies have shown that nanoplastics induce neurotoxicity across species, however, the causal mechanism remains unknown. This study aimed to explore the mechanism underlying the neurotoxicity caused by polystyrene nanoplastics (PS-NPs) via microbiota-gut-brain axis in immature mice, which serve as a model of infants and young children who are at higher exposure risk to NPs. The results indicated that while only a minority of PS-NPs reached the brain after exposure, they still had significant neurotoxic effects, as reflected by abnormalities in behavior, biochemical marker levels and histopathology. Proteomics and quantification analyses revealed that a proteostasis imbalance mediated by lysosomal and proteasome dysfunction in the brain is the key reason for the induced neurotoxicity. Further, we confirmed the indirect role of gut microbiota in the neurotoxicity induced by PS-NPs through 16S rDNA analyses and fecal microbiota transplantation. Crucial bacterial species such as Eubacterium coprostanoligenes potentially act as indicators for gut dysbiosis after PS-NPs exposure. Notably, we first estimated the indirect effect of gut microbiota on neurotoxicity attributed to PS-NPs in immature mice as 39.20% by high-dimensional mediation analysis. Trehalose was identified as a mediator connecting the gut microbiota and the brain, and the crucial role of trehalose supplementation was highlighted in remodeling the brain proteostasis to alleviate the neurotoxicity in immature mice. These findings are expected to contribute to a deeper understanding of the risk assessment and health protection of the nervous system from exposure to PS-NPs early in life.

Associations between dietary index for gut microbiota and stroke, and the mediating role of inflammation: a prospective cohort study.

Background: There has been a growing focus on the link between diet, gut microbiota, and stroke. The dietary index for gut microbiota (DI-GM), a novel indicator reflecting the effect of diet on gut microbiota diversity, has not been extensively studied in relation to stroke. This study aimed to examine the association between DI-GM and stroke, and to explore the potential mediating role of inflammatory biomarkers. Methods: We included 124 943 participants from the UK Biobank without stroke at baseline. The DI-GM was calculated using 24-hour dietary assessments. Cox proportional hazard models were employed to analyze the longitudinal associations of DI-GM with stroke and its subtypes. Restricted cubic spline (RCS) and subgroup analyses were also performed. Additionally, mediation analyses were conducted to explore the potential mediating role of inflammatory biomarkers between DI-GM and stroke risk. Results: During a median follow-up of 11.08 years, 3741 participants experienced a stroke, including 1626 ischemic strokes and 536 hemorrhagic strokes. After adjusting for covariates in the main model, higher DI-GM was significantly associated with reduced risks of stroke (HR = 0.97, 95% CI, 0.95-0.99, P < 0.001) and ischemic stroke (HR = 0.96, 95% CI, 0.94-0.99, P = 0.008), but not hemorrhagic stroke. No significant non-linear association was observed in the RCS analysis. Mediation analyses indicated that inflammatory biomarkers, including C-reactive protein, neutrophils, monocytes, leukocytes, neutrophil-to-lymphocyte ratio, and INFLA-score, partially mediated the association, accounting for 2.82% to 10.40% of the total effect. Conclusions: Higher DI-GM was associated with a reduced risk of stroke, particularly ischemic stroke. This protective association may be partially mediated by reductions in serum inflammatory biomarkers.

Gut microbiota-derived glutathione from metformin treatment alleviates intestinal ferroptosis induced by ischemia/reperfusion

BackgroundIntestinal ischemia/reperfusion injury (IIRI) is a life-threatening condition caused by multiple organ and system failures induced by dysbiosis and gut leakage. Metformin has demonstrated efficacy in protecting against IIRI, although the precise role of the gut microbiota in the underlying mechanism is still ambiguous.MethodsThis study examined intestinal barrier function and ferroptosis-related parameters in mice with IIRI following treatment with metformin. Additionally, dirty cages and antibiotics were utilized to investigate the impact of the microbiota on the effects of metformin. The analysis included an assessment of the microbial composition of metformin-treated mice and the biosynthetic activity of specific metabolites.ResultsMetformin effectively reduced gut leakage induced by IIRI, as evidenced by decreased intestinal permeability and increased Occludin, ZO-1, Claudin-1, and MUC-1 expression. A decrease in the expression of the pro-ferroptotic proteins ACSL4, TFR1, and VDAC2/3 and a decrease in dihydroethidium (DHE) fluorescence, iron, malondialdehyde (MDA), and myeloperoxidase (MPO) were further observed in metformin-treated mice. In contrast, the damage to the GPX4/GSH system caused by IIRI was reversed after metformin treatment, as shown by increases in GPX4, SLC7A11, and GSH. The antiferroptotic effects of metformin were phenocopied by its fecal microbiota but were eliminated by antibiotic intake. 16S rRNA analysis revealed that the metformin-modulated gut microbiota was characterized by increased Lactobacillus murinus, which expressed higher levels of GshF that contributed to the mitigation of IIRI.ConclusionsMurine gut microbiota mediated the anti-ferroptotic effect of metformin on IIRI, and the resulting increase in microbial GSH synthesis could serve as a critical pathway for anti-IIRI.

The impact of dietary salt on the development of hypertension and gut microbiome dysbiosis in captive-bred vervet monkeys (Chlorocebus aethiops)

BackgroundThe study was designed to establish a hypertensive nonhuman primate model to evaluate the role of dietary salt intake on blood pressure levels and gut microbiome regulation. Sixteen adult vervet monkeys were selected and assigned into two groups (control and experimental). The control group was given a maintenance diet (100 g), whereas the diet of the experimental group was supplemented with 1.5 g/day of dietary salt in the mornings for six months (T0-T6), thereafter, the dose was increased to 2 g/day for additional six months (T9-T12). Blood and stool samples were collected for biochemical and 16 S ribosomal RNA gene sequencing.ResultsThe control group was borderline hypertensive (134.7/62.9 mmHg), whereas elevated blood pressure levels (171.3/81.3 mmHg) were observed at T12 indicating the experimental group to be salt sensitive. Furthermore, gut microbiome analysis showed two main phyla, Bacteroidetes and Firmicutes. However, there was no significant difference for alpha and beta diversity for both groups.ConclusionThese findings suggested that dietary salt intake (1.5–2 g/day) caused alterations in systolic blood pressure levels, chloride and alkaline phosphatase (ALP). However, these changes were not associated with gut microbiome dysbiosis even though significant changes were observed over time for the individual groups.

The gut microbiome controls reactive astrocytosis during Aβ amyloidosis via propionate-mediated regulation of IL-17.

Accumulating evidence implicates the gut microbiome (GMB) in the pathogenesis and progression of Alzheimer's disease (AD). We recently showed that the GMB regulates reactive astrocytosis and Aβ plaque accumulation in male APPPS1-21 AD model mice. Yet, the mechanism(s) by which GMB perturbation alters reactive astrocytosis in a manner that reduces Aβ deposition remain unknown. Here, we performed metabolomics on plasma from mice treated with antibiotics (abx) and identified a significant increase in plasma propionate, a gut-derived short chain fatty acid, only in male mice. Administration of sodium propionate reduced reactive astrocytosis and Aβ plaques in APPPS1-21 mice, phenocopying the abx-induced phenotype. Astrocyte-specific RNA sequencing on abx and propionate treated mice showed reduced expression of pro-inflammatory and increased expression of neurotrophic genes. Next, we performed flow cytometry experiments where we found abx and propionate decreased peripheral RAR-related orphan receptor-γ (Rorγt)+ CD4+ (Th17) cells and IL-17 secretion, which positively correlated with reactive astrocytosis. Lastly, using an IL-17 monoclonal antibody to deplete IL-17, we found that propionate reduces reactive astrocytosis and Aβ plaques in an IL-17-dependent manner. Together, these results suggest that gut-derived propionate regulates reactive astrocytosis and Aβ amyloidosis by decreasing peripheral Th17 cells and IL-17 release. Thus, propionate treatment or strategies boosting propionate production may represent novel therapeutic strategies for AD.

Investigating fecal microbiota transplants from individuals with anorexia nervosa in antibiotic-treated mice using a cross-over study design

Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.

The gut-liver axis plays a limited role in mediating the liver’s heat susceptibility of Chinese giant salamander

The Chinese giant salamander (CGS, Andrias davidianus), a flagship amphibian species, is highly vulnerable to high temperatures, posing a significant threat under future climate change. Previous research linked this susceptibility to liver energy deficiency, accompanied by shifts in gut microbiota and reduced food conversion rates, raising questions about the role of the gut-liver axis in mediating heat sensitivity. This study investigated the responses of Chinese giant salamander larvae to a temperature gradient (10–30 °C), assessing physiological changes alongside histological, gut metagenomic, and tissue transcriptomic analyses. Temperatures above 20 °C led to mortality, which resulted in delayed growth. Histological and transcriptomic data revealed metabolic exhaustion and liver fibrosis in heat-stressed salamanders, underscoring the liver’s critical role in heat sensitivity. While heat stress altered the gut microbiota’s community structure, their functional profiles, especially in nutrient absorption and transformation, remained stable. Both gut and liver showed temperature-dependent transcriptional changes, sharing some common variations in actins, heat shock proteins, and genes related to transcription and translation. However, their energy metabolism exhibited opposite trends: it was downregulated in the liver but upregulated in the gut, with the gut showing increased activity in the pentose phosphate pathway and oxidative phosphorylation, potentially countering metabolic exhaustion. Our findings reveal that the liver of the larvae exhibits greater thermal sensitivity than the gut, and the gut-liver axis plays a limited role in mediating thermal intolerance. This study enhances mechanistic understanding of CGS heat susceptibility, providing a foundation for targeted conservation strategies in the face of climate change.