Effect of electron acceptors on product selectivity and carbon flux in carbon chain elongation with Megasphaera hexanoica.

Megasphaera hexanoica is a bacterial strain following the reverse ß-oxidation pathway to synthesize caproate (CA) using lactate (LA) as an electron donor (ED) and acetate (AA) or butyrate (BA) as electron acceptors (EA). Differences in the type and concentration of EA lead to distinctions in product distribution and energy bifurcation of carbon fluxes in ED pathways, thereby affecting CA production. In this study, the effect of various ratios of AA, BA, and AA+BA as EA on carbon flux and CA specific titer during the carbon chain elongation in M. hexanoica was explored. The results indicated that the maximum levels of CA were 18.81 mM and 31.48 mM when the molar ratios of LA/AA and LA/BA were 10:1 and 3:1, respectively. Meanwhile, when AA and BA were used as combined EA (LA, AA, and BA molar amounts of 100, 23, and 77 mM), a maximum CA production of 39.45 mM was obtained. Further analysis revealed that the combined EA exhibited a CA production carbon flux of 49 % (4.3 % and 19.5 % higher compared to AA or BA, respectively) and a CA production specific titer of 45.24 mol (80.89 % and 58.51 % higher compared to AA or BA, respectively), indicating that the effective carbon utilization rate and CA production efficiency were greatly improved. Finally, a scaled-up experiment was conducted in a 1.2 L (working volume) automated bioreactor, implying high biomass (optical density at 600 nm or OD600 = 1.809) and a slight decrease in CA production (28.45 mM). A decrease in H2 production (4.11 g/m3) and an increase in CO2 production (0.632 g/m3) demonstrated the appropriate metabolic adaptation of M. hexanoica to environmental changes such as stirring shear.

Lactate cross-feeding between Bifidobacterium species and Megasphaera indica contributes to butyrate formation in the human colonic environment.

Butyrate, a physiologically active molecule, can be synthesized through metabolic interactions among colonic microorganisms. Previously, in a fermenting trial of human fecal microbiota, we observed that the butyrogenic effect positively correlated with the increasing Bifidobacterium population and an unidentified Megasphaera species. Therefore, we hypothesized that a cross-feeding phenomenon exists between Bifidobacterium and Megasphaera, where Megasphaera is the butyrate producer, and its growth relies on the metabolites generated by Bifidobacterium. To validate this hypothesis, three bacterial species (B. longum, B. pseudocatenulatum, and M. indica) were isolated from fecal cultures fermenting hydrolyzed xylan; pairwise cocultures were conducted between the Bifidobacterium and M. indica isolates; the microbial interactions were determined based on bacterial genome information, cell growth, substrate consumption, metabolite quantification, and metatranscriptomics. The results indicated that two Bifidobacterium isolates contained distinct gene clusters for xylan utilization and expressed varying substrate preferences. In contrast, M. indica alone scarcely grew on the xylose-based substrates. The growth of M. indica was significantly elevated by coculturing it with bifidobacteria, while the two Bifidobacterium species responded differently in the kinetics of cell growth and substrate consumption. Coculturing led to the depletion of lactate and increased the formation of butyrate. An RNA-seq analysis further revealed the upregulation of M. indica genes involved in the lactate utilization and butyrate formation pathways. We concluded that lactate generated by Bifidobacterium through catabolizing xylose fueled the growth of M. indica and triggered the synthesis of butyrate. Our findings demonstrated a novel cross-feeding mechanism to generate butyrate in the human colon.IMPORTANCEButyrate is an important short-chain fatty acid that is produced in the human colon through microbial fermentation. Although many butyrate-producing bacteria exhibit a limited capacity to degrade nondigestible food materials, butyrate can be formed through cross-feeding microbial metabolites, such as acetate or lactate. Previously, the literature has explicated the butyrate-forming links between Bifidobacterium and Faecalibacterium prausnitzii and between Bifidobacterium and Eubacterium rectale. In this study, we provided an alternative butyrate synthetic pathway through the interaction between Bifidobacterium and Megasphaera indica. M. indica is a species named in 2014 and is indigenous to the human intestinal tract. Scientific studies explaining the function of M. indica in the human colon are still limited. Our results show that M. indica proliferated based on the lactate generated by bifidobacteria and produced butyrate as its end metabolic product. The pathways identified here may contribute to understanding butyrate formation in the gut microbiota.

Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas.

Human tumors harbor a plethora of microbiota. It has been shown that the composition and diversity of intratumor microbiome are significantly associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC). However, the association in Chinese patients as well as the effect of different microorganisms on inhibiting tumor growth are unclear. In this study, we collected tumor samples resected from long-term and short-term PDAC survivors and performed 16S rRNA amplicon sequencing. We found that the microbiome in samples with different survival time were significantly different, and the differential bacterial composition was associated with the metabolic pathways in the tumor microenvironment. Furthermore, administration of Megasphaera, one of the differential bacteria, induced a better tumor growth inhibition effect when combined with the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1) treatment in mice bearing 4T1 tumor. These results indicate that specific intratumor microbiome can enhance the anti-tumor effect in the host, laying a foundation for further clarifying the underlying detailed mechanism.

Chain elongation process for caproate production using lactate as electron donor in Megasphaera hexanoica.

Megasphaera hexnaoica is anaerobic bacteria who has well running reverse ß-oxidation pathway. In previous study, the strain showed excellent production of medium chain carboxylic acids (MCCAs) using fructose as electron donor. In this study, chain elongation process study using lactate instead of fructose was conducted in M. hexnaoica fermentation. It was found that M. hexanoica can use lactate as electron donor in chain elongation process. 8.9 g/L caproate production was achieved in fermentation using lactate as sole electron donor. Compare to fructose condition, lactate as electron donor showed more than 3 times higher specific titer and specific productivity. In addition, when fructose and lactate were used as electron donor simultaneously, further improvement of MCCAs production was observed to achieve maximum caproate productivity of 20.9 g/L/day. Utilization of lactate as electron donor in M. hexanoica showed potential opportunity in chain elongation process.

Vaginal and Extra-Vaginal Bacterial Colonization and Risk for Incident Bacterial Vaginosis in a Population of Women Who Have Sex With Men.

BACKGROUND: Bacterial vaginosis (BV) is a common cause of vaginal discharge and associated with vaginal acquisition of BV-associated bacteria (BVAB). METHODS: We used quantitative polymerase chain reaction assays to determine whether presence or concentrations of BVAB in the mouth, anus, vagina, or labia before BV predict risk of incident BV in 72 women who have sex with men. RESULTS: Baseline vaginal and extra-vaginal colonization with Gardnerella spp, Megasphaera spp, Sneathia spp, BVAB-2, Dialister sp type 2, and other BVAB was more common among subjects with incident BV. CONCLUSIONS: Prior colonization with BVAB is a consistent risk for BV.

Unique roles of vaginal Megasphaera phylotypes in reproductive health.

The composition of the human vaginal microbiome has been extensively studied and is known to influence reproductive health. However, the functional roles of individual taxa and their contributions to negative health outcomes have yet to be well characterized. Here, we examine two vaginal bacterial taxa grouped within the genus Megasphaera that have been previously associated with bacterial vaginosis (BV) and pregnancy complications. Phylogenetic analyses support the classification of these taxa as two distinct species. These two phylotypes, Megasphaera phylotype 1 (MP1) and Megasphaera phylotype 2 (MP2), differ in genomic structure and metabolic potential, suggestive of differential roles within the vaginal environment. Further, these vaginal taxa show evidence of genome reduction and changes in DNA base composition, which may be common features of host dependence and/or adaptation to the vaginal environment. In a cohort of 3870 women, we observed that MP1 has a stronger positive association with bacterial vaginosis whereas MP2 was positively associated with trichomoniasis. MP1, in contrast to MP2 and other common BV-associated organisms, was not significantly excluded in pregnancy. In a cohort of 52 pregnant women, MP1 was both present and transcriptionally active in 75.4 % of vaginal samples. Conversely, MP2 was largely absent in the pregnant cohort. This study provides insight into the evolutionary history, genomic potential and predicted functional role of two clinically relevant vaginal microbial taxa.

A specific structure and high richness characterize intestinal microbiota of HIV-exposed seronegative individuals.

Intestinal microbiota facilitates food breakdown for energy metabolism and influences the immune response, maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression or if it could modulate the risk of acquiring the HIV infection. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha (p = 0.040) and beta diversity (p = 0.006) compared to HC, but no differences were found compared to HIV+. A lower Treg percentage was observed in HESN (1.77%) than HC (2.98%) and HIV+ (4.02%), with enrichment of the genus Butyrivibrio (p = 0.029) being characteristic of this profile. Moreover, we found that Megasphaera (p = 0.017) and Victivallis (p = 0.0029) also are enriched in the microbiota composition in HESN compared to HC and HIV+ subjects. Interestingly, an increase in Succinivibrio and Prevotella, and a reduction in Bacteroides genus, which is typical of HIV-infected individuals, were observed in both HESN and HIV+, compared to HC. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.

Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer.

Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy.

Megasphaera in the Stool Microbiota Is Negatively Associated With Diarrheal Cryptosporidiosis.

BACKGROUND: The protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (ie, nondiarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during a Cryptosporidium infection. METHODS: To characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillance Cryptosporidium-positive fecal samples from 72 infants was evaluated using 16S ribosomal RNA gene sequencing. Additionally, the microbiome composition prior to infection was examined to test whether a preexisting microbiome profile could influence the Cryptosporidium infection phenotype. RESULTS: Fecal microbiome composition was associated with diarrheal symptoms at 2 timepoints. Megasphaera was significantly less abundant in diarrheal samples compared with subclinical samples at the time of Cryptosporidium detection (log2 [fold change] = -4.3; P = 10-10) and prior to infection (log2 [fold change] = -2.0; P = 10-4); this assigned sequence variant was detected in 8 children who had diarrhea and 30 children without diarrhea. Random forest classification also identified Megasphaera abundance in the pre- and postexposure microbiota as predictive of a subclinical infection. CONCLUSIONS: Microbiome composition broadly, and specifically low Megasphaera abundance, was associated with diarrheal symptoms prior to and at the time of Cryptosporidium detection. This observation suggests that the gut microenvironment may play a role in determining the severity of a Cryptosporidium infection. Clinical Trials Registration. NCT02764918.

Association Between Vaginal Bacterial Microbiota and Vaginal Yeast Colonization.

BACKGROUND: Vaginal yeast is frequently found with Lactobacillus-dominant microbiota. The relationship between vaginal yeast and other bacteria has not been well characterized. METHODS: These analyses utilized data from the Preventing Vaginal Infections trial. Relative abundance of vaginal bacteria from 16S ribosomal ribonucleic acid gene amplicon sequencing and quantities of 10 vaginal bacteria using taxon-directed polymerase chain reaction assays were compared at visits with and without detection of yeast on microscopy, culture, or both. RESULTS: Higher relative abundances of Megasphaera species type 1 (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.52-0.95), Megasphaera species type 2 (RR, 0.81; 95% CI, 0.67-0.98), and Mageeibacillus indolicus (RR, 0.46; 95% CI, 0.25-0.83) were associated with lower risk of detecting yeast. In contrast, higher relative abundances of Bifidobacterium bifidum, Aerococcus christensenii, Lactobacillus mucosae, Streptococcus equinus/infantarius/lutentiensis, Prevotella bivia, Dialister propionicifaciens, and Lactobacillus crispatus/helveticus were associated with yeast detection. Taxon-directed assays confirmed that increasing quantities of both Megasphaera species and M indolicus were associated with lower risk of detecting yeast, whereas increasing quantities of L crispatus were associated with higher risk of detecting yeast. CONCLUSIONS: Despite an analysis that examined associations between multiple vaginal bacteria and the presence of yeast, only a small number of vaginal bacteria were strongly and significantly associated with the presence or absence of yeast.

Pectinatus spp. - Unpleasant and recurrent brewing spoilage bacteria.

Traditionally, beer has been recognised as a beverage with high microbiological stability because of the hostile growth environment posed by beer and increasing attention being paid to brewery hygiene. However, the microbiological risk has increased in recent years because of technological advances toward reducing oxygen in beers, besides the increase in novel beer styles production, such as non-pasteurised, flash pasteurised, cold sterilised, mid-strength, and alcoholic-free beer, that are more prone to spoilage bacteria. Moreover, using innovative beer ingredients like fruits and vegetables is an added cause of microbial spoilage. To maintain quality and good brand image, beer spoilage microorganisms are a critical concern for breweries worldwide. Pectinatus and Megasphaera are Gram-negative bacteria mostly found in improper brewing environments, leading to consumer complaints and financial losses. Because of the lack of compiled scientific knowledge on Pectinatus spoilage ability, this review provides a comprehensive overview of the occurrence, survival mechanisms, and the factors affecting beer spoilage Pectinatus species in the brewing process.

Calcium salts of long-chain fatty acids from linseed oil decrease methane production by altering the rumen microbiome in vitro.

Calcium salts of long-chain fatty acids (CSFA) from linseed oil have the potential to reduce methane (CH4) production from ruminants; however, there is little information on the effect of supplementary CSFA on rumen microbiome as well as CH4 production. The aim of the present study was to evaluate the effects of supplementary CSFA on ruminal fermentation, digestibility, CH4 production, and rumen microbiome in vitro. We compared five treatments: three CSFA concentrations-0% (CON), 2.25% (FAL) and 4.50% (FAH) on a dry matter (DM) basis-15 mM of fumarate (FUM), and 20 mg/kg DM of monensin (MON). The results showed that the proportions of propionate in FAL, FAH, FUM, and MON were increased, compared with CON (P < 0.05). Although DM and neutral detergent fiber expressed exclusive of residual ash (NDFom) digestibility decreased in FAL and FAH compared to those in CON (P < 0.05), DM digestibility-adjusted CH4 production in FAL and FAH was reduced by 38.2% and 63.0%, respectively, compared with that in CON (P < 0.05). The genera Ruminobacter, Succinivibrio, Succiniclasticum, Streptococcus, Selenomonas.1, and Megasphaera, which are related to propionate production, were increased (P < 0.05), while Methanobrevibacter and protozoa counts, which are associated with CH4 production, were decreased in FAH, compared with CON (P < 0.05). The results suggested that the inclusion of CSFA significantly changed the rumen microbiome, leading to the acceleration of propionate production and the reduction of CH4 production. In conclusion, although further in vivo study is needed to evaluate the reduction effect on rumen CH4 production, CSFA may be a promising candidate for reduction of CH4 emission from ruminants.

Exploring the Maternal and Infant Oral Microbiomes: A Pilot Study.

Setting the stage for good oral health early in life is critical to long-term oral and overall health. This exploratory study aimed to characterize and compare maternal and newborn oral microbiota among mother-infant pairs. Oral samples were collected from 34 pregnant African American women and their infants at 1 to 3 months of age. Extracted 16SrRNA genes were matched to the Human Oral Microbiome Database. Alpha and beta diversity differed significantly between overall maternal and infant microbiomes. Maternal or infant alpha diversity, however, was not differentiated by maternal gingival status. Several demographic and behavioral variables were associated with, but not predictive of, maternal oral microbiome alpha diversity. There was no association, however, among birth mode, feeding mode, and the infant oral microbiome. Megasphaera micronuciformis was the only periodontal pathogen detected among the infants. Notably, maternal gingival status was not associated with the presence/absence of most periodontal pathogens. This study provides an initial description of the maternal and infant oral microbiomes, laying the groundwork for future studies. The perinatal period presents an important opportunity where perinatal nurses and providers can provide oral assessment, education, and referral to quality dental care.

Activation of butyrate-producing bacteria as well as bifidobacteria in the cat intestinal microbiota by the administration of 1-kestose, the smallest component of fructo-oligosaccharide.

1-kestose is a structural component of fructo-oligosaccharides and is composed of 2 fructose residues bound to sucrose through ß2-1 bonds. In the present study, the influence of the ingestion of 1-kestose on the intestinal microbiota was investigated in cats. Six healthy cats were administered 1 g/day of 1-kestose for 8 weeks followed by a 2-week wash-out period. Fecal samples were collected from cats after 0, 4, 8, and 10 weeks. The intestinal microbiota was examined by a 16S rRNA gene metagenomic analysis and real-time PCR. Short-chain fatty acids were measured by GC/MS. The results suggested that the intestinal bacterial community structure in feline assigned to this study was divided into 2 types: one group mainly composed of the genus Lactobacillus (GA) and the other mainly composed of the genus Blautia with very few bacteria of Lactobacillus (GB). Furthermore, the number of Bifidobacterium slightly increased after the administration of 1-kestose (at 4 and 8 weeks) (P<0.1). The administration of 1-kestose also increased the abundance of Megasphaera, the butyric acid-producing bacteria, at 4 and 8 weeks (P<0.1). Furthermore, an increase in butyric acid levels was observed after the administration of 1-kestose for 4 weeks (P<0.1). These results suggest that 1-kestose activated butyrate-producing bacteria as well as bifidobacteria and propose its potential as a new generation prebiotic.

An Efficient New Process for the Selective Production of Odd-Chain Carboxylic Acids by Simple Carbon Elongation Using Megasphaera hexanoica.

The caproate-producing bacterium, Megasphaera hexanoica, metabolizes fructose to produce C2~C8 carbon-chain carboxylic acids using various electron acceptors. In particular, odd-chain carboxylic acids (OCCAs) such as valerate (C5) and heptanoate (C7), were produced at relatively high concentrations upon propionate supplementation. Using a statistical experimental design method, the optimal culture medium was established for the selective production of OCCAs among the total produced acids. In a medium containing 2.42 g L-1 sodium acetate and 18.91 g L-1 sodium propionate, M. hexanoica produced 9.48 g L-1 valerate, 2.48 g L-1 heptanoate, and 0.12 g L-1 caproate. To clarify the metabolism of the exogenous added propionate for OCCAs production, 13C tracer experiments were performed by supplementing the culture broth with [1,2,3-13C3] propionate. The metabolites analysis based on mass spectrometry showed that the propionate was only used to produce valerate and heptanoate without being participated in other metabolic pathways. Furthermore, the carbon elongation pathway in M. hexanoica was explained by the finding that the incorporation of propionate and acetate in the produced valerate occurred in only one orientation.

Alterations in gut bacterial and fungal microbiomes are associated with bacterial Keratitis, an inflammatory disease of the human eye.

Dysbiosis, or imbalance in the gut microbiome, has been implicated in auto-immune, inflammatory, neurological diseases as well as in cancers. More recently it has also been shown to be associated with ocular diseases. In the present study, the association of gut microbiome dysbiosis with bacterial Keratitis, an inflammatory eye disease which significantly contributes to corneal blindness, was investigated. Bacterial and fungal gut microbiomes were analysed using fecal samples of healthy controls (HC, n = 21) and bacterial Keratitis patients (BK, n = 19). An increase in abundance of several antiinflammatory organisms including Dialister, Megasphaera, Faecalibacterium, Lachnospira, Ruminococcus and Mitsuokella and members of Firmicutes, Veillonellaceae, Ruminococcaceae and Lachnospiraceae was observed in HC compared to BK patients in the bacterial microbiome. In the fungal microbiome, a decrease in the abundance of Mortierella, Rhizopus, Kluyveromyces, Embellisia and Haematonectria and an increase in the abundance of pathogenic fungi Aspergillus and Malassezia were observed in BK patients compared to HC. In addition, heatmaps, PCoA plots and inferred functional profiles also indicated significant variations between the HC and BK microbiomes, which strongly suggest dysbiosis in the gut microbiome of BK patients. This is the first study demonstrating the association of gut microbiome with the pathophysiology of BK and thus supports the gut-eye axis hypothesis. Considering that Keratitis affects about 1 million people annually across the globe, the data could be the basis for developing alternate strategies for treatment like use of probiotics or fecal transplantation to restore the healthy microbiome as a treatment protocol for Keratitis.

Megasphaera stantonii sp. nov., a butyrate-producing bacterium isolated from the cecum of a healthy chicken.

A novel mesophilic, anaerobic, Gram-stain-negative bacterium was isolated from the cecum of a healthy white leghorn chicken, and designated AJH120T. Cells were coccoid or diplococcoid with an average size of 0.8-1.8 µm and were non-motile with no evidence of spores. Phylogenetic analysis of 16S rRNA gene sequences revealed this organism to be a member of the genus Megasphaera, with the closest relatives being Megasphaera elsdenii (95 % sequence identity) and Megasphaera cerevisiae (95 % sequence identity). Growth was observed between 30 and 50 °C and between pH 5.0 and 9.0. AJH120T utilized a variety of carbon sources, including succinate, gluconate, fructose, ribose and pyruvate, as well as many individual amino acids. The DNA G+C content for the genome sequence of AJH120T was 52.1 mol%. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and average amino acid identity (AAI) between AJH120T and close taxonomic relatives, indicated divergence consistent with the strain representing a novel species. The major fatty acid methyl esters of the organism were C12 : 0, C14 : 0 3-OH, C18 : 1ω9c, C16 : 0 and C16 : 1ω9c. AJH120T was able to produce several short chain fatty acids, including butyrate, acetate, propionate and isovalerate. Together, these data indicate that AJH120T represents a novel species within the genus Megasphaera. We propose the name Megasphaerastantonii sp. nov. for the species. The type strain of this species is AJH120T (=DSM 106750T=CCUG 71842T).

Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients.

OBJECTIVES: The intestinal microbiota has been known to involve in obesity and host immune response. We aimed to investigate the intestinal microbiota and potential genetic function in relation to clinical presentation in psoriasis patients. METHODS: Faecal microbiota and predicted genetic function inferred from high-throughput 16S ribosomal RNA sequencing were analysed between psoriasis (n = 32) and age-, gender- and body mass index (BMI)-matched non-psoriasis subjects (n = 64), from a referral medical centre. The correlation between altered microbiota and disease activity, arthritis and systemic anti-psoriatic drugs was also investigated. RESULTS: We observed a distinct faecal microbial community structure in psoriasis patients, with an increased abundance of phylum Firmicutes and decreased abundance of phylum Bacteroidetes, across different subgroup of subjects. Ruminococcus and Megasphaera, of the phylum Firmicutes, were the top-two genera of discriminant abundance in psoriasis. A number of functional genes and metabolic pathways involving bacterial chemotaxis and carbohydrate transport were predicted over-represented, whereas genes related to cobalamin and iron transport were predicted under-represented in faecal microbiota of psoriasis patients. CONCLUSIONS: The distinct faecal microbial composition in psoriasis might be associated with altered transport of carbohydrate, cobalamin and iron, as well as chemotaxis.

New coculture system of Clostridium spp. and Megasphaera hexanoica using submerged hollow-fiber membrane bioreactors for caproic acid production.

In this study, a coculture bioprocess was developed with Clostridium strains producing butyric acid and Megasphaera hexanoica producing caproic acid from the butyric acid. The two bacterial strains were each cultivated in two submerged hollow-fiber membrane bioreactors (s-HF/MBRs), separately. Each fermentation broth was filtered through the membrane modules, and the filtered broth was either interchanged on another reactor or obtained sequentially through. Using s-HF/MBRs, the caproic acid concentration increased to 10.08 g L-1, with the fastest productivity of 0.69 g L-1 h-1, which higher than that previously reported.

Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid.

Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric acid was identified as a potential contributor to the HDAC inhibitory effects. This bacterial strain, Megasphaera massiliensis MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex community. M. massiliensis MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid. We here show that single bacterial strains from the human gut microbiota have potential as novel HDI therapeutics for disease areas involving host epigenetic aberrations.