We previously performed animal studies that suggested that trehalose potentially prevents the development of metabolic syndrome in humans. To evaluate this possibility, we examined whether trehalose suppressed the progression of insulin resistance in a placebo-controlled, double-blind trial in 34 su …

Opportunistic bacterial infections amongst HIV-infected individuals contribute significantly to HIV-associated mortality. The role of HIV-mediated modulation of innate mechanisms like autophagy in promoting opportunistic infections, however, remains obscure. Here we show, HIV reactivation in or infe …

Currently, there is no proven causal association between the incidence or severity of human CDI and the presence of trehalose metabolism variants. Furthermore, microbial metabolism reduces trehalose bioavailability, potentially removing this competitive advantage for C. difficile trehalose metabolis …

Trehalose is a non-reducing disaccharide consisting of two glucose molecules linked by a 1–1 glycosidic bond. Trehalose can play a role in organ detoxification, antioxidant enzyme activity, reducing lipid peroxidation and reducing the secretion of inflammatory factors TNF-, IL-1β, Il-6, thereby inhibiting liver damage. Because of its role, this study aims to determine the effect of trehalose administration on liver damage through the IL-6 expression pathway with experimental post-test design with control group design. This research was conducted using samples of old rats, namely Wistar rats (Rattus novergicus). The old rats used were 21 male species which were then divided into 3 groups, namely the old control group, the old rat group that was given sucrose, and the old rat group that was given trehalose. Then observed for 8 weeks, namely in March - May 2021 at the Faculty of Medicine, Hasanuddin University Makassar. The results obtained from the 3 groups showed a significant value that the administration of trehalose sugar in elderly mice had an effect on reducing the inflammatory factor IL-6 because it activated autophagy in macrophages thereby reducing cytokine production and vascular inflammation so as to be able to restore all aging mice to a level like observed in young mice. It is also known that aged rat liver, which is characterized by ER UPR activation and inflammatory signaling, decreases nicotinamide and UDP-N-acetyl-hexosamines, and reduces proteasome activity. Therefore, trehalose can be an effective therapeutic strategy against age-related disorders of proteostasis in the liver.

Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice). A 2% trehalose solution was administered as drinking water during 24 days of the experiment. Expressions of markers of autophagy (LC3-II), neuroinflammation (IBA1), redox state (NOS), and neuronal density (NeuN) in the brain were assessed by immunohistochemical analysis. For behavioral phenotyping, the open field, elevated plus-maze, tail suspension, pre-pulse inhibition, and passive avoidance tests were used. Trehalose caused a slight reduction in increased blood glucose concentration, considerable autophagy activation, and a decrease in the neuroinflammatory response in the brain along with improvements of exploration, locomotor activity, anxiety, depressive-like behavior, and fear learning and memory in db/db mice. Trehalose exerted some beneficial peripheral and systemic effects and partially reversed behavioral alterations in db/db mice. Thus, trehalose as an inducer of mTOR-independent autophagy is effective at alleviating neuronal and behavioral disturbances accompanying experimental diabetes.

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Trehalose is added in drug formulations to act as fillers or improve aerosolization performance. Its characteristics as a carrier molecule have been e…

In this study, it was demonstrated that trehalose which was administered orally to aged rats for four weeks, upregulated SIRT1 in kidneys. In addition, trehalose attenuated lipid peroxidation and inf...

Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer’s disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice. Therefore, we here assessed the effects of continuous trehalose administration via drinking water using the mouse Spared Nerve Injury model of neuropathic pain. Trehalose had no effect on drinking, feeding, voluntary wheel running, motor coordination, locomotion, and open field, elevated plus maze, and Barnes Maze behavior, showing that it was well tolerated. However, trehalose reduced nerve injury-evoked nociceptive mechanical and thermal hypersensitivity as compared to vehicle. Trehalose had no effect on calcium currents in primary somatosensory neurons, pointing to central mechanisms of the antinociceptive effects. In IntelliCages, trehalose-treated mice showed reduced activity, in particular, a low frequency of nosepokes, which was associated with a reduced proportion of correct trials and flat learning curves in place preference learning tasks. Mice failed to switch corner preferences and stuck to spontaneously preferred corners. The behavior in IntelliCages is suggestive of sedative effects as a “side effect” of a continuous protracted trehalose treatment, leading to impairment of learning flexibility. Hence, trehalose diet supplements might reduce chronic pain but likely at the expense of alertness.

Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including Clostridioides difficile. Trehalose has been reported to enhance virulence of certain C. difficile ribotypes; ...

Mucopolysaccharidosis (MPS) consists of a group of 11 enzymatic defects which result in accumulation of undegraded glycosaminoglycans (GAG) in lysosomes. MPS is a severe metabolic disease for which only bone marrow/hematopoietic stem cell transplantation ...

Trehalose is a disaccharide of two D-glucose molecules linked by a glycosidic linkage, which plays both structural and functional roles in bacteria. Trehalose can be synthesized and degraded by several pathways, and induction of trehalose biosynthesis ...

Spinal cord injury (SCI) is a major cause of irreversible nerve injury and leads to serious tissue loss and neurological dysfunction. Thorough investigation of cellular mechanisms, such as autophagy, is crucial for developing novel and effective therapeutics. We administered trehalose, an mTOR-independent autophagy agonist, in SCI rats suffering from moderate compression injury to elucidate the relationship between autophagy and SCI and evaluate trehalose’s therapeutic potential. 60 rats were divided into 4 groups and were treated with either control vehicle, trehalose, chloroquine, or trehalose + chloroquine 2 weeks prior to administration of moderate spinal cord crush injury. 20 additional sham rats were treated with control vehicle. H&E staining, Nissl staining, western blot, and immunofluorescence studies were conducted to examine nerve morphology and quantify autophagy and mitochondrial-dependent apoptosis at various time points after surgery. Functional recovery was assessed over a period of 4 weeks after surgery. Trehalose promotes autophagosome recruitment via an mTOR-independent pathway, enhances autophagy flux in neurons, inhibits apoptosis via the intrinsic mitochondria-dependent pathway, reduces lesion cavity expansion, decreases neuron loss, and ultimately improves functional recovery following SCI (all ). Furthermore, these effects were diminished upon administration of chloroquine, an autophagy flux inhibitor, indicating that trehalose’s beneficial effects were due largely to activation of autophagy. This study presents new evidence that autophagy plays a critical neuroprotective and neuroregenerative role in SCI, and that mTOR-independent activation of autophagy with trehalose leads to improved outcomes. Thus, trehalose has great translational potential as a novel therapeutic agent after SCI.

Machado-Joseph disease (MJD) is relatively prevalent among the Yemenite Jewish subpopulation living in Israel. Currently, there is no treatment able to modify the disease progression. Trehalose is a disaccharide with protein-stabilizing and autophagy-enhancing properties. In animal models of MJD, tr …

Trehalose is a disaccharide and fasting-mimetic that has been both canonized and vilified for its putative cardiometabolic and microbial effects. Trehalose analogues are currently under development to extend the key metabolic therapeutic actions of trehalose ...

What is fidaxomicin? (Dificid/Dificlr) Why is it effective against C Difficile? Find out more about the drug and the disease here

Fidaxomicin has been scrutinized because of its high acquisition cost. Real-world experience is needed to determine whether fidaxomicin has value in patients with Clostridium difficile–associated diarrhea (CDAD) and certain risk factors.In this ...

The consumption of dietary supplements and cold therapies containing high concentrations of zinc is now being called into question, following research that suggests it may worsen Clostridium difficile infection.

Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low conce …

Two hypervirulent ribotypes of the enteric pathogen Clostridium difficile, RT027 and RT078, have independently acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose, suggesting a correlation between the emergence of these ribotypes and the widespread adoption of trehalose in the human diet.

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This Medical News article discusses whether trehalose, a sugar manufactured from cornstarch used to sweeten and texturize foods, has contributed to the emergence of epidemic strains of Clostridium difficile infection (CDI).

Learn more about this infectious disease that is becoming more common and often affects older adults in a health care facility, often after antibiotic use.

C-diff is a bacterium that causes a life-threatening infection. Though the bacterium can infect healthy individuals, it is of particular concern to those who are hospitalized or are taking

The increasing frequency and severity of healthcare-associated outbreaks caused by bacterium Clostridium difficile have been linked to the widely used...

Rough notes from the webinar The Scientist: Precision Medicine Learning Lessons from the Microbiome (now available online)

c ribotypes of C. difficile harbour mutations or have acquired extra genes that mean these strains can utilize lower concentrations of bioavailable trehalose, providing a competitive metabolic advantage in some CDI animal models. By contrast, evidence has emerged to show that trehalose-induced microbiota changes can help protect/reduce CDI in other models. In addition, C. difficile trehalose metabolic variants are widespread among epidemic and nonepidemic ribotypes alike, and the occurrence of these trehalose variants was not associated with increase disease severity or mortality. Summary Currently, there is no proven causal association between the incidence or severity of human CDI and the presence of trehalose metabolism variants. Furthermore, microbial metabolism reduces trehalose bioavailability, potentially removing this competitive advantage for C. difficile trehalose metabolism variants. Taken together, trehalose consumed as part of a normal diet has no increased risk of CDI....