Mitocentricity.

Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, mitochondria are conditionally placed in a certain cellular center, which is responsible for both energy production and other non-energetic functions, without which the existence of not only the eukaryotic cell itself, but also the entire organism is impossible. Taking into account the high multifunctionality of mitochondria, such a fundamentally new scheme of cell functioning organization, including mitochondrial management of processes that determine cell survival and death, may be justified. Considering that this issue is dedicated to the memory of V. P. Skulachev, who can be called mitocentric, due to the history of his scientific activity almost entirely aimed at studying mitochondria, this work examines those aspects of mitochondrial functioning that were directly or indirectly the focus of attention of this outstanding scientist. We list all possible known mitochondrial functions, including membrane potential generation, synthesis of Fe-S clusters, steroid hormones, heme, fatty acids, and CO2. Special attention is paid to the participation of mitochondria in the formation and transport of water, as a powerful biochemical cellular and mitochondrial regulator. The history of research on reactive oxygen species that generate mitochondria is subject to significant analysis. In the section "Mitochondria in the center of death", special emphasis is placed on the analysis of what role and how mitochondria can play and determine the program of death of an organism (phenoptosis) and the contribution made to these studies by V. P. Skulachev.

Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.

Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.

The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c+ cells mainly representing neutrophils and macrophages using cell sorting. We also evaluated the severity of AKI during synaptamide therapy and the serum metabolic profile. We demonstrated that synaptamide reduced the level of pro-inflammatory interleukins and the expression of integrin CD11a in kidney tissue after injury. We found that the administration of synaptamide increased the expression of its receptor GPR110 in both total kidney tissue and renal CD11b/c+ cells that was associated with the reduced production of pro-inflammatory interleukins in these cells. Thus, we demonstrated that synaptamide therapy mitigates the inflammatory response in kidney tissue during ischemic AKI, which can be achieved through GPR110 signaling in neutrophils and a reduction in these cells' pro-inflammatory interleukin production.

The effects of antibiotic therapy on neonatal sepsis-associated acute kidney injury.

AIM: Neonatal sepsis remains one of the most dangerous conditions in the neonatal intensive care units. One of the organs affected by sepsis is the kidney, making acute kidney injury (AKI) a common complication of sepsis. Treatment of sepsis almost always involves antibiotic therapy, which by itself may cause some adverse effects, including nephrotoxicity. We analyzed the mutual effect of antibiotic therapy and sepsis on AKI in an experimental and clinical study in infants and neonatal rats. MATERIALS AND METHODS: We evaluated the influence of therapy with different antibiotics on the appearance of AKI markers (blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), clusterin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), calbindin, glutation-S-transferase subtype π (GST-π)) and liver injury markers in newborns with or without clinical signs of sepsis in the intensive care unit. In parallel, we analyzed the development of AKI in experimental lipopolysaccharide (LPS)-induced systemic inflammation in newborn rats accompanied by antibiotic therapy. KEY FINDINGS: We showed that therapy with metronidazole or ampicillin in combination with sulbactam had a beneficial effect in children with suspected sepsis, resulting in a decrease in AKI markers levels. However, treatment of newborns with netilmicin, cefepime, linezolid, or imipenem in combination with cilastatin worsened kidney function in these patients. SIGNIFICANCE: This prospective study indicates which antibiotics are preferable in neonatal sepsis and which should be used with caution in view of the risk of AKI development.

Mitochondrial Network: Electric Cable and More.

Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell. This analytical review gives the history of the cable theory, lists unsolved critical problems, describes the restructuring of the mitochondrial network and the role of oxidative stress in this process. In addition to the already proven functioning of extended mitochondrial structures as electrical cables, a number of additional functions are proposed, in particular, the hypothesis is put forth that mitochondrial networks maintain the redox potential in the cellular volume, which may vary depending on the physiological state, as a result of changes in the three-dimensional organization of the mitochondrial network (fragmentation/fission-fusion). A number of pathologies accompanied by a violation of the redox status and the participation of mitochondria in them are considered.

Biomarkers of the End-Stage Renal Disease Progression: Beyond the GFR.

Chronic kidney disease can progress to the end-stage renal disease (ESRD) characterized by a high risk of morbidity and mortality. ESRD requires immediate therapy or even dialysis or kidney transplantation, therefore, its timely diagnostics is critical for many patients. ESRD is associated with pathological changes, such as inflammation, fibrosis, endocrine disorders, and epigenetic changes in various cells, which could serve as ESRD markers. The review summarizes information on conventional and new ESRD biomarkers that can be assessed in kidney tissue, blood, and urine. Some biomarkers are specific to a particular pathology, while others are more universal. Here, we suggest several universal inflammatory, fibrotic, hormonal, and epigenetic markers indicative of severe deterioration of renal function and ESRD progression for improvement of ESRD diagnostics.

Fine Structure of Plasmodesmata-Associated Membrane Bodies Formed by Viral Movement Protein.

Cell-to-cell transport of plant viruses through plasmodesmata (PD) requires viral movement proteins (MPs) often associated with cell membranes. The genome of the Hibiscus green spot virus encodes two MPs, BMB1 and BMB2, which enable virus cell-to-cell transport. BMB2 is known to localize to PD-associated membrane bodies (PAMBs), which are derived from the endoplasmic reticulum (ER) structures, and to direct BMB1 to PAMBs. This paper reports the fine structure of PAMBs. Immunogold labeling confirms the previously observed localization of BMB1 and BMB2 to PAMBs. EM tomography data show that the ER-derived structures in PAMBs are mostly cisterns interconnected by numerous intermembrane contacts that likely stabilize PAMBs. These contacts predominantly involve the rims of the cisterns rather than their flat surfaces. Using FRET-FLIM (Förster resonance energy transfer between fluorophores detected by fluorescence-lifetime imaging microscopy) and chemical cross-linking, BMB2 is shown to self-interact and form high-molecular-weight complexes. As BMB2 has been shown to have an affinity for highly curved membranes at cisternal rims, the interaction of BMB2 molecules located at rims of adjacent cisterns is suggested to be involved in the formation of intermembrane contacts in PAMBs.

Fibrosis Development Linked to Alterations in Glucose and Energy Metabolism and Prooxidant-Antioxidant Balance in Experimental Models of Liver Injury.

The development of liver fibrosis is one of the most severe and life-threatening outcomes of chronic liver disease (CLD). For targeted therapy of CLD, it is highly needed to reveal molecular targets for normalizing metabolic processes impaired in damaged liver and associated with fibrosis. In this study, we investigated the morphological and biochemical changes in rat liver models of fibrosis induced by chronic administration of thioacetamide, carbon tetrachloride, bile duct ligation (BDL), and ischemia/reperfusion (I/R), with a specific focus on carbohydrate and energy metabolism. Changes in the levels of substrates and products, as well as enzyme activities of the major glucose metabolic pathways (glycolysis, glucuronidation, and pentose phosphate pathway) were examined in rat liver tissue after injury. We examined key markers of oxidative energy metabolism, such as the activity of the Krebs cycle enzymes, and assessed mitochondrial respiratory activity. In addition, pro- and anti-oxidative status was assessed in fibrotic liver tissue. We found that 6 weeks of exposure to thioacetamide, carbon tetrachloride, BDL or I/R resulted in a decrease in the activity of glycolytic enzymes, retardation of mitochondrial respiration, elevation of glucuronidation, and activation of pentose phosphate pathways, accompanied by a decrease in antioxidant activity and the onset of oxidative stress in rat liver. Resemblance and differences in the changes in the fibrosis models used are described, including energy metabolism alterations and antioxidant status in the used fibrosis models. The least pronounced changes in glucose metabolism and mitochondrial functions in the I/R and thioacetamide models were associated with the least advanced fibrosis. Ultimately, liver fibrosis significantly altered the metabolic profile in liver tissue and the flux of glucose metabolic pathways, which could be the basis for targeted therapy of liver fibrosis in CLD caused by toxic, cholestatic, or I/R liver injury.

Ketogenic Diet and Ketone Bodies against Ischemic Injury: Targets, Mechanisms, and Therapeutic Potential.

The ketogenic diet (KD) has been used as a treatment for epilepsy since the 1920s, and its role in the prevention of many other diseases is now being considered. In recent years, there has been an intensive investigation on using the KD as a therapeutic approach to treat acute pathologies, including ischemic ones. However, contradictory data are observed for the effects of the KD on various organs after ischemic injury. In this review, we provide the first systematic analysis of studies conducted from 1980 to 2022 investigating the effects and main mechanisms of the KD and its mimetics on ischemia-reperfusion injury of the brain, heart, kidneys, liver, gut, and eyes. Our analysis demonstrated a high diversity of both the composition of the used KD and the protocols for the treatment of animals, which could be the reason for contradictory effects in different studies. It can be concluded that a true KD or its mimetics, such as ß-hydroxybutyrate, can be considered as positive exposure, protecting the organ from ischemia and its negative consequences, whereas the shift to a rather similar high-calorie or high-fat diet leads to the opposite effect.

New experimental model of kidney injury: Photothrombosis-induced kidney ischemia.

Acute kidney injury (AKI) is a frequent pathology with a high mortality rate after even a single AKI episode and a great risk of chronic kidney disease (CKD) development. To get insight into mechanisms of the AKI pathogenesis, there is a need to develop diverse experimental models of the disease. Photothrombosis is a widely used method for inducing ischemia in the brain. In this study, for the first time, we described photothrombosis-induced kidney ischemia as an appropriate model of AKI and obtained comprehensive characteristics of the photothrombotic lesion using micro-computed tomography (micro-CT) and histological techniques. In the ischemic area, we observed destruction of tubules, the loss of brush border and nuclei, connective tissue fibers disorganization, leukocyte infiltration, and hyaline casts formation. In kidney tissue and urine, we revealed increased levels in markers of proliferation and injury. The explicit long-term consequence of photothrombosis-induced kidney ischemia was renal fibrosis. Thus, we establish a new low invasive experimental model of AKI, which provides a reproducible local ischemic injury lesion. We propose our model of photothrombosis-induced kidney ischemia as a useful approach for investigating AKI pathogenesis, studying the mechanisms of kidney regeneration, and development of therapy against AKI and CKD.

Calorie Restriction Provides Kidney Ischemic Tolerance in Senescence-Accelerated OXYS Rats.

Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR.

Age-Associated Loss in Renal Nestin-Positive Progenitor Cells.

The decrease in the number of resident progenitor cells with age was shown for several organs. Such a loss is associated with a decline in regenerative capacity and a greater vulnerability of organs to injury. However, experiments evaluating the number of progenitor cells in the kidney during aging have not been performed until recently. Our study tried to address the change in the number of renal progenitor cells with age. Experiments were carried out on young and old transgenic nestin-green fluorescent protein (GFP) reporter mice, since nestin is suggested to be one of the markers of progenitor cells. We found that nestin+ cells in kidney tissue were located in the putative niches of resident renal progenitor cells. Evaluation of the amount of nestin+ cells in the kidneys of different ages revealed a multifold decrease in the levels of nestin+ cells in old mice. In vitro experiments on primary cultures of renal tubular cells showed that all cells including nestin+ cells from old mice had a lower proliferation rate. Moreover, the resistance to damaging factors was reduced in cells obtained from old mice. Our data indicate the loss of resident progenitor cells in kidneys and a decrease in renal cells proliferative capacity with aging.

Dietary restriction modulates mitochondrial DNA damage and oxylipin profile in aged rats.

Age-related impairment of coordination of the processes of maintaining mitochondrial homeostasis is associated with a decrease in the functionality of cells and leads to degenerative processes. mtDNA can be a marker of oxidative stress and tissue degeneration. However, the mechanism of accumulation of age-related damage in mtDNA remains unclear. In the present study, we analyzed the accumulation of mtDNA damage in several organs of rats during aging and the possibility of reversing these alterations by dietary restriction (DR). We showed that mtDNA of brain compartments (with the exception of the cerebellum), along with kidney mtDNA, was the most susceptible to accumulation of age-related damage, whereas liver, testis, and lung were the least susceptible organs. DR prevented age-related accumulation of mtDNA damage in the cortex and led to its decrease in the lung and testis. Changes in mtDNA copy number and expression of genes involved in the regulation of mitochondrial biogenesis and mitophagy were also tissue-specific. There was a tendency for an age-related decrease in the copy number of mtDNA in the striatum and its increase in the kidney. DR promoted an increase in the amount of mtDNA in the cerebellum and hippocampus. mtDNA damage may be associated not only with the metabolic activity of organs, but also with the lipid composition and activity of processes associated with the isoprostanes pathway of lipid peroxidation. The comparison of polyunsaturated fatty acids and oxylipin profiles in old rats showed that DR decreased the synthesis of arachidonic acid and its metabolites synthesized by the cyclooxygenase, cytochrome P450 monooxygenases and lipoxygenase metabolic pathways.

Is the Mitochondrial Membrane Potential (∆Ψ) Correctly Assessed? Intracellular and Intramitochondrial Modifications of the ∆Ψ Probe, Rhodamine 123.

The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its role in bioenergetics since it takes part in other important intracellular processes, which leads to the mandatory requirement of the homeostasis of ∆Ψ. Conventionally, ∆Ψ in living cells is estimated by the fluorescence of probes such as rhodamine 123, tetramethylrodamine, etc. However, when assessing the fluorescence, the possibility of the intracellular/intramitochondrial modification of the rhodamine molecule is not taken into account. Such changes were revealed in this work, in which a comparison of normal (astrocytic) and tumor (glioma) cells was conducted. Fluorescent microscopy, flow cytometry, and mass spectrometry revealed significant modifications of rhodamine molecules developing over time, which were prevented by amiodarone apparently due to blocking the release of xenobiotics from the cell and their transformation with the participation of cytochrome P450. Obviously, an important role in these processes is played by the increased retention of rhodamines in tumor cells. Our data require careful evaluation of mitochondrial ∆Ψ potential based on the assessment of the fluorescence of the mitochondrial probe.

Gut Microbiota as a Source of Uremic Toxins.

Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as "uremic toxins". The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.

Isn't It Time for Establishing Mitochondrial Nomenclature Breaking Mitochondrial Paradigm?

In this work, we decided to initiate a discussion concerning heterogeneity of mitochondria, suggesting that it is time to build classification of mitochondria, like the one that exists for their progenitors, α-proteobacteria, proposing possible separation of mitochondrial strains and maybe species. We continue to adhere to the general line that mitochondria are friends and foes: on the one hand, they provide the cell and organism with the necessary energy and signaling molecules, and, on the other hand, participate in destruction of the cell and the organism. Current understanding that the activity of mitochondria is not only limited to energy production, but also that these alternative non-energetic functions are unique and irreplaceable in the cell, allowed us to speak about the strong subordination of the entire cellular metabolism to characteristic functional manifestations of mitochondria. Mitochondria are capable of producing not only ATP, but also iron-sulfur clusters, steroid hormones, heme, reactive oxygen and nitrogen species, participate in thermogenesis, regulate cell death, proliferation and differentiation, participate in detoxification, etc. They are a mandatory attribute of eukaryotic cells, and, so far, no eukaryotic cells performing a non-parasitic or non-symbiotic life style have been found that lack mitochondria. We believe that the structural-functional intracellular, intercellular, inter-organ, and interspecific diversity of mitochondria is large enough to provide grounds for creating a mitochondrial nomenclature. The arguments for this are given in this analytical work.

Neuroprotective Potential of Mild Uncoupling in Mitochondria. Pros and Cons.

There has been an explosion of interest in the use of uncouplers of oxidative phosphorylation in mitochondria in the treatment of several pathologies, including neurological ones. In this review, we analyzed all the mechanisms associated with mitochondrial uncoupling and the metabolic and signaling cascades triggered by uncouplers. We provide a full set of positive and negative effects that should be taken into account when using uncouplers in experiments and clinical practice.

Dietary Restriction for Kidney Protection: Decline in Nephroprotective Mechanisms During Aging.

Dietary restriction (DR) is believed to be one of the most promising approaches to extend life span of different animal species and to delay deleterious age-related physiological alterations and diseases. Among others, DR was shown to ameliorate acute kidney injury (AKI) and chronic kidney disease (CKD). However, to date, a comprehensive analysis of the mechanisms of the protective effect of DR specifically in kidney pathologies has not been carried out. The protective properties of DR are mediated by a range of signaling pathways associated with adaptation to reduced nutrient intake. The adaptation is accompanied by a number of metabolic changes, such as autophagy activation, metabolic shifts toward lipid utilization and ketone bodies production, improvement of mitochondria functioning, and decreased oxidative stress. However, some studies indicated that with age, the gain of DR-mediated positive remodeling gradually decreases. This may be an obstacle if we seek to translate the DR approach into a clinic for the treatment of kidney diseases as most patients with AKI and CKD are elderly. It is well known that aging is accompanied by impairments in a huge variety of organs and systems, such as hormonal regulation, stress sensing, autophagy and proteasomal activity, gene expression, and epigenome profile, increased damage to macromolecules and organelles including mitochondria. All these age-associated changes might be the reasons for the reduced protective potential of the DR during aging. We summarized the available mechanisms of DR-mediated nephroprotection and described ways to improve the effectiveness of this approach for an aged kidney.

Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats.

Dietary restriction (DR) is the strategy ameliorating the morbidity of various pathologies, including age-associated diseases. Acute kidney injury (AKI) remains a problem for the elderly with DR being a promising approach for diminishing its consequences. We evaluated the possible nephroprotective potential of short-term DR in young and old rats. DR in young rats resulted in pronounced beneficial effects normalizing lipid metabolism (triglycerides concentration, adiponectin level) activating autophagic-lysosomal system evaluated by LC3II/LC3I ratio, LAMP1, p62/SQSTM1 levels, and LysoTracker Green staining. DR had a remarkable recovering effect on mitochondrial structure and functions including regaining of mitochondrial membrane potential, the elevation of SIRT-3, PGC-1α, Bcl-XL levels and partial restoration of ultrastructure. The beneficial effects of DR resulted in the mitigation of oxidative stress including a decrease in levels of protein carbonylation and lipid peroxidation. Aging led to decreased activity of autophagy, elevated oxidative stress and impaired kidney regenerative capacity. Eventually, in old rats, even 8-week DR was not able to ameliorate AKI, but it caused some rejuvenating effects including elevation of mitochondrial membrane potential and Bcl-XL levels, as well as lowered severity of the oxidative stress. Thus, the age-associated decline of protective signaling demands extended DR to achieve nephroprotective potential in old animals.

Microbiome-Metabolome Signature of Acute Kidney Injury.

Intestinal microbiota play a considerable role in the host's organism, broadly affecting its organs and tissues. The kidney can also be the target of the microbiome and its metabolites (especially short-chain fatty acids), which can influence renal tissue, both by direct action and through modulation of the immune response. This impact is crucial, especially during kidney injury, because the modulation of inflammation or reparative processes could affect the severity of the resulting damage or recovery of kidney function. In this study, we compared the composition of rat gut microbiota with its outcome, in experimental acute ischemic kidney injury and named the bacterial taxa that play putatively negative or positive roles in the progression of ischemic kidney injury. We investigated the link between serum creatinine, urea, and a number of metabolites (acylcarnitines and amino acids), and the relative abundance of various bacterial taxa in rat feces. Our analysis revealed an increase in levels of 32 acylcarnitines in serum, after renal ischemia/reperfusion and correlation with creatinine and urea, while levels of three amino acids (tyrosine, tryptophan, and proline) had decreased. We detected associations between bacterial abundance and metabolite levels, using a compositionality-aware approach-Rothia and Staphylococcus levels were positively associated with creatinine and urea levels, respectively. Our findings indicate that the gut microbial community contains specific members whose presence might ameliorate or, on the contrary, aggravate ischemic kidney injury. These bacterial taxa could present perspective targets for therapeutical interventions in kidney pathologies, including acute kidney injury.