Investigating immune-modulatory function of α-glucopyranose-rich compound polysaccharides by MC38-N4/OT-I co-culture system.

The potential antitumor function of polysaccharides is well accepted, it is unclear whether polysaccharides have immunoregulatory effect on CD8+ T lymphocyte cells to attack tumor cells. To evaluate the CD8+ T function enhancing role of polysaccharide compounds, the MC38-N4/OT-I co-culture system was established. The synergistic and complementary immune effect of α-glucopyranose-rich compound polysaccharides can be achieved by manipulating the antigen-specific T-cell expansion capacity and efficacy. This study was designed to investigate the antitumor-enhancement activity of a α-glucopyranose-rich compound polysaccharides by determining the activation of CD8+ T cells in a co-culture system. Compared to the control group (42.5 % ± 0.72 %), the specific α-glucopyranose-rich compound polysaccharides, comprising Agaricus blazei Murill, Grifola frondosa and Pericarpium Citri Reticulatae, demonstrated a significant decrease (20.4 % ± 1.23 %, p < 0.05) in the survival rate of MC38-N4 cells in the co-culture system. Additionally, the α-glucopyranose-rich compound polysaccharides resulted in a substantial increase (p < 0.01) in the proportion of CD8+ T cells and CD62L+ central memory T cells, which is a less differentiated T cell subset with high immune activity. Collectively, we reported that specific polysaccharide combination, which remodel the function of cytotoxic T cells and provided a basis for improving immune functions by using the specific types of polysaccharides.

Prognostic value of anthropometric- and biochemistry-based nutrition status indices on blood chemistry panel levels during cancer treatment.

Body weight, body mass index (BMI), Nutrition Risk Screening 2002 (NRS2002), and prognostic nutritional index (PNI) are among vital nutrition status indices employed during cancer treatment. These have also been associated with levels of blood chemistry panels (BCPs), which are touted as significant indicators of disease prognosis. However, it remains unclear which nutrition status index better predicts future trends in specific BCPs. Using the records of 407 cancer patients, we retrospectively examined the potential of nutritional status indices at baseline for predicting changes in specific BCPs over a 6-week period. Generally, both serum biochemical parameters and nutrition status indices fluctuated over the study period among study participants. PNI was often linearly associated with blood cell counts (white blood cells [WBCs] and hemoglobin) compared with anthropometric-based nutrition status indices. Increase in body weight was protective against having abnormal lymphocyte levels at 6 weeks (odds ratio [OR]: 0.960-0.974; CI: 0.935-0.997; P < 0.05), while increase in baseline PNI was associated with 0.865-0.941 and 0.675-0.915 odds of having future abnormal WBC and lymphocyte levels, respectively. Increases in PNI were also protective against having future abnormal albumin levels (OR: 0.734-0.886) and 8.5-12.5% decreases in the odds of having an abnormal C-reactive protein level in subsequent visits. Changes in NRS2002 tended to be associated with the odds of having future abnormal blood glucose levels. In conclusion, the serum biochemistry-derived nutrition status index, PNI, is a more consistent measure as an early indicator to track the trends of future changes in the BCPs of cancer patients. This implies that PNI could be targeted as an early-warning measure with relevant preventive interventions for patients at risk of malnutrition.

A Water Polysaccharide-Protein Complex from Grifola frondosa Inhibit the Growth of Subcutaneous but Not Peritoneal Colon Tumor under Fasting Condition.

SCOPE: Grifola frondosa has been shown to induce immune modulatory, modulate autophagy, and apoptosis in cancer cells. However, little is known about its potential for managing tumor progression as an adjunct to nutrient restriction. METHODS AND RESULTS: Water extract produces a G. frondosa polysaccharide-protein complex (G. frondosa PPC) of average molecular weight of 46.48 kDa, with glucose (54.8%) as the main constituent. Under serum-restricted conditions, G. frondosa PPC can significantly inhibit MC38 colorectal tumor cell migration in vitro. Under alternate-day fasting condition, G. frondosa PPC can only significantly inhibit the growth of subcutaneous (s.c.) tumor, but is feeble in halting its spread in the intraperitoneal (i.p.) cavity in tumor-bearing mice. Histopathological examination and Raman imaging show a significant increase in lipid content in the tumor microenvironment (TME) tissue of the s.c. tumor-bearing mice. G. frondosa PPC significantly increases C17:0 and C24:0 saturated fatty acids and significantly decreases C16:1 and C18:1 monounsaturated fatty acids in the TME of s.c. tumor-bearing mice compared with the i.p. cavity model. CONCLUSION: G. frondosa PPC significantly inhibits tumor growth in s.c. tumor-bearing mice under intermittent fasting conditions by altering the fatty acid composition of the TME.

Soy Peptide Supplementation Mitigates Undernutrition through Reprogramming Hepatic Metabolism in a Novel Undernourished Non-Human Primate Model.

In spite of recent advances in the field of undernutrition, current dietary therapy relying on the supply of high protein high calorie formulas is still plagued with transient recovery of impaired organs resulting in significant relapse of cases. This is partly attributed to the inadequacy of current research models in recapitulating clinical undernutrition for mechanistic exploration. Using 1636 Macaca fascicularis monkeys, a human-relevant criterion for determining undernutrition weight-for-age z-score (WAZ), with a cutoff point of ≤ -1.83 is established as the benchmark for identifying undernourished nonhuman primates (U-NHPs). In U-NHPs, pathological anomalies in multi-organs are revealed. In particular, severe dysregulation of hepatic lipid metabolism characterized by impaired fatty acid oxidation due to mitochondria dysfunction, but unlikely peroxisome disorder, is identified as the anchor metabolic aberration in U-NHPs. Mitochondria dysfunction is typified by reduced mito-number, accumulated long-chain fatty acids, and disruption of OXPHOS complexes. Soy peptide-treated U-NHPs increase in WAZ scores, in addition to attenuated mitochondria dysfunction and restored OXPHOS complex levels. Herein, innovative criteria for identifying U-NHPs are developed, and unknown molecular mechanisms of undernutrition are revealed hitherto, and it is further proved that soypeptide supplementation reprogramed mitochondrial function to re-establish lipid metabolism balance and mitigated undernutrition.

Identification of the Wound Healing Activity Peptidome of Edible Bird's Nest Protein Hydrolysate and the In Silico Evaluation of Its Transport and Absorption Potential in Skin.

In this study, edible bird's nest (EBN) was proven to be a suitable source of bioactive peptides via enzymatic hydrolysis. The ultrafiltration component of the EBN peptides (EBNPs, Mw < 3 000 Da) could be responsible for moderate moisture retention and filaggrin synthesis. It was found that EBNP had a great capacity to protect HaCaT keratinocytes from DNA damage caused by UVB-irradiation and enhance wound healing by increasing the migratory and proliferative potential of cells. Furthermore, the external application of EBNP could effectively repair high glycolic acid concentration-induced skin burns in mice. A total of 1 188 peptides, predominantly the hydrophobic amino acids (e.g., Leu, Val, Tyr, Phe), were identified in the EBNP by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Molecular docking showed that hydrophobic tripeptides from EBNP had a good binding affinity to proton-dependent oligopeptide transporter PepT1. Our data indicated that the hydrophobic amino acid-rich EBNP plays an important role in skin wound healing.

Peptides with Charged Amino Acids Mitigate nZnO-Induced Growth Inhibition of Lactobacillus rhamnosus LRa05.

Growing concern is about the potential side effects of nanomaterials from food packaging, notably zinc oxide nanoparticles (nZnO). Previous research revealed that walnut-derived peptides could mitigate this inhibitory effect, but the mechanism involved is unclear. Here, we found that not all peptides have such an effect. Based on the growth inhibition model of Lactobacillus rhamnosus LRa05 induced by nZnO, we assessed the protective effects of various peptides. Notably, four peptides containing charged amino acids (PPKNW, WPPKN, ADIYTE, and WEREEQE) were found to effectively alleviate the growth inhibition phenomenon. We hypothesize that the peptide-nZnO interaction modifies this effect, as confirmed through infrared, Raman, and fluorescence spectroscopy. Our results highlight amide bonds, amino groups, carboxyl groups, and benzene rings as key peptide binding sites on nZnO, with static quenching primarily due to hydrogen bonds and van der Waals forces. This study elucidates peptide characteristics in nZnO interactions, facilitating a deeper exploration of food matrix-nanocomposite interactions.

Intestinal absorptivity-increasing effects of sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate on food-derived bioactive peptide.

Delivering bioactive peptides orally is hampered by poor absorption across the gastrointestinal barrier. Using the walnut-derived peptide PW5, PPKNW, we explored whether coformulation of peptides with absorption enhancer sodium N-[8-(2-hydroxybenzoyl)aminocaprylate] (SNAC) could improve the intestinal absorption of orally-administered bioactive peptides. Herein, the application of SNAC enhanced the absorption efficiency of PW5 in a non-everted gut sac model. Particle size distribution (1 027.8 ± 6.74 nm) and zeta potential (-2.89 ± 0.07 mV) of the PW5-SNAC complex were significantly greater than that of individual PW5 and SNAC. Scanning electron microscopy revealed that SNAC application could aggravate the surface roughness and reduce the compact structure of PW5. It further showed that PW5 and SNAC binds through an endothermic process underpinned by hydrogen bond and van der Waals forces and that SNAC could bound primarily to the internal calyx of PW5. These findings are helpful for the effective delivery of bioactive peptides.

Hericium erinaceus mycelium-Derived Polysaccharide Alleviates Ulcerative Colitis and Modulates Gut Microbiota in Cynomolgus Monkeys.

SCOPE: Ulcerative colitis (UC) is rapidly increasing worldwide but prolong use of available corticosteroids treatment is associated with numerous adverse effects. There is the urgent need to develop novel therapeutic options. However, this requires the use of suitable disease models, but current models are generated with chemical agents mainly in rodents, which are unable to recapitulate the human occurrence. The aim of this study is to validate the occurrence of spontaneous UC in cynomolgus monkeys and explore the potential of Hericium erinaceus mycelium-derived polysaccharide in reversing UC pathologies. METHODS AND RESULTS: Postmortem bowel evaluation and biochemical analysis including inflammatory markers and fecal occult blood testing (FOBT) as well as nutrition status parameters, confirm the non-artificial induced spontaneous occurrence of UC in cynomolgus monkeys. Subsequently, H. erinaceus mycelium-derived polysaccharide supplementation significantly attenuates UC pathologies, improves nutritional status, reduces the incidence of diarrhea, and reduces inflammation in UC monkeys. Importantly, the polysaccharides administration enhances intestinal function and reshapes the gut microbiota. CONCLUSION: The study confirms the spontaneous UC monkeys can closely mimic the occurrence of UC in humans. Moreover, H. erinaceus mycelium-derived polysaccharide can effectively restore UC in monkeys, which show the prospects as precision nutritional supplement for the management of UC.

Bioactivity guided isolation and identification of phenolic compounds from Citrus aurantium L. with anti-colorectal cancer cells activity by UHPLC-Q-TOF/MS.

Natural plants are rich sources of various bioactive compounds. Consequently, the efficiently isolation of these bioactive components has always attracted considerable attention. Our work aims to demonstrate a framework for bioactivity guided isolation of potential effective compounds from the complex food materials. We demonstrated its application for isolation of phenolic compounds with anti-proliferative activity against colorectal cancer cells (CRCs) from Citrus aurantium L. Firstly, phenolic rich fraction was successfully identified as the main effective components that could simultaneously suppress the growth of CRCs and inhibit Wnt signaling. In order to obtain the bioactive phenolic constituents, a detailed study was performed by optimizing the purification conditions. Two phenolic rich fractions (40% and 60% ethanol elution fractions) were then obtained by AB-8 macroporous resins under optimized condition. Finally, the main components (65 compounds) were tentatively identified from the 40% ethanol eluant by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) analysis. Notably, there were five of the phytochemicals (Feruloylagmatine, Haploside C, Sagittatin A, Linderagalactone C and Koparin-2'-methyl ether) which were hitherto unidentified in Citrus aurantium L. fruit. In conclusion, this study showed that under the principle of bioactivity guided strategy, phenolic constituents with potential anti-CRCs activity were isolated from Citrus aurantium L.

Comparison of 3 hyperuricemia mouse models and evaluation of food-derived anti-hyperuricemia compound with spontaneous hyperuricemia mouse model.

Hyperuricemia animal models have long been used for evaluating food-derived anti-hyperuricemia compounds. Fructose and potassium oxonate are commonly used for developing hyperuricemia mouse model. Recent research also developed spontaneous hyperuricemia model by uricase knockout (Uox-/-). In this work, we evaluated 3 kinds of models with the same gene background to illustrate the differences between the treatments. Unlike the uric acid levels in potassium oxonate (224.79 ± 33.62 µmol/L) and Uox-/- groups (458.39 ± 38.29 µmol/L), fructose treatment did not lead to higher serum uric acid level (174.93 ± 30.46 µmol/L) comparing to the control group (153.53 ± 40.96 µmol/L). However, abnormal glycometabolism only developed in the fructose and the Uox-/- group. In addition, anemia, inflammasome and severe renal injury occurred in the Uox-/- group. The Uox-/- mice were then treated with puerarin and allopurinol, and found that puerarin could reduce serum uric acid and alleviated the serious renal damage associated with high uric acid. Thus, the Uox-/- mice could be a suitable model for screening and evaluating anti-hyperuricemia compounds.

Effect of oral and intraperitoneal administration of walnut-derived pentapeptide PW5 on cognitive impairments in APPSWE/PS1ΔE9 mice.

Food-derived bioactive peptides, encrypted in native protein sequence, have attracted enormous research attention due to its potential in the prevention and/or treatment of a broad range of diseases. However, administration route poses a great challenge to their development and commercial applications. Patient-friendly delivery of bioactive peptides which also enhances its efficacy urgently remain to be addressed. Here we compared the effects of oral administration (PO) to intraperitoneal injection (IP) of a walnut-derived bioactive pentapeptide PW5 (Pro-Pro-Lys-Asn-Trp) in cognitive improvement capacity in APPSWE/PS1ΔE9 transgenic mice. Strikingly, we found that only PO administration of PW5 could effectively ameliorate cognitive impairments and reduce the ß-amyloid deposits in the brain compared to the IP administration. This may be attributable to alterations in the gut microbiota communities, including alterations in microbial α- and ß-diversities after PO treatment, leading to the reversal of the relative abundances of ten differential genera (e.g. Acinetobacter, Lactobacillus, Akkermansia, Allobaculum, Adlercreutzia, Coriobacteriaceae, unclassified_p_ Firmicutes, Desulfovibrionaceae, Oscillospira and Anaeroplasma) which are highly correlated with disease progression. Thus, this study has leveraged on PW5 to proof the superior efficacy of oral delivery to injection delivery in improving cognitive impairments in vivo, suggesting that oral delivery might be highly recommended as a prioritized delivery route in the development of food-derived peptides.

Culture and establishment of self-renewing human liver 3D organoids with high uric acid for screening antihyperuricemic functional compounds.

Hyperuricemia (HUA) is a metabolic disease caused by disorders of purine metabolism, the prevalence of which has increased worldwide. At present, most drugs aimed at lowering uric acid have toxic side effects, and in vitro screening of uric acid-lowering active substances are inefficient. Here, a long-term 3D human liver organoid culture system with high uric acid for screening and evaluating the efficacy of uric acid-lowering functional compounds. This liver organoids can be established from single hepatocytes and grown for multiple months, while retaining key morphological and functional features. Furthermore, establishment of HUA organoids model was verified by antihyperuricemic drugs allopurinol, as well as reported bioactive peptides, which significantly reduced uric acid production in the liver organoids (p < 0.05). The results demonstrated that it has the potential to be used as a rapid and valid in vitro model to screen antihyperuricemic compounds that mimics in vivo cell growth patterns.

Food-derived natural compounds in the management of chronic diseases via Wnt signaling pathway.

Wnt signaling pathway is an evolutionarily conserved pathway that control embryonic development, adult tissue homeostasis, and pathological processes of organisms throughout life. However, dysregulation of the Wnt signaling is associated with the occurrence of chronic diseases. In comparison with the application of chemical drugs as traditional treatment for chronic diseases, dietary agents have unique advantages, such as less side effects, multiple targets, convenience in accessibility and higher acceptability in long-term intervention. In this review, we summarized current progress in manipulating the Wnt signaling using food components and its benefits in managing chronic diseases. The underlying mechanisms of bioactive food components in the management of the disease progression via the Wnt signaling was illustrated. Then, the review focused on the function of dietary pattern (which might act via combination of foods with multiple nutrients or food ingredients) on targeting Wnt signaling at multiple level. The potential caveats and challenges in developing new strategy via modulating Wnt-associated diseases with food-based agents and appropriate dietary pattern are also discussed in detail. This review shed light on the understanding of the regulatory effect of food bioactive components on chronic diseases management through the Wnt signaling, which can be expanded to other specific signaling pathway associated with disease.

Haematococcus Pluvialis Extends Yeast Lifespan and Improves Slc25a46 Gene Knockout-Associated Mice Phenotypic Defects.

SCOPE: Aging has become one of major concern worldwide. It is therefore of great significance in finding food resources as therapeutic candidates for aging-related functional decline improvement and prevention. This study aimed to define the potency of Haematococcus pluvialis (H. pluvialis) as an anti-aging food resource. METHODS AND RESULTS: Yeast is used to explore the anti-aging effects of H. pluvialis. The result showed that H. pluvialis extract could effectively extend yeast chronological lifespan (CLS) by reducing intracellular reactive oxygen species (ROS) levels, promoting mitochondrial membrane potential (MMP) levels and accumulating storage carbohydrate (glycogen). Subsequently, Slc25a46 knockout (Slc25a46-/- ) mice with mitochondrial dysfunction are fed with 100 mg kg-1 H. pluvialis extracts for 10 days. The in vivo data demonstrated that H. pluvialis extract could effectively improve the phenotypic deficits, including underweight, muscle weakness, redox imbalance, and mitochondrial respiratory chain dysfunction, etc., in Slc25a46-/- mice. CONCLUSIONS: This work highlights that the mitochondria may be a potential therapeutic target for combating aging, and demonstrated that H. pluvialis, as a dietary supplement, may potentially be an effective preventive substance that may contribute to the promotion of healthy aging.

Codonopsis pilosula polysaccharide in synergy with dacarbazine inhibits mouse melanoma by repolarizing M2-like tumor-associated macrophages into M1-like tumor-associated macrophages.

BACKGROUND: The incidence and associated mortality of melanoma have increased significantly in recent years but treatment options are plagued with many undesirable side effects. Traditional Chinese herbal medicine polysaccharides are gaining increasing attention due to their potential role in the treatment of chronic diseases including tumors and the regulation of the immune system. METHODS: In this study, the potential effects of Ganoderma lucidum crude polysaccharides (GLCP) and Codonopsis pilosula crude polysaccharides (CPCP) on melanoma in C57 mice were explored. In addition, the inhibition and repolarization effect of digested Codonopsis pilosula polysaccharide (dCPP) on the proliferation of tumor-associated macrophages (TAMs) with M2-like phenotype induced by IL-4 were investigated. RESULTS: The results showed that the various polysaccharides could significantly reduce tumor volume in melanoma mice. GLCP and GLCP + CPCP could further significantly reduce the number of CD68+ macrophages in tumors and also prolong survival in melanoma mice to a certain extent. Significantly, dCPP could inhibit the proliferation of IL-4-induced M2-like TAMs, and significantly increase the mRNA expression levels of IL-1, IL-6, iNOS and TNF-a, thereby promoting the repolarization of M2-like TAMs to M1-like TAMs. CONCLUSION: Overall, it could be deduced that GLCP, CPCP and dCPP hold great potential as safe therapeutic options for melanoma and an immune-modulator which may require further exploration.

The associations of gut microbiota and fecal short-chain fatty acids with bone mass were largely mediated by weight status: a cross-sectional study.

PURPOSE: We aimed to investigate whether the gut microbiota and fecal short-chain fatty acids (SCFAs) are associated with bone mass in healthy children aged 6-9 years. METHODS: In this study, 236 healthy children including 145 boys and 91 girls were enrolled. 16S rRNA gene sequencing was used to characterize the composition of their gut microbiota. Total and 10 subtypes of SCFAs in the fecal samples were determined by high-performance liquid chromatography. Dual X-ray absorptiometry was used to measure the bone mineral density (BMD) and bone mineral content (BMC) for total body (TB) and total body less head (TBLH). Z score of TBLH BMD was calculated based on the recommended reference. RESULTS: Four gut microbiota principal components (PCs) were identified by the compositional principal component analysis at the genus level. After adjustment of covariates and controlling for the false discovery rate, multiple linear regression analysis showed that PC3 score (positive loadings on genera Lachnoclostridium and Blautia) was significantly negatively associated with TBLH BMD/BMC/Z score, TB BMC and pelvic BMD (ß: - 0.207 to - 0.108, p: 0.002-0.048), whereas fecal total and several subtypes of SCFAs were correlated positively with TBLH BMD/Z score and pelvic BMD (ß: 0.118-0.174, p: 0.038-0.048). However, these associations disappeared after additional adjustment for body weight. Mediation analysis suggested that body weight significantly mediated 60.4% and 78.0% of the estimated association of PC3 score and SCFAs with TBLH BMD Z score, respectively. CONCLUSIONS: The associations of gut microbiota composition and fecal SCFA concentrations with bone mass in children were largely mediated by body weight.

Exploring the microbiota-Alzheimer's disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation.

Gut microbiota is proven to be involved in the development of beta amyloid (Aß) pathology in Alzheimer's disease (AD). Since there are difficulties in translating microbiota findings based on germ-free mice into clinical practice, here, we used short-term antibiotic cocktail treatment to develop a novel model with a near-germ-free status and without impacting Aß pathology. Three months old APPSWE/PS1ΔE9 mice were fed with antibiotic cocktails for two weeks by gavage to obtain a near "germ-free" status, and then received the donor fecal matter from the 16 months old APPSWE/PS1ΔE9 mice for 7 consecutive days. Fecal pellets were collected prior to antibiotics treatment, following antibiotic exposure, prior to and following fecal microbiota transplantation for gut microbiota analysis. Also, Aß pathology, astrocyte and microglia morphology were further explored. Pre-antibiotic-treated mice successfully allowed engraftment of gut microbiota following 7 consecutive days gavage with aged APPSWE/PS1ΔE9 mice microbiota. Microbiota reconstitution by transplantation was largely attributable to the donor source (e.g. g_Coriobacteriaceae and g_Clostridium) and led to a significant increase in Aß plaques. Surprisingly, astrocyte activation around Aß plaques was suppressed rather than microglia, the well-recognized plaque phagocytic cell type in Aß clearance, following microbiota engraftment. Our findings provide a novel framework for understanding the mechanisms of AD through the gut-brain axis and the translation of gut microbiota manipulation from bench to clinical practice.

Bifidobacterium Lactis Probio-M8 regulates gut microbiota to alleviate Alzheimer's disease in the APP/PS1 mouse model.

PURPOSE: Studies have shown that Alzheimer's disease is associated with significant alterations in the gut microbiota. But the effect of probiotics and/or prebiotics on Alzheimer's disease still remains to be explored. The aim of this study was to determine whether Bifidobacterium Lactis Probio-M8 could alleviate Alzheimer's disease pathophysiologies in the APP/PS1 transgenic mouse model. METHODS: 4-month old APP/PS1 mice were randomly put into two groups and fed with either Probio-M8 or saline water for 45 days. Fecal samples of mice were collected at the beginning and the end of the treatment period to determine the composition of the gut microbiota via 16S ribosomal RNA sequencing technology. The number and size of Aß plaques in the brain were quantified. In addition, Y maze, novel object recognition and nest building were employed to access cognitive function in the 8-months old APP/PS1 mice at the end of the treatment period. CONCLUSION: Our results demonstrated that Probio-M8 reduced Aß plaque burden in the whole brain and protected against gut microbiota dysbiosis. Furthermore, Probio-M8 could alleviate cognitive impairment in the APP/PS1 mouse.

Identification of Microbiota within Aß Plaque in APP/PS1 Transgenic Mouse.

Microbes like viruses, bacteria, and fungi have all been reported in the brain of Alzheimer's postmortem patients and/or AD mouse model; however, the relationship between brain microbes and Aß plaque deposition remains to be elucidated. In the present study, we first analyzed bacteria populations in the brain of 4-, 5-, and 6-month-old APP/PS1 mice and then examined the Aß-positive loads of APP/PS1 mouse at 9 months old to identify bacteria in the brain by 16S rDNA sequencing. Finally, blood-brain barrier permeability was measured by injecting dextrans through the tail vein. Surprisingly, the diversity of microbial community gradually decreased in APP/PS1 mouse while wild-type mouse showed no obvious regularity. Moreover, Aß-positive deposits in the brain showed a significantly higher relative abundance of microbiota than Aß-negative tissues and age-matched wild-type mouse brain tissues. In addition, an increase in blood-brain barrier permeability was also observed in APP/PS1 mouse. The present study revealed the exact location of microbes within the Aß plaques in the brain and suggested the potential antimicrobial effect of the Aß peptide. We strongly recommend that future research on microbiota-related AD pathology should focus on the migration route of microbiota into the brain and how the microbiota enhance AD progression.

The associations of the gut microbiome composition and short-chain fatty acid concentrations with body fat distribution in children.

BACKGROUND & AIMS: Previous studies linking the gut microbiome with childhood obesity largely used the body mass index to measure obesity and reached inconsistent findings. Little evidence has linked the gut microbiome to regional body fat deposition. We investigated whether the abundance of specific taxa in the gut microbiota and the concentrations of short-chain fatty acids (SCFAs) were associated with the content and regional deposition of body fat in children. METHODS: This cross-sectional study involved 236 children aged 6-9 years. The fat mass contents/percentages in the total body and the android, gynoid, and limb regions were determined by dual-energy X-ray absorptiometry, and the android-to-gynoid fat mass ratio and fat-to-lean mass ratios were calculated. Fecal samples were subjected to16S rRNA amplicon sequencing, and the fecal SCFA concentrations were quantified via high-performance liquid chromatography. RESULTS: A weighted gene co-expression network analysis identified seven modules of co-expressed operational taxonomic units (OTUs). A total of 57 OTUs from 4 key modules were selected for further analysis. After adjustment of covariates and controlling for the false discovery rate (FDR), a multiple linear regression analysis revealed significant correlations of the abundances of some OTUs with obesity and body fat measures. For instance, the OTUs classified to the species Ruminococcus gnavus and Flavonifractor plautii showed significant negative correlations with the total and regional body fat (ß: -0.250 to -0.180, PFDR: 0.041-0.049), whereas OTUs belonging to the genera Blautia and Romboutsia exhibited positive correlations with body fat measures (ß: 0.184-0.222, PFDR: 0.041-0.049). The fecal concentrations of acetic, propionic, and butyric acids and total SCFAs were significantly positively correlated with various parameters of body fat distribution (ß: 0.160-0.275, PFDR: <0.001-0.042). CONCLUSION: The gut microbiome and SCFAs are significantly associated with obesity and body fat distribution in pediatric population.