Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition

Ling, Catriona; Versloot, Christian J.; Arvidsson Kvissberg, Matilda E.; Hu, Guanlan; Swain, Nathan; Horcas-Nieto, José M.; Miraglia, Emily; Thind, Mehakpreet K.; Farooqui, Amber; Gerding, Albert; van Eunen, Karen; Koster, Mirjam H.; Kloosterhuis, Niels J.; Chi, Lijun; ChenMi, YueYing; Langelaar-Makkinje, Miriam; Bourdon, Celine; Swann, Jonathan; Smit, Marieke; de Bruin, Alain; Youssef, Sameh A.; Feenstra, Marjon; van Dijk, Theo H.; Thedieck, Kathrin; Jonker, Johan W.; Kim, Peter K.; Bakker, Barbara M.; Bandsma, Robert H.J.

doi:10.1016/j.ebiom.2023.104809

Cited by 15 publications

(3 citation statements)

References 91 publications

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“…In the present study, we observed that maternal food restriction increased colonic permeability in the lactating offspring, as evidenced by a reduction in ZO-1 protein levels, which was not fully ameliorated when undernutrition was corrected postweaning [16]. In agreement, severe protein deficiency in animal models led to structural and functional changes of the intestine, including malabsorption and the development of a leaky gut with increased permeability [17,58]. Intestinal biopsies from severely undernourished children with enteropathy also showed a reduced expression of the tight junctions claudin-4 and E-cadherin [59], although the molecular mechanism relating undernutrition to changes in paracellular proteins remains unclear.…”

Section: Discussionsupporting

confidence: 76%

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats

Martínez-Oca,

Alba,

Sánchez-Roncero

et al. 2023

Nutrients

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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.

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Section: Discussionsupporting

confidence: 76%

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats

Martínez-Oca,

Alba,

Sánchez-Roncero

et al. 2023

Nutrients

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“…Increasing evidence has suggested that SIRT1 play a role in intestinal disease[ 30 ]. SIRT1 can regulate intestinal inflammation in aging mice by altering the gut microbiota[ 31 ], and achieve mitochondrial homeostasis through the NAD + -SIRT1 pathway to protect the intestinal barrier function in patients with severe malnourishment[ 32 ]. There are also reports emphasizing the dual role of SIRT1[ 33 ]; SIRT1 inhibitors can alleviate radiation-induced intestinal stem cell death, promote crypt recovery, and improve the survival rate of mice[ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

Chen,

Wang,

Chen

et al. 2024

World J Gastroenterol

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BACKGROUND 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. AIM To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS 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 immunohistochemical 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 were 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. RESULTS 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. CONCLUSION 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.

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“…The interconnection of the NAD+, AMPK, and SIRT1 pathways presents a promising avenue for understanding and manipulating the complex molecular interactions underlying demyelinating diseases (Wang et al, 2016). In a related context, SIRT1, an NAD+‐dependent protein deacetylase essential for mitochondrial biogenesis (Ling et al, 2023), exhibited reduced expression in the spinal cords of EAE patients. LOVA and AICAR treatments partially restored SIRT1 levels, and the combination treatment fully restored SIRT1 expression.…”

Section: Discussionmentioning

confidence: 99%

AMP‐activated protein kinase as a mediator of mitochondrial dysfunction of multiple sclerosis in animal models: A systematic review

Askari,

Rabiei,

Lohrasbi

et al. 2024

Journal Cellular Physiology

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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.

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Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition

Cited by 15 publications

References 91 publications

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats

Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway

AMP‐activated protein kinase as a mediator of mitochondrial dysfunction of multiple sclerosis in animal models: A systematic review

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