Histone lactylation, an indicator of lactate level and glycolysis, has intrinsic connections with cell metabolism that represents a novel epigenetic code affecting the fate of cells including carcinogenesis. Through delineating the relationship between histone lactylation and cancer hallmarks, we propose histone lactylation as a novel epigenetic code priming cells toward the malignant state, and advocate the importance of identifying novel therapeutic strategies or dual-targeting modalities against lactylation toward effective cancer control. This review underpins important yet less-studied area in histone lactylation, and sheds insights on its clinical impact as well as possible therapeutic tools targeting lactylation.

The human large intestinal microbiota thrives on dietary carbohydrates that are converted to a range of fermentation products. Short-chain fatty acids (acetate, propionate and butyrate) are the dominant fermentation acids that accumulate to high concentrations in the colon and they have health-promoting effects on the host. Although many gut microbes can also produce lactate, it usually does not accumulate in the healthy gut lumen. This appears largely to be due to the presence of a relatively small number of gut microbes that can utilise lactate and convert it to propionate, butyrate or acetate. There is increasing evidence that these microbes play important roles in maintaining a healthy gut environment. In this review, we will provide an overview of the different microbes involved in lactate metabolism within the gut microbiota, including biochemical pathways utilised and their underlying energetics, as well as regulation of the corresponding genes. We will further discuss the potential consequences of perturbation of the microbiota leading to lactate accumulation in the gut and associated disease states and how lactate-utilising bacteria may be employed to treat such diseases.

The prediction of prognosis is an important part of management in hepatitis B virus (HBV)-related decompensated cirrhosis patients with high long-term mortality. Lactate is a known predictor of outcome in critically ill patients. The aim of this study was to assess the prognostic value of lactate in HBV-related decompensated cirrhosis patients. We performed a single-centre, observational, retrospective study of 405 HBV-related decompensated cirrhosis patients. Individuals were evaluated within 24 h after admission and the primary outcome was evaluated at 6-months. Multivariable analyses were used to determine whether lactate was independently associated with the prognosis of HBV-related decompensated cirrhosis patients. The area under the ROC (AUROC) was calculated to assess the predictive accuracy compared with existing scores. Serum lactate level was significantly higher in non-surviving patients than in surviving patients. Multivariable analyses demonstrated that lactate was an independent risk factor of 6-months mortality (odds ratio: 2.076, P < 0.001). Receiver operating characteristic (ROC) curves were drawn to evaluate the discriminative ability of lactate for 6-months mortality (AUROC: 0.716, P < 0.001). Based on our patient cohort, the new scores (Model For End-Stage Liver Disease (MELD) + lactate score, Child–Pugh + lactate score) had good accuracy for predicting 6-months mortality (AUROC = 0.769, P < 0.001; AUROC = 0.766, P < 0.001). Additionally, the performance of the new scores was superior to those of existing scores (all P < 0.001). Serum lactate at admission may be useful for predicting 6-months mortality in HBV-related decompensated cirrhosis patients, and the predictive value of the MELD score and Child–Pugh score was improved by adjusting lactate. Serum lactate should be part of the rapid diagnosis and initiation of therapy to improve clinical outcome.

Introduction: Early Emergency Department (ED) identification of septic patients at risk of subsequent deterioration is necessary in order to optimize disposition. High-risk patients admitted directly from the ED to the ICU have better outcomes than those admitted to the floor first. Initial ED serum lactate level has been associated with 28-day mortality in admitted patients, but there is little evidence on its use in predicting short-term deterioration. Furthermore, it is unclear whether the addition of respiratory rate (RR) to lactate would create a stronger predictive model of deterioration than either alone. Methods: Prospective cohort study of ED patients (age ≥18) screened and treated for sepsis (defined as physician suspicion of infection and 2 or more of the SIRS criteria). Lactate and vital signs were obtained within 2 hours of ED arrival. Main outcome was deterioration (defined as any of the following: death; ICU admission >24 hours; Intubation; Vasoactive medications for >1 hour; or Non-invasive positive pressure ventilation for >1 hour) within 72 hours. Patients meeting an endpoint within 1 hour of arrival were excluded. Discharged patients were contacted at 72 hours to ensure that they had not met the endpoint or presented to another institution. Results: 985 patients presenting to either of two urban high-volume EDs were enrolled, of whom 84 (8.5%) met the primary outcome. Initial serum lactate ≥ 4.0 had a specificity of 97.4% (95% CI, 94.1-100%), but a sensitivity of 27.4% (95% CI, 17-8-36.9%) for predicting deterioration. Of patients with a lactate ≥ 4.0, 4 (8.7%) were discharged home, and did not reach an endpoint at 72 hours. Lactate <2.0 had a sensitivity of 95.5% (95% CI: 93.4-97.1%) and specificity of 84.5% (95% CI: 80.4-88.6%) for ruling out 72-hour deterioration. Of patients with a lactate <2.0, 224 (56.1%) were discharged home. Combining lactate with RR (AUC: 0.72, 95% CI: 0.66-0.79) did not yield better predictive capability than lactate alone (AUC: 0.70, 95% CI: 0.64-0.76). Conclusion: Initial ED lactate is predictive of deterioration within 72 hours in patients with sepsis. The combination of lactate and RR was not more predictive of deterioration than lactate alone. This suggests that serum lactate has a role in predicting deterioration in patients with sepsis, and has utility in determining disposition.

This study examined the effect of increasing BW ratio (BWR) between rider and horse, in the BWR range common for Icelandic horses (20% to 35%), on heart rate (HR), plasma lactate concentration (Lac), BWR at Lac 4 mmol/l (W4), breathing frequency (BF), rectal temperature (RT) and hematocrit (Hct) in Icelandic horses. In total, eight experienced school-horses were used in an incremental exercise test performed outdoors on an oval riding track and one rider rode all horses. The exercise test consisted of five phases (each 642 m) in tölt, a four-beat symmetrical gait, at a speed of 5.4±0.1 m/s (mean±SD), where BWR between rider (including saddle) and horse started at 20% (BWR20), was increased to 25% (BWR25), 30% (BWR30), and 35% (BWR35) and finally decreased to 20% (BWR20b). Between phases, the horses were stopped (~5.5 min) to add lead weights to specially adjusted saddle bags and a vest on the rider. Heart rate was measured during warm-up, the exercise test and after 5, 15 and 30 min of recovery and blood samples were taken and BF recorded at rest, and at end of each of these aforementioned occasions. Rectal temperature was measured at rest, at end of the exercise test and after a 30-min recovery period. Body size and body condition score (BCS) were registered and a clinical examination performed on the day before the test and for 2 days after. Heart rate and BF increased linearly (P<0.05) and Lac exponentially (P<0.05) with increasing BWR. The W4 was 22.7±4.3% (individual range 17.0% to 27.5%). There was a positive correlation between back BCS and W4 (r=0.75; P=0.032), but no other correlations between body measurements and W4 were found. Hematocrit was not affected by BWR (P>0.05), but negative correlations (P<0.05) existed between body size measurements and Hct. While HR, Hct and BF recovered to values at rest within 30 min, Lac and RT did not. All horses had no clinical remarks on palpation and at walk 1 and 2 days after the test. In conclusion, increasing BWR from 20% to 35% resulted in increased HR, Lac, RT and BF responses in the test group of experienced adult Icelandic riding horses. The horses mainly worked aerobically until BWR reached 22.7%, but considerable individual differences (17.0% to 27.5%) existed that were not linked to horse size, but to back BCS.

The objectives of this study were to assess the relationship between blood lactate variation measured at the plant, and pork quality variation on a large sample size and under commercial preslaughter handling conditions. A total of 600 pigs were randomly chosen on arrival at a commercial slaughter plant and blood samples taken from the ear vein at unloading (UN), after lairage (LA), in the restrainer (RE; before stunning) and at exsanguination (EX) were analysed for lactate content using a Lactate Scout Analyzer (LSA). In order to have a large range of measures, pigs were distributed into two groups; one kept in lairage overnight (G1) and the other for 2 to 3 h (G2) before slaughter. Meat quality was assessed in the Longissimus thoracis (LT), Semimembranosus (SM) and Adductor (AD) muscles by measuring the pH 30 min postmortem (pH1) and at 24 h postmortem (pHu), the colour and the drip loss. Blood lactate levels did not differ between G1 and G2 (P>0.05). A reduced muscle lactate and glucose contents (P=0.02 and P=0.004, respectively) resulting in a lower (P<0.001) glycolytic potential (GP) was observed in the LT muscle of G1 pigs when compared with G2 loins. In the LT muscle of G1 pigs, the lower GP resulted in an increased pHu (r=−0.67; P<0.001), decreased drip loss (r=0.57; P<0.001) and darker colour (r=0.50; P<0.001) compared with G2. In both G1 and G2 pigs, the lower GP was correlated to higher pHu value in the SM and AD muscles (r=−0.73; P<0.001). The greatest correlation was observed in G2 between blood lactate levels at LA and pHu value of the SM and AD muscles (r=0.46 and r=0.44, respectively; P<0.001 for both muscles). The second greatest correlation was found between blood lactate levels at EX and pH1 value in the SM muscle in both groups (r=−0.37 and r=−0.41, respectively; P<0.001 for both groups). Based on the results of this study, it appears that blood lactate levels, as measured by the LSA, reliably reflect the physiological response of pigs to perimortem stress and may help explain the variation in pork quality.

The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.

The assumption, that metabolites derived from the activity of the mammary gland epithelial cells reflect changes in milk secretion and its coagulation properties, was tested in dairy cows. The experiment included cows with uninfected udders and cows with one of the glands infected by different bacteria specie. Analysis were carried at the cow level (including all four glands), or at the gland level. High and significant correlations among the concentrations of lactose, glucose, glucose-6-posphate, milk related respiratory index (the ratio between the concentrations of citrate/lactate+malate in milk) and milk-derived glycolytic index (the ratio between glucose-6-phosphate and glucose in milk) and milk clotting parameters were found. The physiological basis for these relations and their ability to predict the deterioration in milk quality in subclinically infected glands and in glands previously clinically infected with Escherichia coli are discussed.

This study examined the response in terms of heart rate (HR), respiratory rate (RR), haematocrit (Htc), rectal temperature (RT), and some plasma variables in Icelandic horses of different sexes and ages performing the riding assessment in a breed evaluation field test (BEFT). The study was conducted in Iceland on 266 horses (180 mares and 86 stallions, divided into four age groups; 4, 5, 6 and ⩾7 years old). RT and RR were recorded and blood samples were taken before the warm-up and after the riding assessment. Horse HR, velocity and distance were recorded during the warm-up, the riding assessment and a 5-min recovery period. The distance covered in the BEFT was 2.9±0.4 km (range: 1.8 to 3.8 km, n=248), the duration was 9:37±1:22 min:s (range: 5:07 to 15:32 min:s, n=260) and the average speed was 17.8±1.4 km/h (range: 13.2 to 21.3 km/h, n=248). Average HR was 184±13 b.p.m. (range: 138 to 210 b.p.m., n=102) and peak HR 224±9 b.p.m. (range: 195 to 238 b.p.m., n=102), and 36% of the BEFT was performed at HR ⩾200 b.p.m. Post-exercise plasma lactate concentration (Lac) was 18.0±6.5 mmol/l (range: 2.1 to 34.4 mmol/l, n=266), and there was an increase in total plasma protein, plasma creatine kinase and aspartate amino transferase concentration, as well as RR, RT and Htc. Stallions covered a longer total distance (in the warm-up and BEFT) (P<0.05), at a faster speed during BEFT (P<0.001) than mares and had higher Htc and lower HR and post-exercise Lac values. There were few effects of age, but the 4- and 5-year-old horses had lower Htc than older horses and 4-year-old horses had higher post-exercise RR than older horses, although they were ridden for a shorter distance, shorter duration and at lower peak velocity (P<0.1). The results showed that the riding assessment in the BEFT is a high-intensity exercise. The results also showed that aerobic fitness was higher in stallions and that age had a limited effect on the physiological response. It is suggested that these results should be used as a guide for the development of training programmes and fitness tests in Icelandic horses that would improve both performance and welfare of the horse.

Fenugreek seed has been shown to affect the intestinal microbiota and immunological responses in animals. A feeding trial with male castrated piglets was performed over 28 d without or with the addition of 1·5 g fenugreek seeds/kg complete diet in ten and eleven piglets, weaned at 21 d. In the intestinal tract, pH, lactate and SCFA were measured as major bacterial metabolites. Immune cell phenotypes, phagocytic activity and lymphocyte proliferation after stimulation with pokeweed mitogen, concanavalin A and phytohaemagglutinin M were measured by flow cytometry. Health status and performance of the piglets were not affected by fenugreek. The pH in the caecum and colon were reduced compared with the control (P< 0·05). Higher concentrations of l-lactic acid were recorded in the small-intestinal digesta (average concentrations from the duodenum, jejunum and ileum; P< 0·05), while the concentrations of SCFA remained unchanged except an increase in n-butyric acid in colon contents (P< 0·05). The piglets fed the fenugreek diet had higher Lactobacillus and clostridium cluster I concentrations and lower Escherichia, Hafnia and Shigella concentrations in the small intestine. The addition of fenugreek increased the relative concentration of the γδ T-cell population (TCR1+CD8α−) in the blood with a simultaneous reduction of antigen-presenting cells (MHCII+CD5−) (P< 0·05). Proliferation rate and phagocytosis activity of monocytes were not affected by the additive. In conclusion, fenugreek seeds might be interesting as a feed ingredient for young piglets due to their effects on the intestinal microbiota and immunological variables. The impact on performance and animal health has to be further evaluated.