The impact of sarcopenia on the incidence of postoperative outcomes following spine surgery: Systematic review and meta-analysis.

PURPOSE: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015). CONCLUSION: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.

Serine synthesis controls mitochondrial biogenesis in macrophages.

Mitochondrial dysfunction is the pivotal driving factor of multiple inflammatory diseases, and targeting mitochondrial biogenesis represents an efficacious approach to ameliorate such dysfunction in inflammatory diseases. Here, we demonstrated that phosphoglycerate dehydrogenase (PHGDH) deficiency promotes mitochondrial biogenesis in inflammatory macrophages. Mechanistically, PHGDH deficiency boosts mitochondrial reactive oxygen species (mtROS) by suppressing cytoplasmic glutathione synthesis. mtROS provokes hypoxia-inducible factor-1α signaling to direct nuclear specificity protein 1 and nuclear respiratory factor 1 transcription. Moreover, myeloid Phgdh deficiency reverses diet-induced obesity. Collectively, this study reveals that a mechanism involving de novo serine synthesis orchestrates mitochondrial biogenesis via mitochondrial-to-nuclear communication, and provides a potential therapeutic target for tackling inflammatory diseases and mitochondria-mediated diseases.

Targeting methionine metabolism in cancer: opportunities and challenges.

Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development that target tumor methionine metabolism. We also delineate the challenges of methionine blockade therapies in cancer and discuss emerging strategies to address them.

Serine synthesis sustains macrophage IL-1ß production via NAD+-dependent protein acetylation.

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1ß production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1ß expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1ß maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1ß production, providing a potential inflammatory disease target.

A novel antibacterial strategy for targeting the bacterial methionine biosynthesis pathway.

Bacterial pathogens reprogramme their metabolic networks to support growth and establish infection at specific sites. Bacterial central metabolism has been considered attractive for developing antimicrobial drugs; however, most metabolic enzymes are conserved between humans and bacteria. This study found that blockade of methionine biosynthesis in Citrobacter rodentium and Salmonella enteritidis inhibited bacterial growth and activity of the type III secretion system, resulting in severe defects in colonization and pathogenicity. In addition, α-methyl-methionine was found to inhibit the activity of methionine biosynthetic enzyme MetA, and consequently reduce the virulence and pathogenicity of enteric pathogens. These findings highlight the crucial role of methionine in bacterial virulence, and describe a potential new drug target.

Flexible Wearable Electronic Fabrics with Dual Functions of Efficient EMI Shielding and Electric Heating for Triboelectric Nanogenerators.

Traditional conductive fabrics are prepared by the synthesis of conductive polymers and the coating modification of metals or carbon black conductive materials. However, the conductive fabrics cause a significant decline in performance after washing or mechanical wear, which limits their application. Moreover, the single function of the traditional conductive fabric is also the reason that limits its wide application. In order to prepare a wearable, stable, high-performance, washable, multifunctional conductive fabric, we have carried out related research. In this work, polydopamine was used as a bonding layer, an adsorption reduction layer, and a protective layer to improve the bonding between silver nanoparticles and carbon nanotubes (CNTs) on the polyester fabric surface so as to prepare a multifunctional conductive fabric with a high-stability "sandwich" structure, in which a Ag-NPS@CNT structure acting as an intermediate conductive layer formed on the inner layer PDA@CNT by electroless silver plating and the outermost layer PDA@CNT coated on the surface of the intermediate conductive layer by the impregnation-drying method. The sheet resistance of an E-Fabric can reach 2.11 Ω/□ due to the uniform and dense conductive path formed by the special structure Ag-NPs@CNT. At a low voltage of 1.5 V, the E-Fabric can reach 117 °C in 50 s and remain stable. The electrical conductivity and current heating properties of the E-Fabric remain good even after multiple washing or bending tests. Due to its stable and outstanding electrical conductivity, the E-Fabric has an electromagnetic shielding efficiency (SET) of 35.3 dB in the X-band (8.2-12.4 GHz). In addition, E-Fabric-based spin-coated poly(methyl methacrylate) or polydimethylsiloxane electrodes exhibit excellent performance in nanogenerators. Through the low-frequency friction of the human body, transient voltages up to 4 V can be generated from a 2 cm × 2 cm electrode sample. The output power of a single generator can reach about 12 nW/cm2. Therefore, an E-Fabric is considered to have great potential in the fields of electric heating, electromagnetic shielding, and smart wearable devices.

The vertical transmission of Salmonella Enteritidis in a One-Health context.

Salmonella enterica serovar Enteritidis (S. Enteritidis, SE) is a foodborne zoonotic pathogen, causing economic losses in animal husbandry and large numbers of human deaths and critically threatening economic development and public health. Human infection with SE has complex transmission routes, involving the environment, animal reservoirs, and water in a One-Health context. Food-producing animals, particularly poultry and livestock, are regarded as the most common sources of SE infection in humans. However, there is little known about the vertical transmission of SE in a One-Health context. In this review, we analyze the ecological significance of SE in a One-Health context. Importantly, we focus on the difference in vertical transmission of SE in poultry, livestock, and humans. We introduce the transmission pathway, describe the immune mechanisms, and discuss the models that could be used for studying the vertical transmission of SE and the strategy that prevention and control for vertical transmission of SE into the future from a One-Health perspective. Together, considering the vertical transmission of SE, it is helpful to provide important insights into the control and decontamination pathways of SE in animal husbandry and enhance knowledge about the prevention of fetal infection in human pregnancy.

Regulatory Mechanisms between Quorum Sensing and Virulence in Salmonella.

Salmonella is a foodborne pathogen that causes enterogastritis among humans, livestock and poultry, and it not only causes huge economic losses for the feed industry but also endangers public health around the world. However, the prevention and treatment of Salmonella infection has remained poorly developed because of its antibiotic resistance. Bacterial quorum sensing (QS) system is an intercellular cell-cell communication mechanism involving multiple cellular processes, especially bacterial virulence, such as biofilm formation, motility, adherence, and invasion. Therefore, blocking the QS system may be a new strategy for Salmonella infection independent of antibiotic treatment. Here, we have reviewed the central role of the QS system in virulence regulation of Salmonella and summarized the most recent advances about quorum quenching (QQ) in virulence attenuation during Salmonella infection. Unraveling the complex relationship between QS and bacterial virulence may provide new insight into the therapy of pathogen infection.

GABA signaling enforces intestinal germinal center B cell differentiation.

Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA+ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.

Influence of Experimental Skull Defects on Brain.

ABSTRACT: This study was aimed to observe the effects of skull defects on the brain in rats and further to investigate its underlying pathophysiological. Three different sizes of skull were removed in rats to produce models of skull defect, and then the behavioral changes were detected using a grip strength meter and neurobehavioral severity scale scores. The authors further examined the levels of cell apoptosis and autophagy, the cerebral blood flow with immunoblotting, and immunofluorescence micro-ultrasound system, respectively. The authors found that the sensory function but not the grip was impaired on the 6th day after a 5 × 10 mm defect while the motor function was on the 2nd day. In addition, the authors found an increment in B-cell lymphoma-2/BCL2-Associated X (Bcl2/Bax) and LC3 II/I expression, a maker of apoptosis and autophagy, respectively, in the defective hemisphere especially at the edge of the defective area. Importantly, the blood flow of internal carotid artery began to decline at 2 hours, and reached minimum on the 4th day, but began to recover on the 6th day in the hemi-defect group. In conclusion, a larger skull defect could impair the cognitive function but not the motor function and its underlying pathophysiology were mainly related to a decrease in cerebral flow.

The Amino Acid-mTORC1 Pathway Mediates APEC TW-XM-Induced Inflammation in bEnd.3 Cells.

The blood-brain barrier (BBB) is key to establishing and maintaining homeostasis in the central nervous system (CNS); meningitis bacterial infection can disrupt the integrity of BBB by inducing an inflammatory response. The changes in the cerebral uptake of amino acids may contribute to inflammatory response during infection and were accompanied by high expression of amino acid transporters leading to increased amino acid uptake. However, it is unclear whether amino acid uptake is changed and how to affect inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells in response to Avian Pathogenic Escherichia coli TW-XM (APEC XM) infection. Here, we firstly found that APEC XM infection could induce serine (Ser) and glutamate (Glu) transport from extracellular into intracellular in bEnd.3 cells. Meanwhile, we also shown that the expression sodium-dependent neutral amino acid transporter 2 (SNAT2) for Ser and excitatory amino acid transporter 4 (EAAT4) for Glu was also significantly elevated during infection. Then, in amino acid deficiency or supplementation medium, we found that Ser or Glu transport were involving in increasing SNAT2 or EAAT4 expression, mTORC1 (mechanistic target of rapamycin complex 1) activation and inflammation, respectively. Of note, Ser or Glu transport were inhibited after SNAT2 silencing or EAAT4 silencing, resulting in inhibition of mTORC1 pathway activation, and inflammation compared with the APEC XM infection group. Moreover, pEGFP-SNAT2 overexpression and pEGFP-EAAT4 overexpression in bEnd.3 cells all could promote amino acid uptake, activation of the mTORC1 pathway and inflammation during infection. We further found mTORC1 silencing could inhibit inflammation, the expression of SNAT2 and EAAT4, and amino acid uptake. Taken together, our results demonstrated that APEC TW-XM infection can induce Ser or Glu uptake depending on amino acid transporters transportation, and then activate amino acid-mTORC1 pathway to induce inflammation in bEnd.3 cells.

Inclusive growth and environmental sustainability: the role of institutional quality in sub-Saharan Africa.

Growth and environment literature has gained much attention in recent times. However, the emphasis was laid on the conventional economic growth or gross domestic product at the expense of the category of growth that is evenly shared and whose social benefits are far reaching than just an increase in the overall economic pie. It is on this note that the present paper looks at the type of relationship between growth and environment with particular emphasis on growth that is all inclusive. Data are sourced from World Governance and Development Indicators (WGI and WDI) and an index of inclusive growth constructed using principal component analysis (PCA). The findings indicate that institutional quality plays a major role in enhancing growth-environmental sustainability. The results further find a new phenomenon called environmental inclusive-growth Kuznets curve (EIKC) and added to the EKC debate. That is, at the early phase of inclusive growth, environmental degradation rises as well but environmental quality improves with the rise in inclusive growth at a higher phase of the relationship. The study recommends that policymakers should encourage the economies of sub-Saharan Africa to pursue inclusive growth and not compromise it for sustainability since sustainability comes later. Institutional quality which serves as a transmission mechanism in the study can as well be used as a robust and efficient structure to avoid adverse environmental externalities of inclusive growth.

Minimally invasive surgery for hilar cholangiocarcinoma: a multicenter retrospective analysis of 158 patients.

BACKGROUND: Curative resection of hilar cholangiocarcinoma (HC) is typically carried out using open surgery. In the present study, we examined the safety (postoperative complication) and effectiveness (resection margin status and patient survival) of minimally invasive surgery (MIS) for HC. METHODS: This retrospective analysis included 158 patients receiving MIS for HC at 10 participating centers between December 2013 and November 2019. Patient demographics, surgical outcomes, and oncological outcomes were retrospectively analyzed. RESULTS: Clinical information obtained from 10 different clinical centers did not show any evident cohort-bias clustering. One hundred and twenty-six (79.7%) patients underwent LRHC, 12 (7.6%) patients underwent RARHC, conversion to an open procedure occurred in 20 (12.7%) patients. The operation time and estimated blood loss were 410.8 ± 128.9 min and 477.8 ± 706.3 mL, respectively. The surgical radicality of the 158 patients was R0, 129 (81.6%); R1, 20 (18.4%) and R2, 9 (5.7%). Grades I-II complications was occurred in 68 (43.0%) patients. Severe morbidity (grade III-V) occurred in 14 (8.7%) patients. The median overall survival in whole cohort was 25.4 months. The overall survival rate was 67.6% at year 1, 28.8% at year 3, and 19.2% at year 5. Comparing the first half of MISHC performed by each center with the following cases, the operation time and postoperative hospital stay does not decrease with the increasing cases. On literature review, MISHC is non-inferior to open surgery at least in perioperative period. CONCLUSIONS: In this Chinese MIS for HC multicenter study, the largest to date, long-term overall survival rates after MIS appear comparable to those reported in current open series. Further randomized controlled trials are necessary to assess the global impact of MISHC.

Impacts of Amino Acids on the Intestinal Defensive System.

The intestine interacts with a diverse community of antigens and bacteria. To keep its homeostasis, the gut has evolved with a complex defense system, including intestinal microbiota, epithelial layer and lamina propria. Various factors (e.g., nutrients) affect the intestinal defensive system and progression of intestinal diseases. This review highlights the current understanding about the role of amino acids (AAs) in protecting the intestine from harm. Amino acids (e.g., arginine, glutamine and tryptophan) are essential for the function of intestinal microbiota, epithelial cells, tight junction, goblet cells, Paneth cells and immune cells (e.g., macrophages, B cells and T cells). Through the modulation of the intestinal defensive system, AAs maintain the integrity and function of the intestinal mucosa and inhibit the progression of various intestinal diseases (e.g., intestinal infection and intestinal colitis). Thus, adequate intake of functional AAs is crucial for intestinal and whole-body health in humans and other animals.

Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from the homeostasis imbalance of intestinal microenvironment, immune dysfunction, environmental and genetic factors, and so on. This disease is associated with multiple immune cells including regulatory T cells (Tregs). Tregs are a subset of T cells regulating the function of various immune cells to induce immune tolerance and maintain intestinal immune homeostasis. Tregs are correlated with the initiation and progression of IBD; therefore, strategies that affect the differentiation and function of Tregs may be promising for the prevention of IBD-associated pathology. It is worth noting that tryptophan (Trp) metabolism is effective in inducing the differentiation of Tregs through microbiota-mediated degradation and kynurenine pathway (KP), which is important for maintaining the function of Tregs. Interestingly, patients with IBD show Trp metabolism disorder in the pathological process, including changes in the concentrations of Trp and its metabolites and alteration in the activities of related catalytic enzymes. Thus, manipulation of Treg differentiation through Trp metabolism may provide a potential target for prevention of IBD. The purpose of this review is to highlight the relationship between Trp metabolism and Treg differentiation and the role of this interaction in the pathogenesis of IBD.

Effects of GABA Supplementation on Intestinal SIgA Secretion and Gut Microbiota in the Healthy and ETEC-Infected Weanling Piglets.

Pathogenic enterotoxigenic Escherichia coli (ETEC) has been considered a major cause of diarrhea which is a serious public health problem in humans and animals. This study was aimed at examining the effect of γ-aminobutyric acid (GABA) supplementation on intestinal secretory immunoglobulin A (SIgA) secretion and gut microbiota profile in healthy and ETEC-infected weaning piglets. A total of thirty-seven weaning piglets were randomly distributed into two groups fed with the basal diet or supplemented with 40 mg·kg-1 of GABA for three weeks, and some piglets were infected with ETEC at the last week. According to whether ETEC was inoculated or not, the experiment was divided into two stages (referred as CON1 and CON2 and GABA1 and GABA2). The growth performance, organ indices, amino acid levels, and biochemical parameters of serum, intestinal SIgA concentration, gut microbiota composition, and intestinal metabolites were analyzed at the end of each stage. We found that, in both the normal and ETEC-infected piglets, jejunal SIgA secretion and expression of some cytokines, such as IL-4, IL-13, and IL-17, were increased by GABA supplementation. Meanwhile, we observed that some low-abundance microbes, like Enterococcus and Bacteroidetes, were markedly increased in GABA-supplemented groups. KEGG enrichment analysis revealed that the nitrogen metabolism, sphingolipid signaling pathway, sphingolipid metabolism, and microbial metabolism in diverse environments were enriched in the GABA1 group. Further analysis revealed that alterations in microbial metabolism were closely correlated to changes in the abundances of Enterococcus and Bacteroidetes. In conclusion, GABA supplementation can enhance intestinal mucosal immunity by promoting jejunal SIgA secretion, which might be related with the T-cell-dependent pathway and altered gut microbiota structure and metabolism.

Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet.

Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice.IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

Perspective: Methionine Restriction-Induced Longevity-A Possible Role for Inhibiting the Synthesis of Bacterial Quorum Sensing Molecules.

Methionine restriction (MR) extends lifespans in multiple species through mechanisms that include enhanced oxidative stress resistance and inhibition of insulin/insulin-like growth factor I (IGF-I) signaling. Methionine and S-adenosylmethionine (SAM) are the essential precursors of bacterial quorum sensing (QS) molecules, and therefore, MR might also affect bacterial communication to prevent enteric bacterial infection as well as chronic inflammation, which contributes to lifespan prolongation. Here, we discuss the influence of MR on oxidative stress resistance and inhibition of insulin/IGF-I cell signaling and further propose a potential mechanism involving bacterial QS inhibition for lifespan extension. Unraveling the connection between MR and inhibition of QS provides new strategies for combating infectious diseases, resulting in enriched understanding of MR-induced lifespan extension.

Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring's intestinal microbiota and plasma metabolites.

Maternal nutrition during late pregnancy and lactation is highly involved with the offspring's health status. The study was carried out to evaluate the effects of different ratios of methionine and cysteine (Met/Cys: 46% Met, 51% Met, 56% Met, and 62% Met; maintained with 0.78% of total sulfur-containing amino acids; details in "Materials and methods") supplements in the sows' diet from late pregnancy to lactation on offspring's plasma metabolomics and intestinal microbiota. The results revealed that the level of serum albumin, calcium, iron, and magnesium was increased in the 51% Met group compared with the 46% Met, 56% Met, and 62% Met groups. Plasma metabolomics results indicated that the higher ratios of methionine and cysteine (0.51% Met, 0.56% Met, and 0.62% Met)-supplemented groups enriched the level of hippuric acid, retinoic acid, riboflavin, and δ-tocopherol than in the 46% Met group. Furthermore, the 51% Met-supplemented group had a higher relative abundance of Firmicutes compared with the other three groups (P < 0.05), while the 62% Met-supplemented group increased the abundance of Proteobacteria compared with the other three groups (P < 0.05) in piglets' intestine. These results indicated that a diet consisting with 51% Met is the optimum Met/Cys ratio from late pregnancy to lactation can maintain the offspring's health by improving the serum biochemical indicators and altering the plasma metabolomics profile and intestinal gut microbiota composition, but higher proportion of Met/Cys may increase the possible risk to offspring's health.

Effects of dietary gamma-aminobutyric acid supplementation on the intestinal functions in weaning piglets.

This study aims to investigate the effects of dietary gamma-aminobutyric acid (GABA) supplementation on the growth performance, intestinal immunity, intestinal GABAergic system, amino acid profiles and gut microflora of the weaned piglets. Totally sixteen healthy piglets were randomly assigned into two groups to be fed with the basal diet (Con group) or the basal diet with GABA (20 mg kg-1) supplementation. Body weights and feed intakes were monitored weekly. Piglets were sacrificed after 3 weeks of GABA supplementation to collect the blood, ileum, ileal mucosa and luminal content. Immune-associated factors, GABAergic system, amino acid profiles, and microbiota in the ileum and serum amino acid profiles were explored. The results showed that GABA supplementation improved the growth performance and modulated the intestinal immunity with inhibiting the gene expressions of IL-22, proinflammatory cytokines (IL-1 and IL-18), and Muc1, but promoted the expressions of anti-inflammatory cytokines (IFN-γ, IL-4, and IL-10), TLR6 and MyD88. GABA regulated a few components of the intestinal GABAergic system, increased the levels of most amino acids in the ileal mucosa but reduced the serum amino acid profiles. GABA regulated the population and diversity of intestinal microbiota, such as the abundances of the dominant microbial populations, the community richness, and diversity of the ileal microbiota. In conclusion, GABA supplementation modulated the intestinal functions, including intestinal immunity, intestinal amino acid profiles and gut microbiota, and the results can be helpful for understanding the functions of GABA in the intestine.