-
Nutrients Jan 2024The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel... (Review)
Review
The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.
Topics: Humans; Irritable Bowel Syndrome; FODMAP Diet; Fermentation; Disaccharides; Oligosaccharides; Diet; Monosaccharides; Diet, Carbohydrate-Restricted
PubMed: 38337655
DOI: 10.3390/nu16030370 -
Science Advances Dec 2023Stress coping involves innate and active motivational behaviors that reduce anxiety under stressful situations. However, the neuronal bases directly linking stress,...
Stress coping involves innate and active motivational behaviors that reduce anxiety under stressful situations. However, the neuronal bases directly linking stress, anxiety, and motivation are largely unknown. Here, we show that acute stressors activate mouse GABAergic neurons in the interpeduncular nucleus (IPN). Stress-coping behavior including self-grooming and reward behavior including sucrose consumption inherently reduced IPN GABAergic neuron activity. Optogenetic silencing of IPN GABAergic neuron activation during acute stress episodes mimicked coping strategies and alleviated anxiety-like behavior. In a mouse model of stress-enhanced motivation for sucrose seeking, photoinhibition of IPN GABAergic neurons reduced stress-induced motivation for sucrose, whereas photoactivation of IPN GABAergic neurons or excitatory inputs from medial habenula potentiated sucrose seeking. Single-cell sequencing, fiber photometry, and optogenetic experiments revealed that stress-activated IPN GABAergic neurons that drive motivated sucrose seeking express somatostatin. Together, these data suggest that stress induces innate behaviors and motivates reward seeking to oppose IPN neuronal activation as an anxiolytic stress-coping mechanism.
Topics: Animals; Mice; Motivation; Anxiety; GABAergic Neurons; Reward; Sucrose
PubMed: 38055830
DOI: 10.1126/sciadv.adh9620 -
Nature Microbiology Nov 2023Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions,...
Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.
Topics: Humans; Mice; Animals; Lactulose; Hepatic Encephalopathy; Anti-Bacterial Agents
PubMed: 37845315
DOI: 10.1038/s41564-023-01493-w -
Pharmaceutics Aug 2023Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other... (Review)
Review
Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about 7 million Dalton (Da), equivalent to roughly 20,000 disaccharide monomers; although some sources report a lower range of 3-4 million Da. In recent years, HA has garnered significant attention in the field of rheumatology due to its involvement in joint lubrication, cartilage maintenance, and modulation of inflammatory and/or immune responses. This review aims to provide a comprehensive overview of HA's involvement in rheumatology, covering its physiology, pharmacology, therapeutic applications, and potential future directions for enhancing patient outcomes. Nevertheless, the use of HA therapy in rheumatology remains controversial with conflicting evidence regarding its efficacy and safety. In conclusion, HA represents a promising therapeutic option to improve joint function and alleviate inflammation and pain.
PubMed: 37765216
DOI: 10.3390/pharmaceutics15092247 -
Carbohydrate Research Nov 2023Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have... (Review)
Review
Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have considerable therapeutic potential, and are used as drugs in the treatment of diabetes and infectious diseases. The development of this branch of carbohydrate chemistry would not be possible without the development of novel methods for its synthesis and the analysis of their biochemical properties. In this Review Article, we summarize our findings on the biological properties of a collection of thio sugars and their derivatives synthesized by the Witczak and Bielski team using their original methods based on the Michael addition of sugar thiols to levoglucosenone.
Topics: Disaccharides; Thiosugars
PubMed: 37708795
DOI: 10.1016/j.carres.2023.108934 -
Indian Journal of Pediatrics Mar 2024Hepatic encephalopathy, characterized by mental status changes and neuropsychiatric impairment, is associated with chronic liver disease as well as acute liver failure.... (Review)
Review
Hepatic encephalopathy, characterized by mental status changes and neuropsychiatric impairment, is associated with chronic liver disease as well as acute liver failure. In children, its clinical manifestations can be challenging to pinpoint. However, careful assessment for the development of hepatic encephalopathy is imperative when caring for these patients as progression of symptoms can indicate impending cerebral edema and systemic deterioration. Hepatic encephalopathy can present with hyperammonemia, but it is important to note that the degree of hyperammonemia is not indicative of severity of clinical manifestations. Newer forms of assessment are undergoing further research, and include imaging, EEG and neurobiomarkers. Mainstay of treatment currently includes management of underlying cause of liver disease, as well as reduction of hyperammonemia with either enteral medications such as lactulose and rifaximin, or even with extracorporeal liver support modalities.
Topics: Child; Humans; Hepatic Encephalopathy; Hyperammonemia; Rifaximin; Lactulose; Drug Therapy, Combination; Liver Cirrhosis
PubMed: 37310582
DOI: 10.1007/s12098-023-04679-6 -
Nature Microbiology Sep 2023Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium...
Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium cell surfaces or mechanisms of phage resistance. We show here that trehalose polyphleates (TPPs)-high-molecular-weight, surface-exposed glycolipids found in some mycobacterial species-are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by clinically useful phages BPs and Muddy. TPP loss leads to defects in adsorption and infection and confers resistance. Transposon mutagenesis shows that TPP disruption is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insensitive due to TPP synthesis gene mutations. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.
Topics: Mycobacteriophages; Trehalose; Bacteriophages; Amino Acid Substitution; Cell Membrane
PubMed: 37644325
DOI: 10.1038/s41564-023-01451-6 -
International Journal of Molecular... Feb 2024Rosavin, a phenylpropanoid in 's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular... (Review)
Review
Rosavin, a phenylpropanoid in 's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.
Topics: Animals; Mice; Osteoclasts; Tartrate-Resistant Acid Phosphatase; Osteogenesis; Bone Resorption; Cell Differentiation; NF-kappa B; Metalloproteases; RANK Ligand; NFATC Transcription Factors; Disaccharides
PubMed: 38396794
DOI: 10.3390/ijms25042117 -
Plant Biotechnology Journal Oct 2023Sugar deficiency is the persistent challenge for plants during development. Trehalose-6-phosphate (T6P) is recognized as a key regulator in balancing plant sugar...
Sugar deficiency is the persistent challenge for plants during development. Trehalose-6-phosphate (T6P) is recognized as a key regulator in balancing plant sugar homeostasis. However, the underlying mechanisms by which sugar starvation limits plant development are unclear. Here, a basic helix-loop-helix (bHLH) transcription factor (OsbHLH111) was named starvation-associated growth inhibitor 1 (OsSGI1) and the focus is on the sugar shortage of rice. The transcript and protein levels of OsSGI1 were markedly increased during sugar starvation. The knockout mutants sgi1-1/2/3 exhibited increased grain size and promoted seed germination and vegetative growth, which were opposite to those of overexpression lines. The direct binding of OsSGI1 to sucrose non-fermenting-1 (SNF1)-related protein kinase 1a (OsSnRK1a) was enhanced during sugar shortage. Subsequently, OsSnRK1a-dependent phosphorylation of OsSGI1 enhanced the direct binding to the E-box of trehalose 6-phosphate phosphatase 7 (OsTPP7) promoter, thus rose the transcription inhibition on OsTPP7, then elevated trehalose 6-phosphate (Tre6P) content but decreased sucrose content. Meanwhile, OsSnRK1a degraded phosphorylated-OsSGI1 by proteasome pathway to prevent the cumulative toxicity of OsSGI1. Overall, we established the OsSGI1-OsTPP7-Tre6P loop with OsSnRK1a as center and OsSGI1 as forward, which is activated by sugar starvation to regulate sugar homeostasis and thus inhibits rice growth.
Topics: Sugars; Oryza; Trehalose; Plants; Sucrose; Phosphates; Gene Expression Regulation, Plant
PubMed: 37384619
DOI: 10.1111/pbi.14110 -
Proceedings of the National Academy of... Oct 2023Plant roots explore the soil for water and nutrients, thereby determining plant fitness and agricultural yield, as well as determining ground substructure, water levels,...
Plant roots explore the soil for water and nutrients, thereby determining plant fitness and agricultural yield, as well as determining ground substructure, water levels, and global carbon sequestration. The colonization of the soil requires investment of carbon and energy, but how sugar and energy signaling are integrated with root branching is unknown. Here, we show through combined genetic and chemical modulation of signaling pathways that the sugar small-molecule signal, trehalose-6-phosphate (T6P) regulates root branching through master kinases SNF1-related kinase-1 (SnRK1) and Target of Rapamycin (TOR) and with the involvement of the plant hormone auxin. Increase of T6P levels both via genetic targeting in lateral root (LR) founder cells and through light-activated release of the presignaling T6P-precursor reveals that T6P increases root branching through coordinated inhibition of SnRK1 and activation of TOR. Auxin, the master regulator of LR formation, impacts this T6P function by transcriptionally down-regulating the T6P-degrader trehalose phosphate phosphatase B in LR cells. Our results reveal a regulatory energy-balance network for LR formation that links the 'sugar signal' T6P to both SnRK1 and TOR downstream of auxin.
Topics: Arabidopsis; Trehalose; Sugar Phosphates; Indoleacetic Acids; Protein Serine-Threonine Kinases; Arabidopsis Proteins
PubMed: 37748053
DOI: 10.1073/pnas.2302996120