Neurodegenerative diseases (NDDs) such as Alzheimer's and Parkinson's disease are increasing globally and represent a significant cause of age-related death in the population. Recent studies emphasize the strong association between environmental stressors, particularly dietary factors, and brain health and neurodegeneration unsatisfactory outcomes. Despite ongoing efforts, the efficiency of current treatments for NDDs remains wanting. Considering this, nootropic foods with neuroprotective effects are of high interest as part of a possible long-term therapeutic strategy to improve brain health and alleviate NDDs. However, since it is a new and emerging area in food and neuroscience, there is limited information on mechanisms and challenges to consider for this to be a successful intervention. Here, we seek to address these gaps by presenting a comprehensive review of possible pathways or mechanisms including mutual interactions governing nootropic food metabolism, linkages of the pathways with NDDs, intake, and neuroprotective properties of nootropic foods. We also discuss in-depth intervention with nootropic compounds and dietary patterns in NDDs, providing a detailed exploration of their mechanisms of action. Additionally, we analyze the demand, challenges, and future directions for successful development of nootropic foods targeting NDDs.

Nutrition consistently affects microbe-host interactions in the gastrointestinal tract. This study aimed to unravel how undernutrition reshapes the microbial composition and the homeostasis of epithelium in the jejunum and ileum. Sixteen late-gestation Hu-sheep were randomly assigned to the control group (n = 8, 100% ad libitum feeding levels) or the undernutrition group (n = 8, which received 30% ad libitum feeding levels). After 15-d treatment, all ewes were slaughtered, and jejunal and ileal digesta and epithelium samples were collected for 16S rRNA gene sequencing and transcriptome sequencing, respectively. Results indicated that undernutrition decreased the jejunal and ileal tissue weights (P = 0.005 and P = 0.022) and the levels of volatile fatty acids (P = 0.019 and P = 0.007) and microbial protein levels (P = 0.019 and P = 0.031) in jejunal and ileal digesta. The relative abundance of acetate producing microbiota, including Clostridia UCG-014 norank, Ruminococcus, [Ruminococcus] gauvreauii, and Lachnospiraceae _Blautia, were significantly reduced (P < 0.05) in the jejunum and ileum. Undernutrition up-regulated (P < 0.05) the expression of genes involved in amino acid synthesis and fatty acid oxidation, but down-regulated (P < 0.05) the expression of genes associated with amino acid degradation, fatty acid synthesis, and extracellular structures in jejunal and ileal epithelium. In the jejunal epithelium, genes associated with extracellular matrix-receptor interactions, cell growth, and immune response were down-regulated (P < 0.05) upon undernutrition. Taken together, undernutrition changed the microbial community in the jejunum and ileum, which altered the fermentation mode and the production of volatile fatty acids and microbial protein. These affected the energy and protein system in the epithelium and reprogrammed substance metabolism and extracellular structures, which probably further influenced cell growth and immune response. These insights provide a foundation for completely clarifying the crosstalk between small intestinal microbiota and the host.

Maintaining lipid homeostasis is important for intestinal and body health. Litchi flower essential oil (LFEO), mainly containing 9,12-Octadecadienoic acid (Z,Z)-, α-Curcumene, Gamma.-Sitosterol, α-linolenic acid, β-Bisabolene and n-Hexadecanoic acid, has been demonstrated significant anti-obesity activity. However, it remains uncertain whether LFEO could ameliorate intestinal damage associated with lipid metabolism disorders. The aim of this study was to investigate the protective effect of LFEO against intestinal injury caused by lipid disturbance in Caenorhabditis elegans. Firstly, LFEO significantly ameliorated the lipid disturbance induced by Pseudomonas aeruginosa and maintained lipid homeostasis. Secondly, LFEO maintained intestinal health by attenuating mitochondrial damage. After LFEO treatment, the intestinal width of worms was reduced by 24.82 % (on day 5) and 23.81 % (on day 7), respectively, while the intestinal breakage rate was only 15.33 %. In terms of capacity metabolism, LFEO significantly protected the neuronal structure, improved pharyngeal function, and maintained energy intake in lipid-disordered worms. The results of this study indicated that LFEO effectively reduced the intestinal damage and maintained intestinal health in lipid disorder nematodes. It made a new understanding for LFEO to reduce intestinal damage caused by lipid disorders, and provided a reference for the large-scale production of LFEO to promote the development of litchi circular economy.

Spontaneous bacterial peritonitis (SBP) is an infectious condition characterizing the presence of bacterial infection in the peritoneal fluid with no apparent source of infection within the abdomen. It is extremely rare for patients with malnutrition after colorectal cancer (CRC) surgery to develop SBP. This is the first ever case reported case of SBP resulting from intestinal barrier compromise in a patient with colorectal cancer with malnutrition.

A 72-year-old woman with malnutrition was diagnosed with CRC, and following brief nutritional support, she underwent the laparoscopic-assisted radical right hemicolectomy. The patient was then diagnosed with peritonitis after the operation. An emergency laparotomy was performed, and the patient was finally diagnosed with SBP. The patient ultimately recovered following a series of appropriate postoperative supportive treatments.

This case highlights the poor outcomes of short preoperative nutritional therapy in CRC patients with malnutrition. Further studies should investigate the role of the intestinal barrier function in the recovery of patients with CRC after surgery.

The gut barrier is the first line of defense against harmful substances and pathogens in the intestinal tract. The balance of proliferation and apoptosis of intestinal epithelial cells (IECs) is crucial for maintaining the integrity of the intestinal mucosa and its function. However, oxidative stress and inflammation can cause DNA damage and abnormal apoptosis of the IECs, leading to the disruption of the intestinal epithelial barrier. This, in turn, can directly or indirectly cause various acute and chronic intestinal diseases. In recent years, there has been a growing understanding of the vital role of dietary ingredients in gut health. Studies have shown that certain amino acids, fibers, vitamins, and polyphenols in the diet can protect IECs from excessive apoptosis caused by oxidative stress, and limit intestinal inflammation. This review aims to describe the molecular mechanism of apoptosis and its relationship with intestinal function, and to discuss the modulation of IECs' physiological function, the intestinal epithelial barrier, and gut health by various nutrients. The findings of this review may provide a theoretical basis for the use of nutritional interventions in clinical intestinal disease research and animal production, ultimately leading to improved human and animal intestinal health.

Functional loss of the motor protein myosin Vb (MYO5B) induces various defects in intestinal epithelial function and causes a congenital diarrheal disorder, namely, microvillus inclusion disease (MVID). Utilizing the MVID model mice Vil1-CreERT2;Myo5bflox/flox (MYO5BΔIEC) and Vil1-CreERT2;Myo5bflox/G519R [MYO5B(G519R)], we previously reported that functional MYO5B loss disrupts progenitor cell differentiation and enterocyte maturation that result in villus blunting and deadly malabsorption symptoms. In this study, we determined that both absence and a point mutation of MYO5B impair lipid metabolism and alter mitochondrial structure, which may underlie the progenitor cell malfunction observed in the MVID intestine. Along with a decrease in fatty acid oxidation, the lipogenesis pathway was enhanced in the MYO5BΔIEC small intestine. Consistent with these observations in vivo, RNA sequencing of enteroids generated from the two MVID mouse strains showed similar downregulation of energy metabolic enzymes, including mitochondrial oxidative phosphorylation genes. In our previous studies, we reported that lysophosphatidic acid (LPA) signaling ameliorated epithelial cell defects in MYO5BΔIEC tissues and enteroids. The present study demonstrated that the highly soluble LPA receptor (LPAR)5-preferred agonist Compound-1 improved sodium transporter localization and absorptive function and tuft cell differentiation in patient-modeled MVID animals that carry independent mutations in MYO5B. Body weight loss in male MYO5B(G519R) mice was ameliorated by Compound-1. These observations suggest that Compound-1 treatment has a trophic effect on the intestine with MYO5B functional loss through epithelial cell-autonomous pathways that can accelerate the differentiation of progenitor cells and the maturation of enterocytes. Targeting LPAR5 may represent an effective therapeutic approach for the treatment of MVID symptoms induced by different point mutations in MYO5B.NEW & NOTEWORTHY This study demonstrates the importance of MYO5B for cellular lipid metabolism and mitochondria in intestinal epithelial cells, previously unexplored functions of MYO5B. The alterations may underlie the progenitor cell malfunction observed in microvillus inclusion disease (MVID) intestines. To examine the therapeutic potential of progenitor-targeted treatments, the effects of the LPAR5-preferred agonist Compound-1 were investigated utilizing several MVID model mice and enteroids. Our observations suggest that Compound-1 may provide a therapeutic approach for treating MVID.

Depression is a common psychological disorder, accompanied by a disturbance of the gut microbiota and its metabolites. Recently, microbiota-derived tryptophan metabolism and AMPK/mTOR pathway were found to be strongly linked to the development of depression. Shugan Hewei Decoction (SHD) is a classical anti-depression traditional Chinese medicine formula. Although, we have shown that SHD exerted antidepressant effects via cecal microbiota and cecum NLRP3 inflammasome, the specific mechanism of SHD on metabolism driven by gut microbiota is unknown. In this study, we focus on the tryptophan metabolism and AMPK/mTOR pathway to elucidate the multifaceted mechanisms of SHD.

Male rats were established to the chronic unpredictable stress (CUS)/social isolation for 6 weeks, and SHD-L (7.34 g/kg/d), SHD-H (14.68 g/kg/d), Fructooligosaccharide (FOS) (3.15 g/kg/d) were given by intragastric administration once daily during the last 2 weeks. Behavioral experiments were carried out to evaluate the model. The colonic content was taken out for shotgun metagenomic sequencing combined with the untargeted metabolomics, the targeted tryptophan metabolomics. ELISA was used to detect the levels of zonula occludens 1 (ZO-1), Occludin in colon, as well as lipopolysaccharide (LPS), diamine oxidase (DAO), D-lactate (DLA) in serum. The expressions of mRNA and proteins of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway of autophagy were examined using RT-qPCR and Western blot in colon.

SHD modulated gut microbiota function and biological pathways, which were related to tryptophan metabolism. In addition, SHD could regulate microbiota-derived tryptophan production (such as reduction of 3-HK, 3-HAA etc., increment of ILA, IAA etc.), which metabolites belong to kynurenine (KYN) and indole derivatives. Further, SHD reduced intestinal permeability and enhanced the intestinal barrier function. Moreover, SHD could upregulate the levels of AMPK, microtubule associated protein light chain 3 (LC3), autophagy related protein 5 (ATG5) and Beclin1, downregulate the levels of mTOR, p62, promoted autophagy in colon. Spearman's analysis illustrated the close correlation between tryptophan metabolites and intestinal barrier, AMPK/mTOR pathway.

SHD may exert antidepressant-like effects by regulating microbiota-derived tryptophan metabolism, and triggering the AMPK/mTOR pathway of autophagy, enhancing the intestinal barrier function.

Functional loss of the motor protein, Myosin Vb (MYO5B), induces various defects in intestinal epithelial function and causes a congenital diarrheal disorder, microvillus inclusion disease (MVID). Utilizing the MVID model mice, Vil1-Cre ERT2 ;Myo5b flox/flox (MYO5BΔIEC) and Vil1-Cre ERT2 ;Myo5b flox/G519R (MYO5B(G519R)), we previously reported that functional MYO5B loss disrupts progenitor cell differentiation and enterocyte maturation that result in villus blunting and deadly malabsorption symptoms. In this study, we determined that both absence and a point mutation of MYO5B impair lipid metabolism and alter mitochondrial structure, which may underlie the progenitor cell malfunction observed in MVID intestine. Along with a decrease in fatty acid oxidation, the lipogenesis pathway was enhanced in the MYO5BΔIEC small intestine. Consistent with these observations in vivo , RNA-sequencing of enteroids generated from two MVID mouse strains showed similar downregulation of energy metabolic enzymes, including mitochondrial oxidative phosphorylation genes. In our previous studies, lysophosphatidic acid (LPA) signaling ameliorates epithelial cell defects in MYO5BΔIEC tissues and enteroids. The present study demonstrates that the highly soluble LPAR5-preferred agonist, Compound-1, improved sodium transporter localization and absorptive function, and tuft cell differentiation in patient-modeled MVID animals that carry independent mutations in MYO5B. Body weight loss in male MYO5B(G519R) mice was ameliorated by Compound-1. These observations suggest that Compound-1 treatment has a trophic effect on intestine with MYO5B functional loss through epithelial cell-autonomous pathways that may improve the differentiation of progenitor cells and the maturation of enterocytes. Targeting LPAR5 may represent an effective therapeutic approach for treatment of MVID symptoms induced by different point mutations in MYO5B.

This study demonstrates the importance of MYO5B for cellular lipid metabolism and mitochondria in intestinal epithelial cells, a previously unexplored function of MYO5B. Alterations in cellular metabolism may underlie the progenitor cell malfunction observed in microvillus inclusion disease (MVID). To examine the therapeutic potential of progenitor-targeted treatments, the effects of LPAR5-preferred agonist, Compound-1, was investigated utilizing several MVID model mice and enteroids. Our observations suggests that Compound-1 may provide a therapeutic approach for treating MVID.

Severe malnutrition is associated with infections, namely lower respiratory tract infections (LRTIs), diarrhea, and sepsis, and underlies the high risk of morbidity and mortality in children under 5 years of age. Dysregulations in neutrophil responses in the acute phase of infection are speculated to underlie these severe adverse outcomes; however, very little is known about their biology in this context. Here, in a lipopolysaccharide-challenged low-protein diet (LPD) mouse model, as a model of malnutrition, we show that protein deficiency disrupts neutrophil mitochondrial dynamics and ATP generation to obstruct the neutrophil differentiation cascade. This promotes the accumulation of atypical immature neutrophils that are incapable of optimal antimicrobial response and, in turn, exacerbate systemic pathogen spread and the permeability of the alveolocapillary membrane with the resultant lung damage. Thus, this perturbed response may contribute to higher mortality risk in malnutrition. We also offer a nutritional therapeutic strategy, nicotinamide, to boost neutrophil-mediated immunity in LPD-fed mice.

Ubiquitination is an enzymatic modification involving ubiquitin chains, that can be reversed by deubiquitination (DUB) enzymes. Ubiquitin-specific protease 7 (USP7), which is also known as herpes virus-associated ubiquitin-specific protease (HAUSP), has been shown to play a vital role in cardiovascular diseases. However, the underlying molecular mechanism by which USP7 regulates cardiomyocyte function has not been reported.

To understand the physiological function of USP7 in the heart, we constructed cardiomyocyte-specific USP7 conditional knockout mice.

We found that homozygous knockout mice died approximately three weeks after birth, while heterozygous knockout mice grew normally into adulthood. Severe cardiac dysfunction, hypertrophy, fibrosis, and cell apoptosis were observed in cardiomyocyte-specific USP7 knockout mice, and these effects were accompanied by disordered mitochondrial dynamics and cardiometabolic-related proteins.

In summary, we investigated changes in the growth status and cardiac function of cardiomyocyte-specific USP7 knockout mice, and preliminarily explored the underlying mechanism.

In this editorial, we comment on an article titled "Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases", which was published in a recent issue of the World Journal of Gastroenterology. We focused on the statement that "autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal cells". With advancing research, autophagy, and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system, has garnered extensive study. However, the significance of mitophagy, a unique selective autophagy pathway with ubiquitin-dependent and independent variants, should not be overlooked. In recent decades, mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases, especially inflammatory bowel disease, gastric cancer, and colorectal cancer. The interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms, as well as for the development of novel treatment strategies. Exploring the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been exploring. This article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation.

To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism.

Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.

HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H2O2-induced oxidative stress in NCM460 cells by up-regulating SIRT1.

HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.

Multiple sclerosis (MS) is a chronic central nervous system (CNS) disorder characterized by demyelination, neuronal damage, and oligodendrocyte depletion. Reliable biomarkers are essential for early diagnosis and disease management. Emerging research highlights the role of mitochondrial dysfunction and oxidative stress in CNS disorders, including MS, in which mitochondria are central to the degenerative process. Adenosine monophosphate-activated protein kinase (AMPK) regulates the mitochondrial energy balance and initiates responses in neurodegenerative conditions. This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aimed to comprehensively assess the literature on AMPK pathways, mitochondrial dysfunction, and in vivo studies using MS animal models. The search strategy involved the use of AMPK syntaxes, MS syntaxes, and animal model syntaxes. The PubMed, Scopus, Web of Science, and Google Scholar databases were systematically searched on August 26, 2023 without publication year restrictions. The review identified and analyzed relevant papers to provide a comprehensive overview of the current state of related research. Eight studies utilizing various interventions and methodological approaches were included. Risk of bias assessment revealed some areas of low risk but lacked explicit reporting in others. These studies collectively revealed a complex relationship between AMPK, mitochondrial dysfunction, and MS pathogenesis, with both cuprizone and experimental autoimmune encephalomyelitis models demonstrating associations between AMPK and mitochondrial disorders, including oxidative stress and impaired expression of mitochondrial genes. These studies illuminate the multifaceted role of AMPK in MS animal models, involving energy metabolism, inflammatory processes, oxidative stress, and gene regulation leading to mitochondrial dysfunction. However, unanswered questions about its mechanisms and clinical applications underscore the need for further research to fully harness its potential in addressing MS-related mitochondrial dysfunction.

Elevated exposures to fluoride have been linked to neurological diseases. Identifying mechanisms of fluoride neurotoxicity and finding ways for prevention and treatment of epidemic fluorosis are important issues of public health. In this study, fluoride inhibited TFEB nuclear translocation by activating p-mTORC1/p-p70S6K, thus inhibiting lysosomal biogenesis, leading to dysfunctional lysosome accumulation, which further negatively affected autophagosome and lysosome fusion, thus impairing autophagy degradation, evidenced by the blocked conversion of LC3II to LC3I, and the increased p62 levels. Interestingly, RSV alleviated rats' cognition by improving fluoride-induced nerve damage and promoted lysosomal biogenesis demonstrated by the increased nucleus translocation of TFEB via inhibiting p-mTORC1 and p-p70S6K, the decreased expression of LC3II and p62. Collectively, we clarified the correlation between fluoride neurotoxicity and mTORC1/TFEB-mediated lysosomal biogenesis and autophagy. Meanwhile, RSV appeared to be a promising drug for the prevention and treatment of epidemic fluorosis.

At present, meteorin-like protein (METRNL) has been proven to be widely expressed in the myocardium and participates in the pathogenic process of various cardiovascular diseases. However, the effects of METRNL on pathological cardiac hypertrophy is still unknown. In the present study, we used a mouse model of transverse aortic constriction (TAC) surgery to mimic pathological cardiac hypertrophy and gene delivery system to overexpress METRNL in vivo. The results showed that METRNL overexpression improved TAC-induced pathological cardiac hypertrophy in mice and neonatal cardiomyocytes. In addition, METRNL overexpression diminished TAC-induced cardiac oxidative damage, inflammation and cardiomyocyte apoptosis. Moreover, the cardioprotective effect of METRNL overexpression was directly related to the activation of AMP-activated protein kinase (AMPK) and sirtuin1 (SIRT1). In summary, our data identified that METRNL may be a promising therapeutic target to mitigate pathological cardiac hypertrophy in the future.

Mother's milk contains a unique microbiome that plays a relevant role in offspring health. We hypothesize that maternal malnutrition during lactation might impact the microbial composition of milk and affect adequate offspring gut colonization, increasing the risk for later onset diseases. Then, Wistar rats were fed ad libitum (Control, C) food restriction (Undernourished, U) during gestation and lactation. After birth, offspring feces and milk stomach content were collected at lactating day (L)4, L14 and L18. The V3-V4 region of the bacterial 16S rRNA gene was sequenced to characterize bacterial communities. An analysis of beta diversity revealed significant disparities in microbial composition between groups of diet at L4 and L18 in both milk, and fecal samples. In total, 24 phyla were identified in milk and 18 were identified in feces, with Firmicutes, Proteobacteria, Actinobacteroidota and Bacteroidota collectively representing 96.1% and 97.4% of those identified, respectively. A higher abundance of Pasteurellaceae and Porphyromonas at L4, and of Gemella and Enterococcus at L18 were registered in milk samples from the U group. Lactobacillus was also significantly more abundant in fecal samples of the U group at L4. These microbial changes compromised the number and variety of milk-feces or feces-feces bacterial correlations. Moreover, increased offspring gut permeability and an altered expression of goblet cell markers TFF3 and KLF3 were observed in U pups. Our results suggest that altered microbial communication between mother and offspring through breastfeeding may explain, in part, the detrimental consequences of maternal malnutrition on offspring programming.