Gut-muscle axis mechanism of exercise prevention of sarcopenia.

Sarcopenia refers to an age-related systemic skeletal muscle disorder, which is characterized by loss of muscle mass and weakening of muscle strength. Gut microbiota can affect skeletal muscle through a variety of mechanisms. Gut microbiota present distinct features among elderly people and sarcopenia patients, including a decrease in microbial diversity, which might be associated with the quality and function of the skeletal muscle. There might be a gut-muscle axis; where gut microbiota and skeletal muscle may affect each other bi-directionally. Skeletal muscle can affect the biodiversity of the gut microbiota, and the latter can, in turn, affect the anabolism of skeletal muscle. This review examines recent studies exploring the relationship between gut microbiota and skeletal muscle, summarizes the effects of exercise on gut microbiota, and discusses the possible mechanisms of the gut-muscle axis.

Salivary Short-chain Fatty Acids (SCFAs) Are Viable Predictors of Early Changes in Systemic Health.

Short-chain fatty acids (SCFAs) are the metabolites identified in both the oral cavity and the gut. They play an important role in the triggering, development and progression of systemic diseases. SCFAs can alter the gut microbial components, intestinal epithelium and host immune system, and are also associated with cancer incidence. Salivary SCFAs, produced by the oral microbiome, are correlated with some oral diseases. The occurrence of systemic diseases associated with gut SCFAs is more clearly defined than oral SCFAs. Salivary SCFAs can enter the bloodstream directly via inflamed gingiva to cause continuous low-grade systemic inflammation. Hence, salivary SCFAs could be an indicator for the early diagnosis of systemic diseases. Furthermore, they provide a basis for understanding the oral-systemic axis driven through salivary SCFAs in the pathogenesis of several diseases.

Ningxiang Pig-Derived Parabacteroides distasonis HNAU0205 Alleviates ETEC-Induced Intestinal Apoptosis, Oxidative Damage, and Inflammation in Piglets.

Weaning is a critical stage in the growth and development of piglets, often inducing stress reactions. This study aims to investigate the effects of Parabacteroides distasonis (PBd) derived from Ningxiang pigs on growth performance, intestinal apoptosis, oxidative damage, and inflammation in ETEC-challenged weaned piglets. A total of 22 Duroc × Landrace × Yorkshire (DLY) piglets, 24 days old with similar body weights, were randomly divided into three groups: Control (n = 7), ETEC (n = 7), and PBd + ETEC (n = 8). The results show that, compared to the Control group, ETEC challenge led to decreased growth performance, reduced villus height in the duodenum and jejunum, increased crypt depth in the duodenum, a decreased villus-height-to-crypt-depth ratio, increased expression of apoptosis-related genes (Caspase-8 and Caspase-9), increased expression of oxidative damage-related genes (Nrf2, GSH-PX, mTOR, and Beclin1), increased expression of inflammation-related genes (Myd88, P65, TNF-α, and IL-6), and reduced the contents of SCFAs in the colonic chyme (acetate, propionate, butyrate, valerate, and total SCFAs). Compared to the ETEC group, the PBd + ETEC group alleviated the reduction in growth performance, mitigated intestinal morphological damage, and reduced the expression of the aforementioned apoptosis, oxidative damage, and inflammation-related genes with the increase in SCFAs. In conclusion, PBd derived from Ningxiang pigs effectively reduces ETEC-induced intestinal damage in weaned piglets, improves intestinal health, and increases the content of SCFAs in the colonic chyme, thereby enhancing growth performance.

Black ginseng: a novel medicine for treating heart failure.

Introduction: Black ginseng (BG) was processed by "steaming and drying" (generally nine times) repeatedly to produce "rare saponins" and secondary ginsenosides. Both ginseng (GS) and red ginseng (RG) were commonly used in treating heart failure (HF), and the latter was confirmed to be more potent, implying the presence of rare ginsenosides that contribute positively to the treatment of heart failure. Previous research indicated that rare ginsenosides are more abundant in BG than in RG. Consequently, this study aims to investigate the effects of BG and its components on HF to elucidate the active substances and their underlying mechanisms in the treatment of HF. Methods: The effects of BG and its fractions (water-eluted fraction (WEF), total saponin fraction (TSF), and alcohol-eluted fraction (AEF)) on rats with isoproterenol (ISO)-induced HF were explored, and steroids belonging to the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were determined quantitatively using the ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method. In addition, 16S rDNA sequencing was performed on the gut microbiota, followed by GC-MS analysis of short-chain fatty acids (SCFAs), and the biochemical indexes related to energy metabolism and the serum cyclic nucleotide system were also analyzed by ELISA. Results: Based on a thorough evaluation of energy metabolism and the endocrine system, it was observed that the effects of BG components on the hypothalamic-pituitary-thyroid (HPT) and HPA axes were more pronounced. Notably, the treatment efficacy of the low dose of the total saponin fraction (TSFL), water decoction (WD), and high dose of the polysaccharide fraction (PSFH) was superior based on pharmacodynamic indicators such as brain natriuretic peptide (BNP), creatine kinase (CK), and estradiol (E2)/T). Furthermore, the WD and BG components exhibited significant effects on androgens (T and androstenedione (A4)). The TSFL group exerts an anti-inflammatory effect by regulating Lactobacillus/Erysipelotrichales. The WD, PSFH, and TSFL may impact inflammatory cytokines through the gut microbiota (Lactobacillus/Erysipelotrichales) and their metabolites (acetate and butyrate), exerting an anti-inflammatory effect. Discussion: The BG and all its split components demonstrated varying levels of efficacy in alleviating HF, and TSF and PSF exhibited a significant protective effect on HF. The main active components in TSF were revealed to be ginsenosides Rk1, Rk3, 20-(S)-Rg3, and 20-(S)-Rh2 by the H9C2 cell experiment. The decoction of BG and its components exhibited a potent impact on androgen hormones, with an elevation trend. This phenomenon may be attributed to the activation of the eNOS-NO pathway through androgen regulation, thereby contributing to its anti-HF activities. The WD, PSFH, and TSFL may exert anti-inflammatory effects through the intestinal flora (Lactobacillaceae/Erysipelotrichaceae) and its metabolites (acetic acid and butyric acid), which affect the inflammatory factors. The different mechanisms of action of each component of HF also reflect the significance and necessity of the overall role of traditional Chinese medicine (TCM). Our research was the first to report that the E2/T is related to HF and can be used as an indicator to evaluate HF.

The intestinal microbiome of infants with cow's milk-induced FPIES is enriched in taxa and genes of enterobacteria.

OBJECTIVES: Food protein-induced enterocolitis syndrome (FPIES) is a severe type of non-IgE (immunoglobulin E)-mediated (NIM) food allergy, with cow's milk (CM) being the most common offending food. The relationship between the gut microbiota and its metabolites with the inflammatory process in infants with CM FPIES is unknown, although evidence suggests a microbial dysbiosis in NIM patients. This study was performed to contribute to the knowledge of the interaction between the gut microbiota and its derived metabolites with the local immune system in feces of infants with CM FPIES at diagnosis. METHODS: Twelve infants with CM FPIES and a matched healthy control group were recruited and the gut microbiota was investigated by 16S amplicon and shotgun sequencing. Fatty acids (FAs) were measured by gas chromatography, while immune factors were determined by enzyme-linked immunosorbent assay and Luminex technology. RESULTS: A specific pattern of microbiota in the gut of CM FPIES patients was found, characterized by a high abundance of enterobacteria. Also, an intense excretion of FAs in the feces of these infants was observed. Furthermore, correlations were found between fecal bifidobacteria and immune factors. CONCLUSION: These fecal determinations may be useful to gain insight into the pathophysiology of this syndrome and should be taken in consideration for future studies of FPIES patients.

The impact of consuming different types of high-caloric fat diet on the metabolic status, liver, and aortic integrity in rats.

Consumption of high-caloric diets contributes to the alarming number of overweight and obese individuals worldwide, which in turn leads to several diseases and multiple organ dysfunction. Not only has the number of calories taken per day but also the type of fat in the diet has an important impact on health. Accordingly, the purpose of the current study was to examine the impact of different types of high-caloric fat diets on the metabolic status and the integrity of the liver and aorta in albino rats. Adult male albino rats were divided into 6 groups: Control group, long chain-saturated fat group (SFD), long chain-monounsaturated fat (MUFAs) group, long chain-polyunsaturated fat (PUFAs) group, medium-chain fat (MCFAs) group, and short-chain fat (SCFAs) group. Body mass index (BMI), Lee index, and visceral fat amount were reported. Serum levels of insulin, liver transaminases, lipid profile, and different oxidative stress and inflammatory markers were evaluated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and adiponectin/leptin ratio were also calculated. Histopathological examinations of liver and aorta with Masson's trichrome stain, and immune-staining for Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) were also done. SFD group showed significantly elevated liver transaminases, inflammatory markers, HOMA-IR, dyslipidemia, reduced adiponectin, and deficient anti-oxidative response compared to other groups together with disturbed hepatic and aortic architecture. Other treated groups showed an improvement. PUFAs group showed the highest level of improvement. Not all high-fat diets are hazardous. Diets rich in PUFAs, MUFAs, MCFAs, or SCFAs may protect against the hazards of high caloric diet.

Combination of magnetite and sodium percarbonate to enhance acetate-enriched short-chain fatty acids production during sludge anaerobic fermentation.

Large amounts of waste activated sludge are generated daily worldwide, posing significant environmental challenges. Anaerobic fermentation is a promising method for sludge disposal, but it has two technical bottlenecks: the availability of short-chain fatty acids (SCFAs)-producing substrates and SCFAs consumption by methanogenesis. This study proposes a pretreatment strategy combining sodium percarbonate (SPC) and magnetite (Fe3O4) to address these issues. Under optimized conditions (20 mg Fe3O4/g TSS and 15 mg SPC/g TSS), SCFAs production increased to 3244.10 ± 216.31 mg COD/L, about 3.06 times the control (1057.29 ± 35.06 mg COD/L) and surpassing reported treatments. The combined pretreatment enhanced the disruption of extracellular polymeric substances, increased the release of biodegradable matters, improved acidogenesis enzyme activities, and inhibited methanogenesis. Additionally, it increased NH4+-N release in favor of the recovery of phosphorus from sludge residual. This study demonstrates an efficient pretreatment for high SCFAs production and resource recovery from WAS.

In vitro digestion and fermentation characteristics of soluble dietary fiber from adlay (Coix lacryma-jobi L. var. ma-yuen Staft) bran modified by steam explosion.

Adlay bran is known for its nutrient-rich profile and multifunctional properties, and steam explosion (SE) is an emerging physical modification technique. However, the specific effects of SE on the activity composition and antioxidant capacity of adlay bran soluble dietary fiber (SDF) during in vitro digestion, as well as its influence on gut microbiota during in vitro fermentation, remain inadequately understood. This paper reports the in vitro digestion and fermentation characteristics of soluble dietary fiber from adlay bran modified by SE (SE-SDF). Compared with the untreated samples (0-SDF), most of the phenolic compounds and antioxidant capacity were significantly increased in the SE-SDF digests. Additionally, SE was beneficial for adlay bran SDF to increase the content of acetic acid, propionic acid and total short-chain fatty acids (SCFAs) in fermentation broth during in vitro fermentation. SE-SDF could promote the growth of beneficial bacteria while inhibiting the proliferation of pathogenic microbes. Our research indicates that SE-SDF shows strong antioxidant properties after in vitro digestion and plays a pivotal role in regulating gut microbiota during in vitro fermentation, ultimately enhancing human intestinal health.

Shenling Baizhu powder attenuates lard diet in a fatigued state-induced diarrhea via targeting microbial metabolites short chain fatty acids-mediated lipid metabolism.

Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM) prescription renowned for its efficacy, is specifically recognized for its therapeutic effects in managing diarrhea associated with spleen qi deficiency. Our previous research has demonstrated that a lard diet in a fatigued state induced diarrhea belonging to spleen qi deficiency in TCM. Through a comprehensive investigation, we aimed to provide insights into the intricate relationship between SLBZP and the modulation of gut microbiota in alleviating symptoms associated with spleen qi deficiency-induced diarrhea. We induced diarrhea in mice by subjecting them to continuous standing on a multiple-platform apparatus while administering lard through intragastric administration for 14 days. Subsequently, we conducted gavage administration of SLBZP at a concentration of 0.637 g/ml for seven days. We observed a therapeutic effect of SLBZP on diarrhea induced by a lard diet in a fatigued state. SLBZP mitigated disorders in lipid metabolism and diminished hepatic oxidative responses. Additionally, SLBZP reversed gut microbiota dysbiosis of diarrheic mice and notably increased the production of short-chain fatty acids (SCFAs), primarily acetic acid, butyric acid, and valeric acid. Through correlation analysis, we additionally identified Lactobacillus reuteri and Lactobacillus intestinalis as potentially pivotal species associated with the therapeutic effects of SLBZP. We demonstrated that SLBZP exerts therapeutic effects on diarrhea caused by a lard diet in a fatigued state by repairing the intestinal mucosal barrier, improving lipid metabolism disorders, and regulating gut microbiota and metabolites SCFAs.

Advances in the mechanism of action of short-chain fatty acids in psoriasis.

Psoriasis is a prevalent chronic inflammatory and immunological disorder. Its lesions are present as scaly erythema or plaques. Disruptions in the body's immune system play a significant role in developing psoriasis. Recent evidence suggests a potential role of the gut microbiome in autoimmune diseases. Short-chain fatty acids (SCFAs) are the primary metabolites created by gut microbes and play a crucial fuction in autoimmunity. SCFAs act on various cells by mediating signaling to participate in host physiological and pathological processes. These processes encompass body metabolism, maintenance of intestinal barrier function, and immune system modulation. SCFAs can regulate immune cells to enhance the body's immune function, potentially influencing the prevention and treatment of psoriasis. However, the mechanisms underlying the role of SCFAs in psoriasis remain incompletely understood. This paper examines the relationship between SCFAs and psoriasis, elucidating how SCFAs influence the immune system, inflammatory response, and gut barrier in psoriasis. According to the study, in psoriasis, SCFAs have been shown to regulate neutrophils, macrophages, and dendritic cells in the adaptive immune system, as well as T and B cells in the innate immune system. Additionally, we explore the role of SCFAs in psoriasis by maintaining intestinal barrier function, restoring intestinal ecological homeostasis, and investigating the potential therapeutic benefits of SCFAs for psoriasis.

Two-Year Study on the Intra-Individual Dynamics of Gut Microbiota and Short-Chain Fatty Acids Profiles in Healthy Adults.

While the gut microbiome has been intensively investigated for more than twenty years already, its role in various disorders remains to be unraveled. At the same time, questions about what changes in the gut microbiota can be considered as normal or pathological and whether communities are able to recover after exposure to negative factors (diseases, medications, environmental factors) are still unclear. Here, we describe changes in the gut microbiota composition and the content of short-chain fatty acids in adult healthy volunteers (n = 15) over a 24 month-period. Intraindividual variability in gut microbial composition was 40%, whereas the short chain fatty acids profile remained relatively stable (2-year variability 20%, inter-individual 26%). The changes tend to accumulate over time. Nevertheless, both short-term and long-term changes in the gut microbiome composition were significantly smaller within individuals than interindividual differences (two-year interindividual variability was 75%). Seasonal changes in gut microbiota were found more often in autumn and spring involving the content of minor representatives (less than 1.5% of the community in average) in the phyla Actinobacteriota, Firmicutes and Proteobacteria.

Interconnections between the Gut Microbiome and Alzheimer's Disease: Mechanisms and Therapeutic Potential.

Alzheimer's disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-ß (Aß) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The Aß monoclonal antibody lecanemab reduces Aß plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood-brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.

The Role of the Gut Microbiota in Sanfilippo Syndrome's Physiopathology: An Approach in Two Affected Siblings.

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes (SusA, SusB, SusE, and SusG) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients.

Non-SCFA microbial metabolites associated with fiber fermentation and host health.

Dietary fiber is degraded by commensal gut microbes to yield host-beneficial short-chain fatty acids (SCFAs), but personalized responses to fiber supplementation highlight a role for other microbial metabolites in shaping host health. In this review we summarize recent findings from dietary fiber intervention studies describing health impacts attributed to microbial metabolites other than SCFAs, particularly secondary bile acids (2°BAs), aromatic amino acid derivatives, neurotransmitters, and B vitamins. We also discuss shifts in microbial metabolism occurring through altered maternal dietary fiber intake and agricultural practices, which warrant further investigation. To optimize the health benefits of dietary fibers, it is essential to survey a range of metabolites and adapt recommendations on a personalized basis, according to the different functional aspects of the microbiome.

Gut-Derived Short-Chain Fatty Acids and Macrophage Modulation: Exploring Therapeutic Potentials in Pulmonary Fungal Infections.

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, modulate immune cell functions, particularly macrophages. This review explores the potential therapeutic applications of SCFAs in pulmonary fungal infections, a critical concern due to their high mortality rates and antifungal resistance. SCFAs enhance macrophage functions by promoting phagosome-lysosome fusion, increasing reactive oxygen species production, and balancing cytokine responses. Pulmonary fungal infections, caused by pathogens like Aspergillus fumigatus, are prevalent in immunocompromised patients, including those with diabetes, chronic obstructive pulmonary disease, and those on high-dose corticosteroids. SCFAs have shown promise in improving macrophage function in these contexts. However, the application of SCFAs must be balanced against potential side effects, including gut microbiota disruption and metabolic disorders. Further research is needed to optimize SCFA therapy for managing pulmonary fungal infections.

Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling.

As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.

Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity.

Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs' production could play a fundamental role in cancer immunotherapy.

Alginate oligosaccharide improves 5-fluorouracil-induced intestinal mucositis by enhancing intestinal barrier and modulating intestinal levels of butyrate and isovalerate.

Chemotherapy-induced mucositis (CIM) is the typical side effect of chemotherapy. This study investigates the potential of alginate oligosaccharide (AOS) in ameliorating CIM induced by 5-fluorouracil (5-FU) in a murine model and its underlying mechanisms. AOS effectively mitigated body weight loss and histopathological damage, modulated inflammatory cytokines and attenuated the oxidative stress. AOS restored intestinal barrier integrity through enhancing expression of tight junction proteins via MLCK signaling pathway. AOS alleviated intestinal mucosal damage by inhibiting TLR4/MyD88/NF-κB signaling pathway, downregulating the pro-apoptotic protein Bax and upregulating the anti-apoptotic protein Bcl-2. Moreover, AOS significantly enriched intestinal Akkermansiaceae and increased the production of short-chain fatty acids (SCFAs), most notably butyrate and isovalerate. Pre-treatment with butyrate and isovalerate also alleviated 5-FU-induced CIM. In conclusion, AOS effectively mitigated CIM through strenghthening intestinal barrier, attenuating inflammation, and modulating gut microbiota and intestianl levels of butyrate and isovalerate. These finding indicate that AOS could be potentially utilized as a supplemental strategy for prevention or mitigation of CIM.