Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

Driver-response relationships in a large shallow lake since the Anthropocene: Short-term abrupt perturbations versus long-term sustainable.

Lakes, as integral social-ecological systems, are hotspots for exploring climatic and anthropogenic impacts, with crucial pathways revealed by continuous sediment records. However, the response of multi-proxies in large shallow lakes to typical abrupt events and sustained drivers since the Anthropocene remains unclear. Here, we explored the driver-identification relationships between multi-proxy peaks and natural and anthropogenic events as well as the attribution of short-term perturbations and long-term pressures. To this end, sediment core records, socio-ecological data, and documented events from official records were integrated into a large shallow lake (Dongting Lake, China). Significant causal cascades and path effects (goodness-of-fit: 0.488; total effect: -1.10; p < .001) were observed among catchment environmental proxies, lake biogenic proxies, and mixed-source proxies. The peak-event identification rate (PEIR) and event-peak driving rate were proposed, and values of 28.57%-46.43% and 50%-81.25% were obtained, respectively. The incomplete accuracy of depicting event perturbations using sediment proxies was caused by various information filters both inside and outside the lake. PEIRs for compound events were 1.41 (±0.72) and 1.09 (±0.46) times greater than those for anthropogenic-dominated and natural-dominated events, respectively. Furthermore, socio-economic activity, hydrologic dynamics, land-use changes, and agriculture exerted significant and persistent pressures, cumulatively contributing 55.3%-80.9% to alterations in sediment proxies. Relatively synergistic or antagonistic trends in temporal contributions of these forces were observed after 2000, which were primarily attributed to the "Grain for Green" project and the Three Gorges Dam. This study represents one of the few investigations to distinguish the driver-response relationship of multiple proxies in large shallow lakes under typical event perturbations and long-term sustained pressures since the Anthropocene. The findings will help policymakers and managers address ecological perturbations triggered by climate change and human activities over long-term periods.

Coupled effects of human activities and river-Lake interactions evolution alter sources and fate of sedimentary organic carbon in a typical river-Lake system.

Interconnected river-lake systems record sedimentary organic carbon (OCsed) dynamics and watershed environmental changes, providing valuable information for global carbon budgets and watershed management. However, owing to the evolving river-lake interactions under global change, monitoring OCsed is difficult, thereby impeding the understanding of OCsed transport and fate. This study provided new insights into the dynamical mechanisms of OCsed in a typical river-lake system consisting of Dongting Lake and its seven inlet/outlet rivers (the three inlets of the Yangtze River and four tributaries) over the last century using stable isotope tracing and quantified the influences of climate change and human activities on OCsed. Results indicated that exogenous OC dominated the OCsed in the lake (58.2 %-89.0 %) and was lower in the west than in the east due to the differences in the material inputs and depositional conditions within the lake. Temporally, the distribution patterns of OCsed sources mainly responded to human activities in the basin rather than to climate change. Before 2005, the Yangtze River contributed the most OCsed (53.5 %-74.6 %), attributed to the high-intensity land use changes (path coefficient (r∂): 0.48, p-value < 0.01) and agriculture-industry activities (r∂: 0.44, p-value < 0.001) in the Yangtze River basin that increased soil erosion. After 2005, a large amount of Yangtze River OC was intercepted by the Three Gorges Dam, altering the OC exchange in the river-lake system and shifting OCsed dominance to the four tributaries (52.2 %-63.8 %). These findings highlight the active response of OCsed to the river-lake interaction evolution and anthropogenic control, providing critical information for regulating watershed management behavior under global change.

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines.

The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P < 0.05) at baseline. CoronaVac vaccinees with high neutralising antibodies at 6 months p.v. had an increased relative abundance of Phocaeicola dorei, a lower relative abundance of Faecalibacterium prausnitzii, and a higher concentration of L-tryptophan (P < 0.05) at baseline. A higher antibody level at 6 months p.v. was also associated with a higher relative abundance of Dorea formicigenerans at 1 month p.v. among CoronaVac vaccinees (Rho = 0.62, p = 0.001, FDR = 0.123). Of the species altered following vaccination, 79.4% and 42.0% in the CoronaVac and BNT162b2 groups, respectively, recovered at 6 months. Specific to CoronaVac vaccinees, both bacteriome and virome diversity depleted following vaccination and did not recover to baseline at 6 months p.v. (FDR < 0.1). In conclusion, this study identified potential microbiota-based adjuvants that may extend the durability of immune responses to SARS-CoV-2 vaccines.

Effects of Gut Microbiome Modulation on Reducing Adverse Health Outcomes among Elderly and Diabetes Patients during the COVID-19 Pandemic: A Randomised, Double-Blind, Placebo-Controlled Trial (IMPACT Study).

Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 [2.9%] vs. 25 [12.6], p < 0.001) and three months (0 vs. 5 [3.1%], p = 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 [41.4%] vs. 22 [19.3%], p < 0.001), improved skin condition (18 [14.1%] vs. 8 [7.0%], p = 0.043), and better mood (27 [21.2%] vs. 13 [11.4%], p = 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.

Sediment organic carbon dynamics response to land use change in diverse watershed anthropogenic activities.

Sediment organic carbon (SOC) is a precious archive that synthesizes anthropogenic processes that remove geochemical fluxes from watersheds. However, the scarcity of inspection about the dynamic mechanisms of anthropogenic activities on SOC limits understanding into how key human factors drive carbon dynamics. Here, four typical basins with similar natural but significantly diverse human contexts (high-moderate-low disturbance: XJ-ZS and YJ-LS) were selected to reconstruct sedimentation rates (SR) and SOC dynamics nearly a century based on 200-cm corers. A partial least squares path model (PLS-PM) was used to establish successive (70 years) and multiple anthropogenic data (population, agriculture, land use, etc.) quantification methods for SOC. Intensified anthropogenic disturbances shifted all SR from pre-stable to post-1960s fluctuating increases (total coefficient: high: 0.63 < low: 0.47 < medium: 0.45). Although land use change was co-critical driver of SOC variations, their trend and extent differed under the dams and other disturbances (SOC mutated in high-moderate but stable in low). For high basin, land use changes increased (0.12) but dams reduced (-0.10) the downstream SOC. Furthermore, SOC mutation corresponded to soil erosion due to urbanization in both periods A and B. For moderate, SOC was reversed with the increase in afforestation and cropland (-0.19) due to the forest excitation effect and deep ploughing, which corresponded to the drought in phase B and the anthropogenic ecological project in A. For low, the increase in SOC corresponded to the Great Leap Forward deforestation in period B and the reed sweep in A, which suggested the minor land change substantially affected (0.16) SOC in fragile environments. Overall, SOC dynamics revealed that anthropogenic activities affected terrestrial and aquatic ecosystems for near the centenary, especially land use. This is constructive for agroforestry management and reservoir construction, consistent with expectations like upstream carbon sequestration and downstream carbon stabilization.

Anthropogenic activities control the source dynamics of sediment organic carbon in the lower reach of an inland river.

Sediment organic carbon (SeOC) sources with rich information can be used as a "historical archive" reflecting anthropogenic activities in the catchment, which is crucial to carbon management in the watershed. Anthropogenic activities and hydrodynamic conditions significantly influence the river environment and are reflected by the SeOC sources. However, the key drivers of the SeOC source dynamics are ambiguous, which restricts the behavior of regulating the carbon output of the basin. In this study, sediment cores from the lower reach of an inland river were selected to quantify the SeOC sources based on a centennial scale. A partial least squares path model was used to establish the relationship between anthropogenic activities and hydrological conditions with the SeOC sources. Findings showed that the exogenous advantage of SeOC composition was gradually significant (early period: 54.3%; middle period: 81%; later period: 82%) from the bottom layer to the surface layer of the sediments in the lower reach of the Xiangjiang River. Factors related to anthropogenic activities controlled the external input of SeOC (δ13C: r∂ = -0.94, P < 0.001; δ15N: r∂ = -0.66, P < 0.001). Different anthropogenic activities performed different effects. Land use change aggravated soil erosion and brought more terrestrial organic carbon to the downstream. The variation of grassland carbon input was the most obvious (from 33.6% to 18.4%). In contrast, the reservoir construction intercepted upstream sediments, which might have been the main reason for the slow growth of terrestrial organic carbon input in the downstream in the later period. This study provides a specific grafting for the SeOC records - source changes - anthropogenic activities in the lower reach of the river, which provides scientific basis for watershed carbon management.

A distal super-enhancer activates oncogenic ETS2 via recruiting MECOM in inflammatory bowel disease and colorectal cancer.

Abnormal activities of distal cis-regulatory elements (CREs) contribute to the initiation and progression of cancer. Gain of super-enhancer (SE), a highly active distal CRE, is essential for the activation of key oncogenes in various cancers. However, the mechanism of action for most tumor-specific SEs still largely remains elusive. Here, we report that a candidate oncogene ETS2 was activated by a distal SE in inflammatory bowel disease (IBD) and colorectal cancer (CRC). The SE physically interacted with the ETS2 promoter and was required for the transcription activation of ETS2. Strikingly, the ETS2-SE activity was dramatically upregulated in both IBD and CRC tissues when compared to normal colon controls and was strongly correlated with the level of ETS2 expression. The tumor-specific activation of ETS2-SE was further validated by increased enhancer RNA transcription from this region in CRC. Intriguingly, a known IBD-risk SNP resides in the ETS2-SE and the genetic variant modulated the level of ETS2 expression through affecting the binding of an oncogenic transcription factor MECOM. Silencing of MECOM induced significant downregulation of ETS2 in CRC cells, and the level of MECOM and ETS2 correlated well with each other in CRC and IBD samples. Functionally, MECOM and ETS2 were both required for maintaining the colony-formation and sphere-formation capacities of CRC cells and MECOM was crucial for promoting migration. Taken together, we uncovered a novel disease-specific SE that distantly drives oncogenic ETS2 expression in IBD and CRC and delineated a mechanistic link between non-coding genetic variation and epigenetic regulation of gene transcription.

Anthropogenic-driven chronological increase of sediment organic carbon burial in a river-lake system.

Total organic carbon (TOC) in lake sediments from upstream catchments is deposited and buried in substrate, recording historical environmental changes. However, the linkage among natural variability, anthropogenic activity, and TOC burial for has not yet been clarified. This study examined the lake sediments of five 200-cm-deep dated depositional cores in west Dongting lake, China to quantify the magnitude, allocation, and amplitude of TOC burial. 44.47-59.36% of TOC burial flux was buried at 100-200 cm, suggesting lake sediments at deep layers stored considerable carbon. TOC burial rate (BRTOC) decreased along the lake entrance to its body, which was explained by the geochemical differences. Since 1900, BRTOC presented an increasing with a 4-7 times uptrend, showing three sedimentary stages with the increased human disturbance, such as deforestation, hydroelectric facilities. Moreover, the coefficient of variation of BRTOC in the third stage was lower than that in the second stage for the implementation of watershed reforestation and reservoir construction. Our findings stressed that natural variations of lake sedimentation background induced the change of TOC burial among the depositional sites, and enhanced that anthropogenic perturbation drove its chronological increases. This research unveiled the linkage between TOC burial, natural variability, and human disturbance from the perspective of burial evolutions in a lacustrine sedimentary environment.

The application and potential non-conservatism of stable isotopes in organic matter source tracing.

Organic matter (OM) tracing is critical for understanding the processes of soil redistribution and global carbon cycling. It effectively supports ecological management and global climate change prediction. Stable isotopes are generally more source-specific compared with other tracers and identify OM sources with a higher level of accuracy. Nevertheless, stable isotopes may be enriched or depleted by physical and biochemical processes such as selective migration of particles and OM mineralization in transport and sedimentary environments, making it difficult to establish links between the source and sink regions. Literature on OM source identification tends to assume a direct link between stable isotope sources and sinks, ignoring the non-conservatism of stable isotopes. There is further literature on understanding and modeling the processes that link the sources to sinks in terms of the non-conservatism of stable isotopes. The disagreement in response to the non-conservatism lies in the lack of comprehensive understanding of stable isotope fingerprinting systems and non-conservatism. The development of stable isotope fingerprinting technology is full of challenges. This review outlines the applicability of stable isotope tracers, identification mechanisms, and associated quantitative models, intending to improve the stable isotope fingerprinting system. We highlight the non-conservatism of stable isotopes in space and time caused by physical and biochemical processes. Additionally, a decision tree is established to determine the quantitative tools, evaluation indicators, and procedures related to non-conservatism. This decision tree clarifies the process from non-conservatism detection to threshold determination of statistical quantification, which can guide the end-users to better apply stable isotope to trace OM sources.

Ellagic Acid Alleviates Diquat-Induced Jejunum Oxidative Stress in C57BL/6 Mice through Activating Nrf2 Mediated Signaling Pathway.

Ellagic acid (EA) is the main constituent found in pomegranate rind, which has anti-inflammatory and antioxidant effects. However, whether EA can alleviate diquat-induced oxidative stress is still unknown. Here, the effects and mechanisms of EA on jejunum oxidative stress induced by diquat was investigated. Oxidative stress was induced in mice by administrating diquat (25 mg/kg body weight) followed by treatment with 100 mg/kg body weight EA for 5 days. Results showed that oral administration of EA significantly ameliorated diquat-induced weight loss and oxidative stress (p < 0.05) evidenced by reduced ROS production in the jejunum. Furthermore, EA up-regulated the mRNA expression of the antioxidant enzymes (Nrf2, GPX1 and HO-1) when mice were challenged with diquat, compared with the diquat group (p < 0.05). Importantly, pharmacological inhibition of Nrf2 by ML385 counteracted the EA-mediated alleviation of jejunum oxidative stress, as evidence by body weight and ROS production. Also, immunohistochemistry staining confirmed the markedly decreased jejunal Nrf2 expression. The up-regulated effect on NQO1 and HO-1 mRNA expression induced by EA was diminished in mice treated with ML385 (p < 0.05). Together, our results demonstrated that therapeutic and preventative EA treatment was effective in reducing weight loss and oxidative stress induced by diquat through the Nrf2 mediated signaling pathway.

Prophage Activation in the Intestine: Insights Into Functions and Possible Applications.

Prophage activation in intestinal environments has been frequently reported to affect host adaptability, pathogen virulence, gut bacterial community composition, and intestinal health. Prophage activation is mostly caused by various stimulators, such as diet, antibiotics, some bacterial metabolites, gastrointestinal transit, inflammatory environment, oxidative stress, and quorum sensing. Moreover, with advancements in biotechnology and the deepening cognition of prophages, prophage activation regulation therapy is currently applied to the treatment of some bacterial intestinal diseases such as Shiga toxin-producing Escherichia coli infection. This review aims to make headway on prophage induction in the intestine, in order to make a better understanding of dynamic changes of prophages, effects of prophage activation on physiological characteristics of bacteria and intestinal health, and subsequently provide guidance on prophage activation regulation therapy.

Xylo-oligosaccharide alleviates Salmonella induced inflammation by stimulating Bifidobacterium animalis and inhibiting Salmonella colonization.

Xylo-oligosaccharide (XOS), which is considered as a potential prebiotic, exhibits multiple beneficial effects on modulation of gut microbiota, strength of intestinal barrier, and inhibition of intestinal inflammation. The objective of this study is to investigate whether XOS protects against Salmonella infection by modulating gut microbiota, enhancing the intestinal barrier, and resisting colonization. C57BL/6 male mice received water supplementation with 5% XOS for 14 days before Salmonella Typhimurium infection. The results showed that XOS suppressed the Salmonella-induced inflammation, but had limited effects on tight junction molecules and mRNA expression of mucus proteins, except for claudin-1 in the colon. Data of 16S rDNA sequencing indicated that XOS modulated gut microbiota composition by significantly stimulating Bifidobacterium animalis (B. animalis), and reducing Salmonella counts. Therefore, the potential protective effects of B. animalis against Salmonella challenge were investigated as well. Bifidobacterium animalis subsp lactis BB-12 (BB12), which could markedly increase in XOS, was selected to treat mice. Similarly, Salmonella-induced inflammatory reactions were alleviated by BB12 but tight junction molecules and mucin proteins in the colonic tissues were not affected. Administration of BB12 remarkably decreased the copies of Salmonella in cecal digesta post Salmonella infection. Additionally, the decrease concentrations of cecal propionate and total short-chain fatty acids (SCFAs) in Salmonella-infected mice were reversed by BB12 treatment, and propionate performed a strong inhibitory effect on Salmonella growth in vitro. Besides that, BB12 could directly restrict Salmonella proliferation in vitro. Moreover, BB12 reduced the adhesion ability of Salmonella on the Caco-2 cells model. Our results suggest that XOS could be considered as a candidate of functional food to protect against Salmonella infection by stimulating Bifidobacterium, which then resists Salmonella colonization by maintaining the intestinal SCFAs levels and suppressing adhesibility.

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.

BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.

Early life administration of milk fat globule membrane promoted SCFA-producing bacteria colonization, intestinal barriers and growth performance of neonatal piglets.

Milk fat globule membrane (MFGM) possesses various nutritional and biological benefits for mammals, whereas its effects on neonatal gut microbiota and barrier integrity remained unclear. This study investigated the effects of MFGM administration on microbial compositions and intestinal barrier functions of neonatal piglets. Sixteen newborn piglets were randomly allocated into a CON group or MFGM group, orally administered with saline or MFGM solution (1 g/kg body weight) respectively during the first postnatal week, and all piglets were breastfed during the whole neonatal period. The present study found that the MFGM oral administration during the first postnatal week increased the plasma immunoglobulin (Ig) G level, body weight and average daily gain of piglets (P < 0.05) on 21 d. Additionally, MFGM administration enriched fecal SCFA-producing bacteria (Ruminococ aceae_UCG-002, Ruminococ aceae_UCG-010, Ruminococ aceae_UCG-004, Ruminococ aceae_UCG-014 and [Ruminococcus]_gauvrearuii_group), SCFA concentrations (acetate, propionate and butyrate; P < 0.05) and their receptor (G-protein coupled receptor 41, GPR41). Furthermore, MFGM administration promoted intestinal villus morphology (P < 0.05) and barrier functions by upregulating genes of tight junctions (E-cadherin, claudin-1, occludin and zonula occludin 1 [ZO-1]), mucins (mucin-13 and mucin-20) and interleukin (IL)-22 (P < 0.05). Positive correlation was found between the beneficial microbes and SCFA levels pairwise with the intestinal barrier genes (P < 0.05). In conclusion, orally administrating MFGM during the first postnatal week stimulated SCFA-producing bacteria colonization and SCFA generation, enhanced intestinal barrier functions and consequently improved growth performance of neonatal piglets on 21 d. Our findings will provide new insights about MFGM intervention for microbial colonization and intestinal development of neonates during their early life.

Chronological records of sediment organic carbon at an entrance of Dongting Lake: Response to historical meteorological events.

Lake sediments are the products of soil erosion and are strongly influenced by climate variability, particularly extreme meteorological events. Sediment organic carbon (SOC) can reflect environmental changes that affect sediment transport. However, the response of SOC chronological records to major meteorological events is relatively unknown. This study explored the chronological regularity of SOC and verified its variations using major historical meteorological events. Based on three sediment profiles with a depth of 230 cm at the Yuan River entrance to the West Dongting Lake (Hanshou entrance), the SOC chronology was reconstructed by employing the sedimentation rates calculated by 137Cs and 210Pb. The sedimentary environment then was interpreted via comparisons and quantitative analysis. The grain distribution and the S-shaped distribution of SOC reflected the general deposition regularity of organic carbon in lake sediments, which gradually stabilized with depth. The average sedimentation rates based on 137Cs and 210Pb were 1.310 and 1.319 cm a-1, respectively. Accordingly, SOC records covered the past 76 years via dating (0-100 cm), during which the SOC content first increased and subsequently stabilized. By comparing the data with the occurrence of 11 major historical meteorological events, we found that SOC generally increased after these events. Moreover, the frequent occurrence of meteorological events stabilized the SOC content. Severe floods had a greater impact on SOC content than severe droughts, causing SOC to change by up to 20.24% and 8.77%, respectively. Our findings suggest that major historical meteorological events can verify SOC chronological records, thereby highlighting their significant impacts on organic carbon variations in sediments.

Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages.

Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1ß, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.

Resistant Maltodextrin Alleviates Dextran Sulfate Sodium-Induced Intestinal Inflammatory Injury by Increasing Butyric Acid to Inhibit Proinflammatory Cytokine Levels.

Inflammatory bowel disease (IBD), one kind of intestinal chronic inflammatory disease, is characterized by colonic epithelial barrier injury, overproduction of proinflammatory cytokines, and fewer short-chain fatty acids (SCFAs). The present study is aimed at testing the hypothesis that resistant maltodextrin (RM), a soluble dietary fiber produced by starch debranching, alleviated dextran sulfate sodium- (DSS-) induced colitis in mice. Female C57BL/6 mice with or without oral administration of 50 mg/kg RM for 19 days were challenged with 3% DSS in drinking water to induce colitis (from day 14 to day 19). Although RM could not reverse DSS-induced weight loss or colon shortening, it reduced inflammatory cell infiltration and epithelial damage in colon tissue, as well as the transfer of intestinal permeability indicators including serum diamine oxidase (DAO) and D-lactic acid (D-LA). ELISA analysis indicated that RM significantly suppressed the increase of Th1 cytokines induced by DSS in the colon such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The levels of proinflammatory cytokines interleukin-1ß (IL-1ß), IL-17, and IL-8 in the DSS group were significantly higher than those in the control group and RM group, but no significant difference was observed in the RM-DSS group compared with the RM group. Interestingly, IL-10 levels of the DSS group were significantly higher than those of the other groups. With respect to SCFAs, DSS administration significantly decreased the concentration of faecal butyric acid while the RM-DSS group showed a tendency to increase (P = 0.08). In general, RM alleviated dextran sulfate sodium-induced intestinal inflammation through increasing the level of butyric acid and subsequently inhibiting the expression of proinflammatory cytokines.

Glucosamine Supplementation in Premating Drinking Water Improves Within-Litter Birth Weight Uniformity of Rats Partly through Modulating Hormone Metabolism and Genes Involved in Implantation.

Within-litter birth weight variation in multiparous animals has become a big issue due to high incidence of low birth weight neonates, which gives rise to high preweaning mortality and morbidity. Foetus with various birth weights is the outcome of diverse embryos competence which is affected by oocyte quality. Glucosamine (GlcN) has been reported to be involved in oocyte maturation; however, its effect on pregnant outcomes remains unknown. The present study was conducted to investigate the effects of premating GlcN supplementation via drinking water on within-litter birth weight variation and its underlying mechanism. Fifty eight Sprague-Dawley female rats were randomly assigned to one of two groups with normal drinking water or drinking water supplemented with 0.5 mM GlcN from six to eight weeks old. Variation of within-litter birth weight in the GlcN group was 5.55%, significantly lower compared with 8.17% in the control group. Birth weight was significantly increased in the GlcN group (2.27 ± 0.06) compared with the control group (2.08 ± 0.04). Both absolute and relative weights of the ovary at the end of GlcN treatment were higher in the GlcN group than in the control group (P < 0.05). In the GlcN group, there were more successfully implanted blastocysts (13.38 ± 0.63 and 15.75 ± 0.59 in the control and treatment group, respectively) with more uniform distribution along the two uterine horns compared with the control group. Besides, gene expressions of Alk3 and Bmp2 were increased in the implantation sites, while IGF-1 and Mucin-1 were decreased significantly in rats administrated with GlcN. Maternal progesterone, estradiol, and IGF-1 concentrations on D 19.5 were significantly increased, while insulin and total cholesterol levels were significantly decreased in contrast with control dams. In summary, the administration of 0.5 mM GlcN solution before mating reduced within-litter birth weight variation, accompanied with increased fetal weight. Further investigation indicated that the improved outcome of pregnancy results at least partly from the increased ovary weights of the rats, the homogeneous embryo developmental competence, the enhanced receptivity of the uterine environment, and the adjusted maternal hormone levels.

Combined supplementation of Lactobacillus fermentum and Pediococcus acidilactici promoted growth performance, alleviated inflammation, and modulated intestinal microbiota in weaned pigs.

BACKGROUND: Probiotics are important for pigs to enhance health and intestinal development, which are potential alternative to antibiotics. Many studies have reported the functions of single bacterial strain as probiotic on the animals. In this study, we evaluated effects of combined probiotics on growth performance, inflammation and intestinal microbiota in weaned pigs. One hundred and eight pigs, weaned at 28 day old (7.12 ± 0.08 kg), were randomly divided into the 3 dietary treatments with 6 pens and 6 pigs per pen (half male and half female). The experimental period lasted for 28 days and treatments were as follows: i. CONTROL: basal diet; ii. Antibiotic: the basal diet plus 75 mg· kg- 1 chlortetracycline; and iii. Probiotics: basal diet plus 4% compound probiotics. RESULTS: Supplementation probiotics improved average daily gain over the entire 28 days (P < 0.01) and feed efficiency in the last 14 days (P < 0.05) compared with the other two groups. Both probiotics and antibiotic supplementation decreased concentrations of serum pro-inflammatory cytokines interleukin-6 (P < 0.05) and interferon-γ (P < 0.01). Probiotics group had greater abundance of Lactobacillus in the caecal digesta and Firmicutes in the colonic digesta, while both probiotics and antibiotic supplementation inhibited Treponema_2 and Anaerovibrio in the caecal digesta. Caecal acetic and propionic acid (P < 0.05) of probiotics group were higher than the other two groups, whereas concentrations of colonic lactic acid and propionic acid (P < 0.05) of antibiotic group were lower than control and probiotics groups. CONCLUSIONS: These findings suggest that combined supplementation of Lactobacillus fermentum and Pediococcus acidilactici regulate the gut health and improve the host ADG and F/G by decreasing serum pro-inflammatory factors (IL-6, IFN-γ), promoting beneficial bacteria (Lactobacillus in the caecal digesta and Firmicutes in the colonic digesta), enhancing production of short chain fatty acids, and inhibiting pathogens (Treponema_2, Anaerovibrio in the caecal digesta).