Gut Microbiota Function Research Articles

Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.

Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.

Gut-Skin Axis: Unravelling the Link Between Gut Microbiome and Chronic Kidney Disease-Related Skin Lesions.

It is well known that skin lesions are among the most common complications of chronic kidney disease (CKD), which significantly impact the patient's quality of life. Research has demonstrated that gut and skin lesions are closely interconnected and affect each other. This interaction is referred to as the "gut-skin axis" and the intestinal microbiota plays a critical role in this interaction. Changes in gut microbiota composition and function are associated with the development of skin diseases, which are part of the "gut-skin axis". Presently, preliminary results have been demonstrated in basic and clinical research on CKD skin lesions. With further research, the "gut-skin axis" theory can provide new ideas for treating CKD skin lesions and may become a potential treatment target.

Inulin alleviates atherosclerosis through improving lipid metabolism, inflammation, and gut microbiota in ApoE-knockout mice: the short-chain is more efficacious.

Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS. ApoE-/- mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content. The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality. These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

Mechanisms of epigallocatechin gallate (EGCG) in ameliorating hyperuricemia: insights into gut microbiota and intestinal function in a mouse model.

Epigallocatechin gallate (EGCG), a prominent bioactive compound found in tea, offers numerous health benefits. Previous studies have highlighted its potential in mitigating hyperuricemia. In this study, hyperuricemic mice induced by potassium oxonate (PO) were treated with EGCG or the anti-hyperuricemia medication allopurinol (AP) to investigate the mechanisms underlying their anti-hyperuricemic effects. The results demonstrated that both EGCG and AP significantly reduced serum uric acid (UA) levels. Further analysis revealed that EGCG promoted the expression of UA secretion transporter genes (Oat1 and Oct1) while inhibiting the expression of UA reabsorption transporter genes (Urat1 and Glut9) in the kidney. By 16S rDNA sequencing, EGCG, but not AP, was found to alter the composition of the gut microbiota. Notably, EGCG induced significant changes in the relative abundance of specific bacteria such as Lactobacillus, Faecalibaculum, and Bifidobacterium, which displayed high correlations with serum UA levels and UA-related gene expression. Metabolomic analysis suggested that EGCG-induced modifications in bacterial metabolites might contribute to the alleviation of hyperuricemia. Transcriptomic analysis of the intestinal epithelium identifies 191 differentially expressed genes (DEGs) in EGCG-treated mice, including 8 purine-related genes. This study elucidates the anti-hyperuricemic mechanisms of EGCG, particularly its influence on the gut microbiota and gene expression in the intestinal epithelium.

Human milk oligosaccharides and milk fat globule membrane reduce allergic reactions in mice through the modulation of gut microbiota and metabolic functions.

Human milk oligosaccharides (HMOs) and the milk fat globule membrane (MFGM) represent novel treatments for cow's milk allergy (CMA). They exhibit the beneficial attribute of diminishing nutrient damage when compared to conventional enzymatic digestion of milk proteins. However, the effects and mechanisms underlying the synergistic interaction between HMOs and the MFGM in allergy treatment remain unclear. Consequently, this study was undertaken to assess the protective properties of HMOs and the MFGM against CMA and to elucidate their potential mechanisms in a mouse model of β-lactoglobulin (BLG)-induced allergy. The findings demonstrated that HMOs and the MFGM could significantly reduce the allergy score and splenic index, and they diminished the levels of inflammatory mediators (total immunoglobulin E (IgE), specific IgE, histamine, and mMCP-1), while concurrently bolstering tight junctions (ZO-1, claudin-1, and occludin), and reducing intestinal permeability. Notably, HMOs and the MFGM exhibited optimal synergy. In addition, HMOs and the MFGM synergistically mitigated the immune response to Th2 overactivity in allergy by the promotion of Th1 and Treg cell responses, thereby suppressing the levels of inflammatory cytokines IL-4 and IL-5. Analysis of the gut microbiota and its metabolic activities revealed that HMOs and the MFGM increased the abundance of Lactobacillus and Butyricicoccus, leading to higher production of butyrate. Furthermore, these beneficial bacteria and the resultant butyrate also contributed to the suppression of allergy-associated bacterial populations such as Desulfovibrio and Rikenellaceae. In summary, HMOs and the MFGM acted in synergy to modulate inflammatory responses and ameliorate barrier damage, contributing to the mitigation of CMA, a process potentially linked to gut microbiota dynamics and the resultant butyrate metabolism. This effect may be related to the gut microbiota and its metabolic production of butyrate.

Miao sour soup alleviates DSS-induced colitis in mice: modulation of gut microbiota and intestinal barrier function.

Miao sour soup (MSS), a daily fermented food in Guizhou, China, is rich in microorganisms with various beneficial activities, including anti-inflammatory and antioxidant activities. However, the therapeutic effects of MSS on IBD remain unexplored. This study aimed to investigate the protective effect of MSS against colitis in mice. In this study, we examined the microbial community structure of MSS by metagenomic sequencing and also explored the protective effect of MSS on DSS-induced colitis in mice. We investigated the effects of MSS on intestinal inflammatory response and intestinal barrier function in mice. Finally, the changes in intestinal flora were analyzed based on the 16S rRNA gene sequencing results. Significantly, the experiment result shows that MSS ameliorated the severity of DSS-induced disease in mice by mitigating colitis-associated weight loss, reducing the disease activity index of IBD, alleviating colonic hemorrhagic lesions, increasing colon length, and improving colonic tissue damage. Moreover, MSS preserved intestinal barrier integrity and restored intestinal epithelial function in mice. Additionally, MSS modulated the structure and composition of the intestinal flora. Furthermore, MSS downregulated pro-inflammatory factors and attenuated the NF-κB p65 expression, thereby mitigating the inflammatory response. These findings highlight the protective effect of MSS against DSS-induced colitis, providing substantial scientific support for potential applications of MSS as a functional food.

Supplementation with a cranberry extract favors the establishment of butyrogenic guilds in the human fermentation SHIME system.

Background: Proanthocyanidins (PAC) and oligosaccharides from cranberry exhibit multiple bioactive health properties and persist intact in the colon post-ingestion. They display a complex bidirectional interaction with the microbiome, which varies based on both time and specific regions of the gut; the nature of this interaction remains inadequately understood. Therefore, we aimed to investigate the impact of cranberry extract on gut microbiota ecology and function. Methods: We studied the effect of a cranberry extract on six healthy participants over a two-week supplementation period using the ex vivo artificial fermentation system TWIN-M-SHIME to replicate luminal and mucosal niches of the ascending and transverse colon. Results: Our findings revealed a significant influence of cranberry extract supplementation on the gut microbiota ecology under ex vivo conditions, leading to a considerable change in bacterial metabolism. Specifically, Bifidobacterium adolescentis (B. adolescentis) flourished in the mucus of the ascending colon, accompanied by a reduced adhesion of Proteobacteria. The overall bacterial metabolism shifted from acetate to propionate and, notably, butyrate production following PAC supplementation. Although there were variations in microbiota modulation among the six donors, the butyrogenic effect induced by the supplementation remained consistent across all individuals. This metabolic shift was associated with a rise in the relative abundance of several short-chain fatty acid (SCFA)-producing bacterial genera and the formation of a consortium of key butyrogenic bacteria in the mucus of the transverse colon. Conclusions: These observations suggest that cranberry extract supplementation has the potential to modulate the gut microbiota in a manner that may promote overall gut health.

Dynamic response of different types of gut microbiota to fructooligosaccharides and inulin.

Fructooligosaccharides (FOS) and inulin are beneficial for human health. However, their benefits differ in individuals who consume prebiotics. Several factors contribute to this variation, including host genetics and differences in the gut microbiota. Bifidobacterium and Bacteroides are strong carbohydrate-utilizing bacteria in the gut, and the level of the Bacteroides/Bifidobacterium (Ba/Bi) ratio in the gut is closely related to the body's ability to utilize prebiotics. However, how to select the type of prebiotics more beneficial for populations with specific Ba/Bi backgrounds and the underlying regulatory mechanisms remain unclear. Here, we explored the dynamics of the gut microbiota and metabolic functions during the in vitro fermentation of FOS and inulin in two different groups: Bacteroides/Bifidobacterium high (H) and Bacteroides/Bifidobacterium low (L). This study revealed that the baseline Ba/Bi ratio had a greater impact on the gut microbiota compared to prebiotic species. Noticeable differences were observed between the two groups after prebiotic intervention, with the H group being more likely to benefit from the prebiotic intervention. Compared to the L group, the H group exhibited significantly higher microbial α-diversity; the co-abundance response group 1 (CARG1) members Ruminococcus gnavus and Blautia involved in the synthesis of propionic and butyric acids increased significantly, the abundance of pathogenic bacteria such as Escherichia Shigella decreased significantly, and the ability to degrade carbohydrates and synthesize fatty acids was greater. Regression modeling showed that the key microbiota could predict the short-chain fatty acid (SCFA) levels, with FOS associated with the ecological roles of CARG2 and CARG7 and inulin associated with CARG4, which provides the basis for the use of prebiotics in nutritional applications and the stratification of populations based on pertinent microbiota profiles to explain the incongruent health effects in human intervention studies.

Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.

Role of Intestinal Microbiota in the Pathogenesis of Colorectal Cancer: A Narrative Review

The human gut microbiota forms a biome and acts as a neglected organ, playing vital roles in organ integrity, metabolism, immunity, and homeostasis. Variations in the microbiome can lead to disease initiation. Research using bacterial sequencing of faeces and digestive tissues has focused on understanding the role of gut microbiota in cancer development, particularly Colorectal Cancer (CRC), Dysbiosis and modifications in the intestinal microbiota have been observed in CRC cases. Hypotheses like the alpha bug hypothesis and the driver-passenger model aim to explain the correlation between gut microbiota and CRC pathogenesis. The present article summarise the functions of gut microbiota, mechanisms involved in colorectal carcinogenesis, and discusses the clinical significance of gut microbiota in CRC screening and therapy

Natto alleviates hyperlipidemia in high-fat diet-fed mice by modulating the composition and metabolic function of gut microbiota

Natto has long been considered as a medical-food dual-use product with a hypolipidemic effect. Our study showed that natto was effective in reducing the levels of total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and increasing the level of high-density lipoprotein cholesterol (HDL-C) in the serum of hyperlipidemic mice. Metabolism analysis showed that natto could improve the levels of amino acid metabolites, reduce the contents of acylcarnitines, and reverse the levels of purine alkaloids, mainly involving the tricarboxylic acid (TCA) cycle and metabolism of amino acids. Moreover, natto increased beneficial gut microbiota (e.g., Lactobacillus, Faecalibaculum and Oscillibacter) and reduced pathogenic gut microbiota (e.g., Alistipes and Prevotellaceae-UCG-003). In conclusion, our findings suggest that natto-mediated changes in the gut microbiota and its related metabolites can support the prevention of high-fat diet (HFD)-induced hyperlipidemia, laying the theoretical foundation for the continued development of natto as a functional food.

Milk-derived Lactobacillus with high production of short-chain fatty acids relieves antibiotic-induced diarrhea in mice.

Antibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, and this has warranted research into alternative protocols. In this study, we investigated the potential therapeutic effects of three cohorts, Lactobacillus plantarum KLDS 1.0386, Lactobacillus acidophilus KLDS 1.0901 and a mixed strain of both, on intestinal inflammation, the intestinal mucosal barrier, and microbial community in mice with ampicillin-induced diarrhea. The results showed that Lactobacillus inhibited the activation of the TLR4/NF-κB signaling pathway, decreased the expression of pro-inflammatory cytokines, increased the expression of anti-inflammatory cytokines in the murine intestine, and alleviated the intestinal barrier damage and inflammation induced by ampicillin. In addition, Lactobacillus ameliorates intestinal epithelial barrier damage by increasing the expression of tight junction proteins and aquaporins. After Lactobacillus treatment, the diversity of gut microbiota increased significantly, and the composition and function of gut microbiota gradually recovered. In the gut microbiota, Bacteroidetes and Escherichia Shigella related to the synthesis of short-chain fatty acids (SCFAs) were significantly affected by ampicillin, while Lactobacillus regulates the cascade of the microbial-SCFA signaling pathway, which greatly promoted the generation of SCFAs. Collectively, Lactobacillus showed better results in treating AAD, especially in mixed strains.

Lactobacillus acidophilus CICC 6075 attenuates high-fat diet-induced obesity by improving gut microbiota composition and histidine biosynthesis.

This study aimed to investigate the potential anti-obesity efficacy of Lactobacillus acidophilus CICC 6075. The study analyzed fecal metagenomic data from 120 obese and 100 non-obese individuals. C57BL/6 mice on normal diet or high-fat diet (HFD) were treated with L. acidophilus CICC 6075 by daily oral gavage for 12 weeks, followed by evaluations of the obesity phenotype. Metagenomic analysis revealed depletion of L. acidophilus in obese individuals. Administration of L. acidophilus CICC 6075 attenuated excessive weight gain and fat accumulation and maintained the intestinal barrier in HFD-induced obese mice. Sequencing results showed that HFD hindered α- and β-diversity while reducing the relative abundance of Lactobacillus and norank_f_Muribaculaceae and significantly increasing the relative abundance of Ileibacterium. L. acidophilus CICC 6075 reversed these results and reduced the Firmicutes/Bacteroidetes ratio. Supplementation of L. acidophilus CICC 6075 enhanced histidine biosynthesis, inhibited the NF-κB pathway, and significantly reduced the expression levels of inflammatory factors in adipose tissue. These results indicate that L. acidophilus CICC 6075 alleviates HFD-induced obesity in mice by inhibiting the activation of the NF-κB pathway and enhancing gut microbiota functionality. This suggests that L. acidophilus CICC 6075 may be a good candidate probiotic for preventing obesity.

The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases.

The Aryl hydrocarbon receptor (AHR) is a cytosolic receptor and ligand-activated transcription factor widely expressed across various cell types in the body. Its signaling is vital for host responses at barrier sites, regulating epithelial renewal, barrier integrity, and the activities of several types of immune cells. This makes AHR essential for various cellular responses during aging, especially those governing inflammation and immunity. In this review, we provided an overview of the mechanisms by which the AHR mediates inflammatory response at gut and brain level through signals from intestinal microbes. The age-related reduction of gut microbiota functions is perceived as a trigger of aberrant immune responses linking gut and brain inflammation to neurodegeneration. Thus, we explored gut microbiome impact on the nature and availability of AHR ligands and outcomes for several signaling pathways involved in neurodegenerative diseases and age-associated decline of brain functions, with an insight on Parkinson's and Alzheimer's diseases, the most common neurodegenerative diseases in the elderly. Specifically, we focused on microbial tryptophan catabolism responsible for the production of several AHR ligands. Perspectives for the development of microbiota-based interventions targeting AHR activity are presented for a healthy aging.

Oreochromis niloticus gastrointestinal microbiota affected by the infection with Staphylococcus haemolyticus and Providencia vermicola, two emerging pathogens in fish aquaculture

The rapid intensification of tilapia aquaculture is associated with losses due to emerging pathogens. The gastrointestinal microbiota plays a vital role in the host's health by modulating the immune system and several physiological functions. Recent studies suggest that bacterial pathogens may deleteriously affect the microbiota structure. This study analyzed the effect of challenging tilapia with two emerging bacterial pathogens: Staphylococcus haemolyticus and Providencia vermicola, on the stomach and intestinal microbiota. Immediately after infection, fish started showing disease signs, tilapia infected with S. haemolyticus and P. vermicola registered 40 and 67% survival after seven days, while no mortality was reported in the control group during the trial. Amplicon libraries constructed by amplifying the V4 region of the 16S rRNA gene were analyzed. Proteobacteria was the most dominant phylum in the stomach and intestine of all infection groups. Staphylococcus haemolyticus infection disrupted both stomach and intestine microbiota. For instance, Bacteroidetes abundance increased while Proteobacteria dropped in the stomach of fish infected with S. haemolyticus. Both alpha and beta diversity indexes showed a clear differentiation of this group from the control and P. vermicola-infected fish. The microbiota of the stomach and intestine of this last group was also affected, although the effects were not as severe as in the case of the S. haemolyticus challenge. Results revealed that both emerging pathogens could lead to dysbiosis, affecting the functioning of the tilapia gut microbiota.

The honey bee gut microbiota: a review under the perspective of bees threatened by agrochemicals

Although it is very well known that bees play a key role in the stability of several ecosystems globally, anthropogenic activities causing environmental degradation, such as the use of agrochemicals, can ultimately lead to the extinction of native species, with severe ecological consequences. The advances in high throughput sequencing technologies and bioinformatics tools in the last decades have contributed to the understanding of the importance of the microbiome for the health of different animal species. However, there is a paucity of information on the effects of the exposition to agrochemicals on the microbial composition of honeybees and how this can compromise their health. In this systematic review article, we discuss the composition and biological function of native honeybee gut microbiota and how it can be possibly affected by agrochemicals, including antibiotics. We performed a systematic literature review focusing on the effect of agrochemical use on the gut microbiota of honey bees. A bibliographical survey was conducted from 1950 to 2023 in all available databases. We used the keywords “honey bees”, “microbiome” and “agrochemicals”. A total of 95 papers addressing this topic were selected, carefully checked and grouped into three categories: 1) The bee microbiome and its importance; 2) Functional roles of the bee gut microbiome; and 3) The problem of the anthropic actions that threaten the gut microbiome of bees. The present report can serve future studies addressing the complex ecological aspects of antimicrobial usage in agriculture and livestock in the scope of honeybee preservation.

Biotics in pediatrics: Separating hype from reality

The gut microbiota has gained significant attention in research and the media for its role in health and disease. Dysbiosis, an imbalance in gut microbiota composition and function, is increasingly recognized as a contributing factor in the development of various gastrointestinal and extraintestinal conditions. In this growing understanding, biotics (probiotics, prebiotics, synbiotics, and postbiotics) have become a significant industry in many countries. Aggressive marketing often creates confusion, contributing to a gap between hype and reality regarding the effective use of these biotics. This article offers a concise overview of the current consensus definitions for various types of biotics. It will also review existing evidence on the effectiveness of different biotics in preventing and treating diseases in the pediatric population. Doing so will separate the hype from the reality, providing a balanced view of the benefits and limitations of biotics in pediatric care.

Metabolites of the gut microbiota may serve as precise diagnostic markers for sarcopenia in the elderly.

Sarcopenia, a disease recognized by the World Health Organization, has posed a great challenge to the world in the current aging society. The vital role of the gut microbiome through the gut-muscle axis in sarcopenia is increasingly recognized. However, the working mechanisms by which the gut microbiota functions have not been fully explored in the multi-omics field. Here, we designed a cross-sectional study that recruited patients (n = 32) with sarcopenia and healthy old adults (n = 31). Diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia (AWGS) in 2019 criteria. Muscle mass was represented by appendicular skeletal muscle mass measured by using direct segmental multi-frequency bioelectrical impedance and muscle strength was evaluated using the handgrip strength. The Short Physical Performance Battery, the 5-time Chair Stand Test, and the 4-metre Walk Test were used to assess physical performance. Shotgun metagenomic sequencing was used to profile the gut microbiome in order to identify its construction and function. Metabolome based on untargeted metabolomics was applied to describe the features and structure of fecal metabolites. In clinical indexes including triglycerides and high-density lipoprotein cholesterol, we noted a significant decrease in triglycerides (TG) and a significant increase in high-density lipoprotein cholesterol (HDL-C) in patients with sarcopenia. Appendicular skeletal muscle mass of patients with sarcopenia was lower than the health group. Based on intestinal metagenomic and fecal metabolomic profiles, we found that the gut microbiome and metabolome were disturbed in patients with sarcopenia, with significant decreases in bacteria such as Bifidobacterium longum, Bifidobacterium pseudocatenulatum, and Bifidobacterium adolescentis, as well as metabolites such as shikimic acid. Also, we plotted supervised classification models at the species level of gut bacteria (AUC = 70.83-88.33) and metabolites (AUC = 92.23-98.33) based on machine learning, respectively. Based on the gut-muscle axis network, a potential mechanism is proposed along the gut microbiome - key metabolites - clinical index, that Phascolarctobacterium faecium affects appendicular skeletal muscle mass, calf circumference, handgrip strength, and BMI via Shikimic acid metabolites. This study elucidates the potential mechanisms by which the gut microbiome influences the progress of sarcopenia through metabolites and provides a meaningful theoretical foundation for reference in the diagnosis and treatment of sarcopenia.

Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis

Initially considered a “safe” substitute for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been extensively used in the production of fluoropolymers for several years, leading to its environmental ubiquity and subsequent discovery of its significant bio-accumulative properties and toxicological effects. However, the specific impact of HFPO-TA on females, particularly those who are pregnant, remains unclear. In the present study, pregnant mice were exposed to 0.63 mg/kg/day HFPO-TA from gestational day (GD) 2 to GD 18. We then determined the potential effects of exposure on gut microbiota and fecal metabolites at GD 12 (mid-pregnancy) and GD 18 (late pregnancy). Our results revealed that, in addition to liver damage, HFPO-TA exposure during the specified window altered the structure and function of cecal gut microbiota. Notably, these changes showed the opposite trends at GD 12 and GD 18. Specifically, at GD 12, HFPO-TA exposure primarily resulted in the down-regulation of relative abundances within genera from the Bacteroidetes and Proteobacteria phyla, as well as associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. With extended exposure time, the down-regulated genera within Proteobacteria became significantly up-regulated, accompanied by corresponding up-regulation of human disease- and inflammation-associated pathways, suggesting that HFPO-TA exposure can induce intestinal inflammation and elevate the risk of infection during late pregnancy. Pearson correlation analysis revealed that disturbances in the gut microbiota were accompanied by abnormal fecal metabolite. Additionally, alterations in hormones related to the steroid hormone biosynthesis pathway at both sacrifice time indicated that HFPO-TA exposure might change the steroid hormone level of pregnant mice, but need further study. In conclusion, this study provides new insights into the mechanisms underlying HFPO-TA-induced adverse effects and increases awareness of potential persistent health risks to pregnant females.

Microencapsulated Limosilactobacillus reuteri Encoding Lactoferricin-Lactoferrampin Targeted Intestine against Salmonella typhimurium Infection.

Salmonella enterica serovar Typhimurium (S. typhimurium) is an important foodborne pathogen that infects both humans and animals and develops acute gastroenteritis. As porcine intestines are relatively similar to the human ones due to their relatively similar sizes and structural similarity, S. typhimurium causes analogous symptoms in both. Novel strategies for controlling S. typhimurium infection are also desired, such as mucosal-targeted delivery of probiotics and antimicrobial peptides. The bovine lactoferricin-lactoferrampin-encoding Limosilactobacillus reuteri (LR-LFCA) strain improves intestinal barrier function by strengthening the intestinal barrier. Weaned piglets were selected for oral administration of microencapsulated LR-LFCA (microcapsules entrap LR-LFCA into gastro-resistant polymers) and then infected with S. typhimurium for 3 days. We found that orally administering microencapsulated LR-LFCA to weaned piglets attenuated S. typhimurium-induced production of inflammatory factors in the intestinal mucosa by inhibiting the nuclear factor-kappa B (NF-κB) and P38 mitogen-activated protein kinases (MAPK) signaling pathway. Moreover, microencapsulated LR-LFCA administration significantly suppressed the oxidative stress that may correlate with gut microbiota (reduced Salmonella population and increased α-diversity and Lactobacillus abundance) and intestinal function (membrane transport and metabolism). Our work demonstrated that microencapsulated LR-LFCA effectively targeted intestine delivery of Lactobacillus and antimicrobial peptides and modulated gut microbiota and mucosal immunity. This study reveals a novel targeting mucosal strategy against S. typhimurium infection.