Fecal Microbiota Research Articles

Difference in fecal and oral microbiota between pancreatic cancer and benign/low-grade malignant tumor patients

BackgroundSignificant gaps exist in understanding the gastrointestinal microbiota in patients with pancreatic cancer (PCA) versus benign or low-grade malignant pancreatic tumors (NPCA). This study aimed to analyze these microbiota characteristics and explore their potential use in distinguishing malignant pancreatic lesions.MethodsBetween September 2020 and May 2024, fecal and oral samples were collected from 121 patients undergoing surgical resection or diagnostic biopsy of pancreatic lesions, including 75 patients with PCA and 46 patients with NPCA, and 16s rRNA sequencing was performed. Random forest models based using fecal and oral microbiota data were developed to diagnose PCA and NPCA, with performance assessed using the leave-one-out cross validation method.ResultsThe Shannon index and PCoA analysis revealed significant differences in oral microbiota composition between PCA and NPCA (p < 0.001 and p = 0.001, respectively). Fecal microbiome richness differed significantly (p = 0.02), though composition similarity was noted (p = 0.238). LEfSe identified 16 and 23 genera with significant differences in fecal and oral microbiomes, respectively. Random forest classifiers based on fecal and oral microbiota achieved areas under the curves (AUCs) of 89.4% and 96.3%, respectively, for distinguishing PCA and NPCA. In the mucinous tumor cohort, oral and fecal microbiome classifiers outperformed CA19-9, yielding AUCs of 83.0% and 85.2%, respectively.ConclusionFecal and oral microbiota compositions were significantly different between PCA and NPCA patients. Random forest classifiers utilizing fecal and oral microbiota data effectively distinguish between benign or low-grade malignant and malignant pancreatic lesions.

Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.

Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.

Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.

Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.

Dysregulation of saliva and fecal microbiota as novel biomarkers of colorectal cancer

The aim of this study was to investigate the biomarkers of salivary and fecal microbiota in Colorectal cancer (CRC). Initially, the study scrutinized the microbial community composition disparities among groups. Utilizing Lasso analysis, it sifted through operational taxonomic units (OTUs) to pinpoint distinctive features. Subsequently, by intersecting feature OTUs across groups, it curated a set of core-shared OTUs and devised a corresponding network. Concluding with functional enrichment analysis, the research delved into the divergent biological functions of these microbial communities within the studied groups. Analysis revealed higher bacterial diversity in saliva compared to feces, with distinct differences at both phylum and genus levels. Feces primarily contained Firmicutes, while saliva was dominated by Bacteroidetes and Proteobacteria. Notably, Escherichia-Shigella and Fusobacterium in feces and Streptococcus in saliva showed increasing abundance from average to adenoma to colorectal cancer. Specific dominant flora was identified within and between groups, including CRC and adenomas across different stages. Seventeen core shared OTUs were identified, and networks of shared OTUs were constructed for each group. Functional enrichment analysis highlighted distinct microbial community functions among the groups. This study’s findings on characteristic OTUs in saliva and fecal samples offer valuable insights for distinguishing between healthy individuals, adenoma patients, and those with colorectal cancer. This study identified distinctive OTUs in saliva and feces to distinguish between healthy individuals, adenoma patients, and those with CRC, offering a valuable diagnostic reference.

Dietary Supplementation with Methylsulfonylmethane and Myo-Inosito Supports Hair Quality and Fecal Microbiome in Poodles

This study aimed to investigate the effects of dietary supplementation with methylsulfonylmethane (MSM) and myo-inositol (MI) on hair quality, fecal microbiota, and metabolome in poodles. Thirty-two adult poodles categorized based on initial body weight and sex were randomly assigned to four groups. These groups (designated the CON, MSM, MI, and MSM + MI groups) received a basal diet, the same diet supplemented with 0.2% MSM + 0% MI, the same diet supplemented with 0% MSM + 0.2% MI, or the same diet supplemented with 0.2% MSM + 0.2% MI, respectively. The study lasted for 65 days. During the entire study period, body weight, average daily weight gain, feed intake, energy intake, and fecal output were normal in all the animals and did not differ significantly among the treatment groups. Hair scale thickness was lower in the MI and MSM + MI groups than in the CON group on Day 65 (p &lt; 0.05). An amino acid analysis of the hair revealed higher sulfur content in the MI and MSM + MI groups on Day 65 than on Day 0 (p &lt; 0.05). Moreover, the poodles in the MSM, MI, and MSM + MI groups presented significantly lower levels of Proteobacteria_unclassified and Candidatus Phytoplasma than did those in the CON group. The relative abundance of Gammaproteobacteria_unclassified was greater in the MSM and MI groups than in the CON group (p &lt; 0.05). The MSM group presented a greater abundance of Glucerabacter than the CON group (p &lt; 0.05). Compared with those in the CON and MSM + MI groups, the abundances of Paramuribaculum and Hafnia in the MSM group were greater (p &lt; 0.05). The abundances of Enterobacter and Kineothrix were greater (p &lt; 0.05) in the MI group than in the CON and MSM + MI groups. The poodles in the MI group presented significantly greater abundances of Bacteroidales_unclassified, Halanaerobium, Mycobacterium, and Erysipelotrichaceae_unclassified than did poodles in the CON, MSM, and MSM + MI groups. Fecal metabolomics analysis revealed that MSM, MI, and MSM + MI treatment markedly affected carbohydrate metabolism. MSM + MI treatment also influenced lipid metabolism. These findings suggest that dietary supplementation with MSM and MI can improve the hair quality of poodles.

Effects of Fructus Aurantii Extract on Growth Performance, Nutrient Apparent Digestibility, Serum Parameters, and Fecal Microbiota in Finishing Pigs

This study investigated the effects of Fructus Aurantii extract (FAE) on growth performance, nutrient apparent digestibility, serum parameters, fecal microbial composition, and short-chain fatty acids (SCFAs) in finishing pigs. In total, 75 Duroc × Landrace × Yorkshire pigs (equally divided by sex), with an initial body weight of 79.49 ± 4.27 kg, were randomly assigned to three treatment groups. The pigs were fed either a basic diet (CON) or a basal diet supplemented with 500 mg/kg of FAE (FAE500) and 1000 mg/kg of FAE (FAE1000). The FAE1000 group exhibited a significantly higher final body weight (FBW) (p &lt; 0.05), and the average daily feed intake (ADFI) showed an increasing tendency in the FAE500 and FAE1000 groups (p = 0.056) compared to the CON group. Additionally, the inclusion of FAE resulted in the significantly higher apparent digestibility of crude ash (Ash), gross energy (GE), and crude protein (CP) (p &lt; 0.05), with a tendency to the increased digestibility of dry matter (DM) (p = 0.053). Dietary FAE supplementation led to elevated serum levels of reduced glutathione (GSH) and decreased levels of serum L-lactic dehydrogenase (LDH), along with a tendency to increase serum glucose (GLU) levels (p = 0.084). The FAE500 group demonstrated higher serum concentrations of motilin (MTL) and gastrin (GAS) (p &lt; 0.05), and a tendency for reduced serum glucagon-like peptide-1 (GLP-1) level (p = 0.055) compared to the CON group. Furthermore, alpha diversity analysis revealed that the FAE500 group significantly increased the Chao 1 and Observed_species indexes (p &lt; 0.05). Similarly, beta diversity analysis indicated that FAE feeding altered the fecal microbial structure (p = 0.083). Notably, compared with the control group, CF231, Pediococcus, and Mogibacterium displayed higher relative abundance in the feces of the FAE500 group, whereas Tenericutes showed a reduction in relative abundance (p &lt; 0.05). Additionally, the relative abundance of Tenericute was negatively correlated with the digestibility of DM, GE, Ash, and CP (p &lt; 0.05). Serum MTL and GAS levels correlated positively with the Coprococcus, Dorea, Pediococcus, and Mogibacterium relative abundances (p &lt; 0.05). Collectively, dietary FAE supplementation could enhance growth performance by boosting beneficial bacteria in feces, stimulating gastrointestinal hormone secretion, and improving nutrient digestibility.

Rol de la alteración del eje microbiota-intestino-hígado en la enfermedad hepática esteatósica asociada a disfunción metabólica

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of liver morbidity worldwide, including conditions such as hepatocellular carcinoma and the need for liver transplantation, with a particularly high prevalence in Latin America. The pathogenesis of MASLD is multifactorial, involving both genetic and environmental factors, including dysfunction of the gut-liver axis. The mechanisms involved in the progression of liver disease to cirrhosis are not yet fully understood. Recently, the intestinal microbiota has been recognized as playing a crucial role in disease progression by modulating systemic and hepatic inflammatory responses. In MASLD patients, microbial dysbiosis contributes to intestinal barrier dysfunction, increasing intestinal permeability and facilitating the translocation of microbial products to the liver, thereby exacerbating inflammation and hepatic damage. Additionally, alterations in bile acid levels and microbial metabolites further reinforce this pathological cycle. Therapeutic strategies aimed at restoring microbial balance—such as fecal microbiota transplantation, probiotics, prebiotics, and synbiotics—have shown promising results in modulating the microbiota-gut-liver axis and slowing MASLD progression. Further studies are needed to fully understand their impact on the pathophysiology of MASLD and to strengthen their integration into current therapeutic protocols for this disease.

Bacterial and host fucosylation maintain IgA homeostasis to limit intestinal inflammation in mice.

Inflammatory bowel disease is associated with several genetic risk loci. Loss-of-function mutation in the α1,2-fucosyltransferase (fut2) gene, which alters fucosylation on the surface of intestinal epithelial cells, is one example. However, whether bacterial fucosylation can contribute to gut inflammation is unclear. Here we show that host fucosylation status influences fucosylation biosynthesis by gut commensal bacteria. Mice colonized with faecal microbiota of Fut2 knockout mice or Bacteroides fragilis with lower surface fucosylation are predisposed to colitis. This was supported by human cohort data showing that bacterial fucosylation levels decrease in patients with inflammatory bowel disease and correlate with intestinal inflammation. Using a mouse model for Bacteroides fragilis to explore the role of fucosylation in gut immunity, we show that the fucosylation status of epithelial cells and bacteria is critical for maintaining B cell responses in the gut. Host-derived and dietary fucose mediate immunoglobulin A (IgA) recognition of gut microbiota, and this interaction facilitates the translocation of commensals to Peyer's patches and alters the immune landscape of Peyer's patches with increased germinal centre B cells and IgA-secreting antigen-specific B cells. Finally, dietary fucose enhances the IgA response against Salmonella and protects against systemic bacterial dissemination. This highlights the role of host and bacterial fucosylation in maintaining IgA homeostasis and immune escape mechanisms.

RS4 Type Resistant Starch Improves Type 2 Diabetes Mellitus in Mice by Interacting With Lactobacillus johnsonii

ABSTRACTRS4‐type resistant starches have been applied in food industry as thickeners or studied as functional foods for a long time. However, the influence and mechanism of RS4 on Type 2 diabetes mellitus (T2DM) have not been elucidated. In this study, sinapic acid starch ester (SASE) was chosen as a representative of functional RS4, and its anti‐diabetic activity and underlying mechanism were investigated. Results showed that SASE administration lowered blood glucose and ameliorated insulin resistance of streptozotocin‐induced diabetic mice via increasing serum butyrate level. Fecal microbiota transplantation confirmed the T2DM‐improving activity of SASE modulated gut microbiota. 16S rRNA gene sequencing indicated that SASE selectively promoted the proliferation of butyrate‐producing bacterium. In vitro co‐culture of promoted gut bacterium with SASE revealed that Lactobacillus johnsonii was one of the key bacteria in the degradation of SASE. In conclusion, RS4 could selectively promote gut bacteria and increase short‐chain fatty acid production to alleviate T2DM.

The effect of complementary foods on the colonic microbiota of weaning infants: a systematic review.

The transition from breastmilk to solid foods (weaning) is a decisive stage for the development of the colonic microbiota. However, little is known about how complementary foods influence the composition and function of the colonic microbiota in infants. This systematic review collected evidence of the effect of individual foods on the fecal microbiota of weaning infants (4-12 months old) using five databases: PubMed, CENTRAL, Scopus, Web of Science, and ScienceDirect. A total of 3625 records were examined, and seven randomized clinical trials met the review's eligibility criteria. Altogether, 983 participants were enrolled, and plant-based foods, meats, and dairy products were used as interventions. Wholegrain cereal increased the fecal abundance of the order Bacteroidales in the two included studies. Pureed beef increased the fecal abundances of the genus Bacteroides and the Clostridium XIVa group, as well as microbial richness in two of the three included studies. However, the conclusions of this review are limited by the small number of studies included. No conclusions could be drawn about the impact of complementary foods on fecal metabolites. Further clinical trials assessing the effect of dietary interventions on both fecal microbial composition and function are needed to fill this knowledge gap in infant nutrition.

SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.

Embryonic muscle fiber formation determines post-birth muscle fiber totals. The previous research shows SYISL knockout significantly increases muscle fiber numbers and mass in mice, but the mechanism remains unclear. This study confirms that the SYISL gene, maternal gut microbiota, and their interaction significantly affect the number of muscle fibers in mouse embryos through distinct mechanisms, as SYISL knockout alters maternal gut microbiota composition and boosts butyrate levels in embryonic serum. Both fecal microbiota transplantation and butyrate feeding significantly increase muscle fiber numbers in offspring, with butyrate inhibiting histone deacetylases and increasing histone acetylation in embryonic muscle. Combined analysis of RNA-seq between wild-type and SYISL knockout mice with ChIP-seq for H3K9ac and H3K27ac reveals that SYISL and maternal microbiota interaction regulates myogenesis via the butyrate-HDAC-H3K9ac/H3K27ac pathway. Furthermore, scRNA-seq analysis shows that SYISL knockout alone significantly increases the number and proportion of myogenic cells and their dynamics, independently of regulating histone acetylation levels. Cell communication analysis suggests that this may be due to the downregulation of signaling pathways such as MSTN and TGFβ. Overall, multiple pathways are highlighted through which SYISL influences embryonic muscle development, offering valuable insights for treating muscle diseases and improving livestock production.

Comparison of Fecal Microbiota and Metabolites Between Captive and Grazing Male Reindeer

The reindeer (Rangifer tarandus) is a circumpolar member of the Cervidae family, and has adapted to a harsh environment. Summer is a critical period for reindeer, with peak digestibility facilitating body fat accumulation. The gut microbiota plays a pivotal role in nutrient metabolism, and is affected by captivity. However, differences in the composition of the gut microbiota and metabolites between captive and grazing reindeer during summer remain poorly understood. Here, we conducted a comparative study of the fecal microbiota and metabolites between captive (n = 6) and grazing (n = 6) male reindeer, using full-length 16S rRNA gene sequencing and gas chromatography–time-of-flight mass spectrometry, respectively. Our results indicated that Prevotella, Phocaeicola, Papillibacter, Muribaculum, and Bacteroides were the predominant genera in the feces of reindeer. However, microbial diversity was significantly higher in captive reindeer compared to their grazing counterparts. Principal coordinate analysis revealed significant differences in the fecal microbiota between captive and grazing reindeer. In captive reindeer, the relative abundances of the genera Clostridium, Paraprevotella, Alistipes, Paludibacter, Lentimicrobium, Paraclostridium, and Anaerovibrio were significantly higher, while those of the genera Prevotella, Phocaeicola, Pseudoflavonifractor, and Lactonifactor were significantly lower. A comparison of predicted functions indicated that pathways involved in fat digestion and absorption, histidine metabolism, lysine biosynthesis, and secondary bile acid biosynthesis were more abundant in captive reindeer, whereas the pathways of fructose and mannose metabolism and propanoate metabolism were less abundant. An untargeted metabolomic analysis revealed that 624 metabolites (e.g., amino acids, lipids, fatty acids, and bile acids) and 645 metabolites (e.g., carbohydrates and purines) were significantly increased in the feces of captive and grazing reindeer, respectively. In conclusion, we unveiled significant differences in fecal microbiota and metabolites between captive and grazing male reindeer, with the results suggesting a potentially enhanced ability to utilize plant fibers in grazing reindeer.

Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn’s disease

In this letter, we commented on the article by Wu et al . We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn’s disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.

Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.

The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.

Effect of Hydrolyzed Frozen Meat on Diet Palatability, Apparent Digestibility, Immune Response, Fecal Microbiota, and Metabolome in British Shorthair Cats

Frozen meat is an important source of protein in pet food, and has attracted much attention in recent years. In this study, we compared the effect of meat meal (MM), frozen meat (FM), and hydrolyzed frozen meat (HFM) as ingredients in extruded pet food on its palatability and apparent digestibility, as well as its effects on the immune response, fecal microbiota, and metabolome of British shorthair cats. A total of 24 British shorthair cats were allocated to the MM, FM, and HFM groups according to body weight and gender. The palatability test lasted 4 days and the feeding test lasted 45 days. The results showed that the FM and HFM diets had better palatability than the MM diet (p &lt; 0.05) and significantly improved dry matter and crude protein digestibility (p &lt; 0.05). The serum IL-10 level was significantly higher in the HFM group compared to the MM and FM groups (p &lt; 0.05). The serum IgM levels were also found to be significantly higher in the FM group compared to the MM and HFM groups (p &lt; 0.05). The blood urea nitrogen/creatinine ratio was significantly lower in the HFM and FM groups than in the MM group (p &lt; 0.05). Cats fed HFM had a higher abundance of fecal Actinobacteria and Bifidobacterium and a lower content of Bacteroidota (p &lt; 0.05). Furthermore, serum metabolomics analysis revealed that the tryptophan (Trp) metabolism and bile acid metabolism were affected by HFM. Overall, FM and HFM were better for the cat’s health than meat meal, but they also have some potential risks.

In vitro colonic fermentation of fermented Radix Astragali by Poria cocos and anti-hyperuricemia mechanism based on network pharmacology and experiment verification

AimThis research aimed to probe the effects of fecal microbiota and Lactobacillus acidophilus on the metabolism of Radix Astragali (RA) and Poria cocos solid fermenting Radix Astragali (FRA). It further explores pharmacological effects of RA, Poria cocos, and FRA on HUA mouse model and the mechanisms in HUA treatment.MethodsFecal microbiota and Lactobacillus acidophilus were used to ferment FRA and RA in vitro to probe the impacts of microbiota on the metabolism of active compound. A HUA mouse model was used to carry out pharmacodynamic experiment of anti-hyperuricemia. Network pharmacology and molecular docking was utilized to elucidate the underlying mechanisms of RA and Poria cocos in the treatment of HUA.ResultsThe results indicated that astragaloside IV (AG IV), total saponins, and flavonoids continuously decreased in FRA and RA during 48 h fecal microbiota colonic fermentation. During Lactobacillus acidophilus fermentation, in FRA, the content of AG IV peaked at 12 h with a value of 1.14 ± 0.20 mg/g; total saponins and flavonoids reached the highest values of 136.34 ± 6.15 mg/g at 12 h and 6.35 ± 0.06 mg/g at 6 h; AG IV and total saponins reached the highest values 0.63 ± 0.05 mg/g and 115.12 ± 4.12 mg/g at 12 h and 24 h in RA, respectively; and total flavonoids consecutively decreased. The counts of Lactobacillus acidophilus increased significantly in FRA compared with RA. Pharmacodynamic outcomes revealed that FRA effectively reduced blood levels of uric acid (UA), triglycerides (TG), xanthine oxidase (XOD), alanine aminotransferase (ALT), and aspartate transaminase (AST) in HUA mice, exerting protective effects on the liver and kidney. Network pharmacology showed that there were 93 common targets for RA, Poria cocos, and HUA with the top five core targets tumor necrosis factor (TNF), signal transducer and activator of transcription 3 (STAT3), cysteinyl aspartate specific proteinase 3 (CASP3), jun proto-oncogene (JUN), and estrogen receptor 1 (ESR1). Molecular docking analysis revealed that AG IV, calycosin and formononetin bond well to the core targets.ConclusionThis research revealed the interaction of RA and FRA with fecal microbiota and Lactobacillus acidophilus, RA and Poria cocos were featured with multiple components, target points, and signaling pathways in HUA treatment, which provided fresh insights for further HUA therapeutics.

Factors for Treatment Failure After Fecal Microbiota Transplantation in Clostridioides difficile Infection

Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement &lt;7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate &lt;7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in &lt;8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment.

Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis

ABSTRACT Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.

Functional Analysis of TAAR1 Expression in the Intestine Wall and the Effect of Its Gene Knockout on the Gut Microbiota in Mice

Currently, the TAAR1 receptor has been identified in various cell groups in the intestinal wall. It recognizes biogenic amine compounds like phenylethylamine or tyramine, which are products of decarboxylation of phenylalanine and tyrosine by endogenous or bacterial decarboxylases. Since several gut bacteria produce these amines, TAAR1 is suggested to be involved in the interaction between the host and gut microbiota. The purpose of this present study was to clarify the TAAR1 function in the intestinal wall and estimate the TAAR1 gene knockout effect on gut microbiota composition. By analyzing public transcriptomic data of the GEO repository, we identified TAAR1 expression in enterocytes, enteroendocrine cells, tuft cells, and myenteric neurons in mice. The analysis of genes co-expressed with TAAR1 in enteroendocrine cells allows us to suggest the TAAR1 involvement in enteroendocrine cell maturation. Also, in myenteric neurons, we identified the co-expression of TAAR1 with calbindin, which is specific for sensory neurons. The 16S rRNA gene-based analysis of fecal microbiota revealed a slight but significant impact of TAAR1 gene knockout in mice on the gut microbial community, which manifests in the higher diversity, accompanied by low between-sample variability and reorganization of the microbial co-occurrence network.

Research advances in gut microbes and autism spectrum disorders

This paper concludes that recent research on the interrelationship between gut microbiota and autism spectrum disorder (ASD) has gained significant attention. The study found that the composition of the gut microbiota in ASD patients is often markedly different from that of the general population, particularly in the species and abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, which are frequently imbalanced. The imbalance in intestinal microorganisms not only affects gut health but also disrupts the neurological functions mediated by the gut-brain axis, exacerbating the behavioral and cognitive symptoms associated with ASD. In recent years, microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), have shown some promise. The use of probiotics and prebiotics can increase the proportion of beneficial flora in the gut of patients with ASD, helping to produce anti-inflammatory short-chain fatty acids, thereby improving neurological symptoms. Additionally, FMT, which involves transplanting gut microbes from healthy individuals into ASD patients, has demonstrated significant improvements in both gut and behavioral symptoms in several studies. However, due to the high individual variability among ASD patients, a single microbial intervention is not consistently effective across all individuals. Some patients respond well to probiotics or FMT, whereas others show limited symptom improvement. This variability may be attributed to each patient's unique microbiota composition, immune status, and metabolic profile. Therefore, further research is needed to identify biomarkers that can predict the effectiveness of microbial interventions, thereby enabling more precise and individualised therapies. This review aims to provide guidance for future research and to offer a theoretical foundation and data support for exploring microbial modulation as a potential treatment for ASD.