Role Of Lactic Acid Research Articles

Innovative Lactic Acid Production Techniques Driving Advances in Silage Fermentation

Lactic acid (LA) plays a crucial role in the silage process, which occurs through LA fermentation. Consequently, there is a strong correlation between lactic acid production and the efficiency of the silage. However, traditional methods face challenges like long fermentation times, low acid production, and unstable quality, limiting agricultural preservation. This paper aims to explore innovations in lactic acid production technologies and show how these technologies have driven the development of silage fermentation for agricultural conservation. First, the important role of LA in agricultural preservation and the limitations of traditional silage techniques are presented. Next, advancements in LA production methods are thoroughly examined, covering the selection of microbial strains and the substitution of fermentation substrates. Following this, new technologies for silage fermentation are explored, drawing from innovations in LA production. These include the selection of LA strains, optimization of fermentation conditions, and improvements in fermentation techniques. These innovations have proven effective in increasing LA production, improving feed quality, extending shelf life, and providing new solutions to enhance agricultural production and sustainability.

Biotechnological Strategies and Perspectives for Food Waste Treatment: The Role of Lactic Acid and Microbial Biomass

Biotechnological Strategies and Perspectives for Food Waste Treatment: The Role of Lactic Acid and Microbial Biomass

Enhanced hydrogen production performance via noble-metal-free amorphous NiZnSx-CS co-catalyst with novel gradient coating structure

In photocatalytic water splitting for hydrogen production, co-catalyst is a key factor in enhancing the efficiency of photocatalyst. Various inexpensive co-catalysts besides noble metal co-catalysts have been developed; however, the illumination of the relationship between the structure and performance remains a challenge. Here, we present a bimetallic sulfide co-catalyst denoted as NiZnSx-CS with amorphous and gradient coating structures to achieve highly efficient hydrogen production activity. Upon coupling the co-catalyst with CdS, the hydrogen production rate of CdS loaded with NiZnSx-CS reaches 38.0 mmol/g/h, 11.0, 40.0 and 161.0 times higher than that loaded with bulk NiZnSx, 1.0 %Pt and naked CdS, respectively. The co-catalyst with an amorphous and gradient coating structure shows large capacitance and thus facilitates efficient storage, transfer, and separation of photo-excited electrons of semiconductors, effectively reducing the over-potential of hydrogen production. The co-catalyst also has a large specific surface area and excellent hydrophilicity attributed to the abundant active sites and intimate contact with the reactant. Additionally, the coordination structure and chemical environment of NiZnSx-CS elucidated using X-ray absorption spectroscopy (XAS). The intermediates and the role of lactic acid and water on the surface of NiZnSx-CS after irradiation are determined by in situ Fourier transform infrared spectroscopy (in situ FT-IR). This work proposes a strategy to develop a highly efficient special structure co-catalyst with suitable capacitance, specific surface area and hydrophilicity.

The history context and future directions of lactic acid

Lactic acid, initially considered a neglected metabolic waste product, has gradually shown its irreplaceable value in the human body. Up to now, it has become a hot topic of current research. From its first time its discovery in milk to its becoming a product of cellular respiration and metabolism, lactic acid was viewed to be a useless product in metabolism and therefore resulted in the suspension of related research. Later, with the birth of the concept of lactate shuttle between cells, lactate once again showed a very important function in the energy field of physiological research, including the participation of whole-body energy metabolism and the regulation of the cancer microenvironment. However, after some time, the research on lactic acid seems to have stalled again in the role of lactic acid as a small molecule. Not until 2019, the discovery of acetylation of histone extended a new field of lactate research epigenetic modification. This review summarizes the research on various aspects of lactate and highlights the progress and application of lactate in histone modification.

Role of lactic acid and lactylation in nonalcoholic fatty liver disease

Role of lactic acid and lactylation in nonalcoholic fatty liver disease

Lactic Acid-Induced Colloidal Microrheology of Synovial Fluids.

The presence of colloidal scaffolds composed of proteins and hyaluronic acid engenders unique viscous and elastic properties to the synovial fluid (SF). While the elastic resistance of SF due to the presence of such nanoscale structures provides the load-bearing capacity, the viscous nature enables fluidity of the joints during the movements to minimize the wear and tear of the adjacent muscle, cartilage, or bone tissues. It is well-known that the hypoxic conditions at the bone joints often increase the lactic acid (LA) concentration due to the occurrence of excess anaerobic respiration during either hyperactivity or arthritic conditions. The present study uncovers that in such a scenario, beyond a critical loading of LA, the colloidal nanoscaffolds of SF break down to precipitate higher molecular weight (MW) proteins and hyaluronic acid (HA). Subsequently, the viscosity and elasticity of SF reduce drastically to manifest a fluid that has reduced load bearing and wear and tear resistance capacity. Interestingly, the study also suggests that a heathy SF is a viscoelastic fluid with a mild Hookean elasticity and non-Newtonian fluidity, which eventually transforms into a viscous watery liquid in the presence of a higher loading of LA. We employ this knowledge to biosynthesize an artificial SF that emulates the characteristics of the real one. Remarkably, the spatiotemporal microscopic images uncover that even for the artificial SF, a dynamic cross-linking of the high MW proteins and HA takes place before precipitating out of the same from the artificial SF matrix, emulating the real one. Control experiments suggest that this phenomenon is absent in the case when LA is mixed with either pure HA or proteins. The experiments unfold the specific role of LA in the destruction of colloidal nanoscaffolds of synovia, which is an extremely important requirement for the biosynthesis and translation of artificial synovial fluid.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

Lactic acid enhances vaginal epithelial barrier integrity and ameliorates inflammatory effects of dysbiotic short chain fatty acids and HIV-1

The vaginal microenvironment is key in mediating susceptibility to sexually transmitted infections. A polymicrobial environment with reduced Lactobacilllus spp. is characteristic of vaginal dysbiosis, associated with increased production of several short chain fatty acids (SCFAs), vaginal inflammation and an increased risk of HIV-1 acquisition. In contrast, a eubiotic vaginal microbiome (VMB), dominated by Lactobacillus spp. correlates with increased production of lactic acid (LA), an acidic milieu and protection against HIV-1. Vaginal metabolites, specifically LA and SCFAs including butyric, succinic and acetic acids are associated with modulation of HIV-1 risk. We assessed the impact of combined and individual SCFAs and LA on vaginal epithelial cells (VK2) grown in air–liquid interface cultures. Treatment of VK2 cells with eubiotic SCFA + LA mixture showed increased epithelial barrier integrity, reduced FITC dextran leakage and enhanced expression of cell–cell adhesion proteins. Treatment with dysbiotic SCFA + LA mixture diminished epithelial barrier integrity, increased NFκB activation and inflammatory mediators: TNF-α, IL-6, IL-8 and RANTES. LA was found to be the primary contributor of the beneficial effects. Eubiotic SCFA + LA mixture ameliorated HIV-1 mediated barrier disruption and HIV-1 leakage, whereas dysbiotic SCFA + LA treatment exacerbated HIV-1 effects. These findings indicate a key role for LA in future prophylactic strategies.

Efficient co-production of xylo-oligosaccharides and probiotics from corncob by combined lactic acid pretreatment and two-step enzymatic hydrolysis

Lactic acid (LA) is efficient in xylo-oligosaccharides (XOS) production from poplar. However, the role of LA in XOS production from corncob has not been carefully elucidated, and the co-production of probiotics of Bacillus subtilis from corncob residue has not been reported. In this study, LA pretreatment was combined with enzymatic hydrolysis to produce XOS and monosaccharides from corncob. An XOS yield of 69.9% was obtained from corncob by combining 2% LA pretreatment and xylanase hydrolysis. Yields of 95.6% glucose and 54.0% xylose were obtained from corncob residue via cellulase, and the resulting cellulase hydrolysate was used to culture Bacillus subtilis YS01. The resulting viable count of the strain was 6.4×108 CFU/mL, and the glucose and xylose utilization were 99.0% and 89.8%, respectively. This study demonstrated a green, efficient, and mild process for producing XOS and probiotics from corncob by combining LA pretreatment and enzymatic hydrolysis.

The use of a lactic acid gel in the treatment and prevention of bacterial vaginosis and urinary tract infections as a challenge to antibacterial therapy. A literature review

Bacterial vaginosis and urinary tract infections are common conditions that lead to a decrease in the quality of life and significant economic costs. The review provides up-to-date information on the role of lactic acid in the microbiota of the vagina and urinary tract, as well as on the use of a lactic acid gel in these conditions. Bacterial vaginosis is associated with an increased risk of urinary tract infections. Antibacterial therapy demonstrates statistically significant results in treating exacerbation, but not preventing further relapses, which is due to the possible high ability of bacteria to form biofilms. Lactic acid, unlike hydrogen peroxide, is involved in maintaining the vaginal microbiota and enhancing its protective function against sexually transmitted infections, and indirectly affects the urinary microbiota. This may allow the use of lactic acid for the treatment and prevention of relapses in both bacterial vaginosis and urinary tract infections.

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization.

Simple SummaryFor a long-time lactic acid has been considered as a toxic end-product of metabolism that cause different adverse effects. However, in recent decades a plenty of studies has refuted this suggestion and revealed many functions of lactate in living organisms. Lactic acid may be considered as one of the most ancient metabolites with signaling function and high regulatory activity. Lactate regulates key metabolic processes such as proteins expression, cells’ differentiation, inflammatory response, as well as provides stemness and unlimited cell growth, which is used by malignant tumors for their growth. Although lactatemia, observed in many cancer diseases, is possibly associated with the activation of ancient evolutionary defense mechanisms, aimed at combating metabolic disorders, and which tumors began to use for their own purposes – the acquisition of stem properties, rapid proliferation, and metastasis. In our review we aimed to summarize the accumulated knowledge about the functions of lactate in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate’s role in the malignant transformation becomes more relevant in the light of the “atavistic theory of carcinogenesis,” which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

The Role of Lactic Acid in the Management of Bacterial Vaginosis: A Systematic Literature Review

Bacterial vaginosis (BV) is a common infection characterized by an imbalance in the vaginal microbiome. Alongside the extensive research for effective therapies, treatment recommendations for symptomatic BV with antibiotics have been developed and are currently available. However, the recurrence of BV remains a considerable challenge given that about 60% of women experience BV relapse within six months after initial treatment. In addition, clear guidelines on the treatment of asymptomatic BV during pregnancy or for BV mixed infections are still missing. Lactic acid has been put forward as a potential treatment or for prophylaxis of BV due to its ability to restore the imbalance of the vaginal microbiota and to promote the disruption of vaginal pathogenic bacterial biofilms, which might trigger BV recurrence. This review evaluates the clinical evidence regarding the efficacy and prophylactic potential of lactic acid in BV through a systematic literature search. In addition, a treatment regimen consisting of lactic acid as a standalone treatment or in combination with current recommended therapies for practice is suggested based on these findings and stratified according to BV severity, pregnancy status, and coincidence with vulvovaginal candidosis (VVC) or trichomoniasis.

A novel formation pathway of Nε-(carboxyethyl)lysine from lactic acid during high temperature exposure in wheat sourdough bread and chemical model

Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) have been the most extensively studied advanced glycation end-products (AGEs) in foods. Their formation mechanism, especially the latter, has not been clearly delineated in fermented food. In this work, the relative contents of CEL and CML were evaluated in a sourdough-bread and a silica solid chemical model. Lactic acid (LA) content in the sourdough increased with fermentation time that was accompanied by an increase in CEL, but not CML content in the bread. The role of LA as a precursor for CEL was supported by a positive significant correlation between LA and CEL contents, and further analysis using isotope-labeled LA (LA-13C3) revealed that the three carbon atoms of LA were incorporated into CEL. These findings for the first time indicate LA may function as a precursor to promote CEL formation in sourdough bread that merits further investigation.

The Role of Lactic Acid on Wound Healing, Cell Growth, Cell Cycle Kinetics, and Gene Expression of Cultured Junctional Epithelium Cells in the Pathophysiology of Periodontal Disease.

Lactic acid (LA) is short-chain fatty acid, such as butyric acid and propionic acid, that is produced as a metabolite of lactic acid bacteria, including periodontopathic bacteria. These short-chain fatty acids have positive effects on human health but can also have negative effects, such as the promotion of periodontal disease (PD), which is caused by periodontal pathogens present in the gingival sulcus. PD is characterized by apical migration of junctional epithelium, deepening of pockets, and alveolar bone loss. Thus, the junctional epithelial cells that form the bottom of the gingival sulcus are extremely important in investigating the pathophysiology of PD. The aim of this study was to investigate the effect of LA on wound healing, cell growth, cell cycle kinetics, and gene expression of cultured junctional epithelium cells. The results showed that stimulation with 10 mM LA slowed wound healing of the junctional epithelial cell layer and arrested the cell cycle in the G0/G1 (early cell cycle) phase, thereby inhibiting cell growth. However, cell destruction was not observed. LA also enhanced mRNA expression of integrin α5, interleukin (IL)-6, IL-8, intercellular adhesion molecule-1, and receptor activator of nuclear factor kappa-B ligand. The results of this study suggest that stimulation of junctional epithelial cells with high concentrations of LA could exacerbate PD, similarly to butyric acid and propionic acid.

A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation

Research questionIs the blastocyst's idiosyncratic metabolic production of lactate, and creation of a specialized microenvironment at the implatation site, an important mediator of maternal–fetal signalling to promote endometrial receptivity and implantation? DesignHormonally primed ECC-1 and Ishikawa cells were used to assess functional changes to the endometrial epithelium after exposure to lactic acid (LA), LA with neutralized pH (nLA) or acidic pH (pHL). Tight junction integrity (transepithelial resistance [TER]), cellular proliferation or changes to gene expression by RT-PCR were analysed. The effect of LA on Endometrial stromal cells decidualization and migratory capacity, and HUVEC endothelial tube formation and angiogenesis, were also assessed. ResultsTreatment of ECC-1 cells with 2.5 mM (P = 0.0037), 5 mM (P = 0.0044), 7.5 mM and 10 mM (P = 0.003) (P = 0.0021) LA significantly decreased the rate of cellular proliferation while TER was decreased with exposure to 2.5 mM LA (P = 0.024), 5 mM LA (P = 0.021) and 7.5 mM LA (P = 0.033). Exposure to nLA or pHL had no effect on proliferation or TER. Upregulation of GLUT4 (P = 0.002), GPR81 (P = 0.048), VEGF, SNAI1 (both P < 0.001) and RELA (P = 0.023) mRNA expression was observed after exposure of Ishikawa cells to combined LA plus pHL. Lactic acid increased the migratory capacity of decidualized stromal cells (P = 0.047) without changing the extent of decidualization. HUVEC tube formation was significantly increased by 5 mM LA exposure (P = 0.009). ConclusionsThe identification of LA as an important mediator in the maternal–fetal dialogue underpinning implantation is supported. Further examination of the role of LA within the infertile or compromised endometrium could improve natural and assisted pregnancy success and needs further investigation.

Beyond the Lactate Paradox: How Lactate and Acidity Impact T Cell Therapies against Cancer.

T cell therapies, including CAR T cells, have proven more effective in hematologic malignancies than solid tumors, where the local metabolic environment is distinctly immunosuppressive. In particular, the acidic and hypoxic features of the tumor microenvironment (TME) present a unique challenge for T cells. Local metabolism is an important consideration for activated T cells as they undergo bursts of migration, proliferation and differentiation in hostile soil. Tumor cells and activated T cells both produce lactic acid at high rates. The role of lactic acid in T cell biology is complex, as lactate is an often-neglected carbon source that can fuel TCA anaplerosis. Circulating lactate is also an important means to regulate redox balance. In hypoxic tumors, lactate is immune-suppressive. Here, we discuss how intrinsic- (T cells) as well as extrinsic (tumor cells and micro-environmental)-derived metabolic factors, including lactate, suppress the ability of antigen-specific T cells to eradicate tumors. Finally, we introduce recent discoveries that target the TME in order to potentiate T cell-based therapies against cancer.

Role of Lactic Acid as Predictor of Mortality in Patients with Acute Myocardial Infarction

The hypoxic-ischemic condition causes tissue metabolic abnormalities and organ dysfunction, characterized byelevated blood lactic acid levels. It is suspected that increased lactic acid in Acute Myocardial Infarction (AMI) patients couldincrease mortality risk. This study aimed to determine whether increased lactic acid levels could be used as a predictor ofmortality in AMI patients. The analytical observational-cohort study was performed on AMI patients who were admitted toDr. Saiful Anwar Malang Hospital from January 2018 to December 2019. Research subjects were divided into two groups, thegroup of deceased and living AMI patients, who were tested for lactic acid, troponin-I, CKMB, and creatinine levels atadmission. Diabetes mellitus and septic patients were excluded. For analysis of lactic acid as a predictor of mortality, ROCcurve analysis and odds ratio were used. There found that lactic acid levels in the deceased AMI patients group were highercompared to that of the living AMI patients (p &lt; 0.05). The sensitivity and specificity values of lactic acid as a predictor ofmortality in AMI patients at a cut-off of 3.5 mmol/L were 66.7% and 80%, respectively. Odds ratio analysis showed that AMIpatients with lactic acid levels more than 3.5 mmol/L had 8 times greater mortality risk than those whose level less than 3.5mmol/L. It was concluded that lactic acid level can be used as an indicator to predict the mortality of AMI patients.

Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer

BackgroundTo investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors.MethodsThe BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts.ResultsLA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate.ConclusionLA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC.DasE7LVW6tcKsMdapJmhMFVideo

Comparison of the antifungal effect of undissociated lactic and acetic acid in sourdough bread and in chemically acidified wheat bread

Sourdough is a very interesting natural preservation system to prolong mould free shelf-life of bread. Numerous studies have reported that the antifungal activity of sourdough is mainly correlated with the presence of lactic (LA) and acetic acid (AA), but very few information is available on the effect of undissociated acid concentrations in the aqueous phase of bread (CHA; mmole/L). This study was conducted to provide additional information about the mode of action of the acids in sourdough bread, enabling a better shelf-life prediction. This study was divided into two parts. In part 1, three industrial biological sourdoughs were characterized (dough yield, pH, aw, fermentation quotient, microbiota). During 7 weeks, a shelf-life test with natural flora was conducted with daily checks of visible mould growth (21 °C). In part 2, the effect of the acids present in the antifungal active sourdough breads was validated in chemically acidified wheat breads. Complete growth inhibition was observed in full-baked sourdough bread (30 g/100 g dough) containing Lactobacillus sanfranciscensis and Saccharomyces cerevisiae as dominant sourdough micro-organisms, whereas in control bread the shelf-life was limited to 4.4–9.2 days. These full-baked sourdough breads contained 36 mmole undissociated LA/L and 220 mmole undissociated AA/L. The data were used to make General Linear Regression models for shelf-life prediction and resulted in a fit of R2 = 0.79 when expressing the shelf-life in function of CHA,LA and CHA,AA. In acidified breads, the role of lactic acid was not significant and only impacted shelf-life indirectly through acidification. No difference between antifungal activity of sourdough breads and chemically acidified bread with comparable CHA,AA concentrations was observed. Shelf-life increased when 150–200 mmole undissociated AA/L aqueous phase in bread was present. To conclude, this study showed the importance of the undissociated acid fraction of acetic acid in relation to bread shelf-life, together with bread pH and moisture content.

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota.

Non-optimal vaginal microbiota, as observed in bacterial vaginosis (BV), is typically characterized by a depletion of beneficial lactobacilli and an abundance of numerous anaerobes. These non-optimal conditions are associated with subclinical cervicovaginal inflammation and an increased risk of HIV infection compared to women colonized with optimal vaginal microbiota dominated by lactobacilli. Lactic acid (LA) is a major organic acid metabolite produced by vaginal lactobacilli that elicits anti-inflammatory effects from cervicovaginal epithelial cells and is dramatically depleted during BV. However, it is unclear if LA retains its anti-inflammatory activity in the presence of vaginal microbiota metabolites comprising short chain fatty acids (SCFAs) and succinic acid, which are also produced by an optimal vaginal microbiota. Furthermore, the immunomodulatory effect of SCFAs and succinic acid on cervicovaginal epithelial cells at higher concentrations present during BV is unknown. Here we report that in the presence of physiologically relevant concentrations of SCFAs and succinic acid at pH 3.9 (as found in women with lactobacillus-dominated microbiota) LA induced an anti-inflammatory state in cervicovaginal epithelial cells and inhibited inflammation elicited by the toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid and Pam3CSK4. When cervicovaginal epithelial cells were treated with a vaginal microbiota metabolite mixture representative of BV, containing a lower concentration of LA but higher concentrations of SCFA/succinic acid at pH 7, no anti-inflammatory was observed. Rather, the vaginal microbiota metabolite mixture representative of BV dysregulated the immune response of cervicovaginal epithelial cells during prolonged and sustained treatments. This was evidenced by increased basal and TLR-induced production of pro-inflammatory cytokines including tumor necrosis factor-α, but decreased basal production of chemokines including RANTES and IP-10. Further characterization of individual components of the BV vaginal microbiota mixture suggested that acetic acid is an important vaginal microbiota metabolite capable of eliciting diverse immunomodulatory effects on a range of cervicovaginal epithelial cell targets. These findings indicate that elevated levels of SCFAs are a potential source of cervicovaginal inflammation in women experiencing BV, and support the unique anti-inflammatory properties of LA on cervicovaginal epithelial cells as well as a role for LA or LA-producing lactobacilli to reverse genital inflammation associated with increased HIV risk.