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It has now been established that a perturbation in gut microbiome composition exists in multiple sclerosis (MS) and its interplay with the immune system and brain could potentially contribute to the development of the disease and influence its course. The effects of the gut microbiota on the disease may be mediated by direct interactions between bacteria and immune cells or through interactions of products of bacterial metabolism with immune and CNS cells. In this review article we summarize the ways in which the gut microbiome of people with MS differs from controls and how bacterial metabolites can potentially play a role in MS pathogenesis, and examine approaches to alter the composition of the gut microbiota potentially alleviating gut dysbiosis and impacting the course of MS.

The utilization of fermentation media derived from waste and by-product streams from biodiesel and confectionery industries could lead to highly efficient production of bacterial cellulose. Batch fermentations with the bacterial strain Komagataeibacter sucrofermentans DSM (Deutsche Sammlung von Mikroorganismen) 15973 were initially carried out in synthetic media using commercial sugars and crude glycerol. The highest bacterial cellulose concentration was achieved when crude glycerol (3.2 g/L) and commercial sucrose (4.9 g/L) were used. The combination of crude glycerol and sunflower meal hydrolysates as the sole fermentation media resulted in bacterial cellulose production of 13.3 g/L. Similar results (13 g/L) were obtained when flour-rich hydrolysates produced from confectionery industry waste streams were used. The properties of bacterial celluloses developed when different fermentation media were used showed water holding capacities of 102–138 g·water/g·dry bacterial cellulose, viscosities of 4.7–9.3 dL/g, degree of polymerization of 1889.1–2672.8, stress at break of 72.3–139.5 MPa and Young’s modulus of 0.97–1.64 GPa. This study demonstrated that by-product streams from the biodiesel industry and waste streams from confectionery industries could be used as the sole sources of nutrients for the production of bacterial cellulose with similar properties as those produced with commercial sources of nutrients.

In this study, biochars (BC) from potato peel residuals were synthesized at 400, 600, and 800 °C, characterized, and evaluated for the persulfate-assisted oxidation of venlafaxine (VEN). BC pyrolyzed at 800 °C demonstrated the highest catalytic activity, resulting in the degradation of 750 μg/L of VEN in the presence of 500 mg/L persulfate in less than 90 min. Acidic conditions favored VEN destruction, while the apparent kinetic constant was reduced from 0.1136 at pH 3 to 0.0389 and 0.0352 min−1 for pH 7 and 9, respectively. Interestingly, the presence of inorganic ions such as bicarbonates and chlorides, as well as humic acid, only slightly reduced process efficiency. Scavenging tests and electron paramagnetic resonance spectroscopy indicate a mixed mechanism dominated by non-radical pathways, with minor radical contributions, mediated by oxygenated surface functionalities of the 800 °C biochar. Five transformation products were identified through LC-HRMS suspect and non-target approaches, and a potential degradation pathway was proposed. Most of the identified transformation products exhibited lower toxicity levels than the parent compound. Finally, life cycle analysis revealed that, despite its superior kinetics, the 800 °C biochar carries the largest environmental footprint, underscoring the need for integrated assessments that jointly optimize removal performance and environmental impacts.

Background Despite its high market potential, bio-based succinic acid production experienced recently a declining trend because the initial investments did not meet the expectations for rapid market growth. Thus, reducing the succinic acid production cost is imperative to ensure industrial implementation. Results Succinic acid production has been evaluated using hydrolysates from the organic fraction of municipal solid waste (OFMSW) collected from MSW treatment plants. A tailor-made enzymatic cocktail was used for OFMSW hydrolysate production containing up to 107.3 g/L carbon sources and up to 638.7 mg/L free amino nitrogen. The bacterial strains Actinobacillus succinogenes and Basfia succiniciproducens were evaluated for succinic acid production with the latter strain being less efficient due to high lactic acid production. Batch A. succinogenes cultures supplemented with 5 g/L yeast extract and 5 g/L MgCO3 reached 29.4 g/L succinic acid with productivity of 0.89 g/L/h and yield of 0.56 g/g. Continuous cultures at dilution rate of 0.06 h−1 reached 21.2 g/L succinic acid with yield of 0.47 g/g and productivity of 1.27 g/L/h. Downstream separation and purification of succinic acid was achieved by centrifugation, treatment with activated carbon, acidification with cation exchange resins, evaporation and drying, reaching more than 99% purity. Preliminary techno-economic evaluation has been employed to evaluate the profitability potential of bio-based succinic acid production. Conclusions The use of OFMSW hydrolysate in continuous cultures could lead to a minimum selling price of 2.5$/kg at annual production capacity of 40,000 t succinic acid and OFMSW hydrolysate production cost of 25 $ /t sugars.

Extracellular vesicles (EVs) are released by all cells, can cross the blood–brain barrier, and have been shown to play an important role in cellular communication, substance shuttling, and immune modulation. In recent years EVs have shifted into focus in multiple sclerosis (MS) research as potential plasma biomarkers and therapeutic vehicles. Yet little is known about the disease-associated changes in EVs in the central nervous system (CNS). To address this gap, we characterized the physical and proteomic changes of mouse spinal cord-derived EVs before and at 16 and 25 days after the induction of experimental autoimmune encephalomyelitis (EAE), a neuroinflammatory model of MS. Using various bioinformatic tools, we found changes in inflammatory, glial, and synaptic proteins and pathways, as well as a shift in the predicted contribution of immune and glial cell types over time. These results show that EVs provide snapshots of crucial disease processes such as CNS-compartmentalized inflammation, re/de-myelination, and synaptic pathology, and might also mediate these processes. Additionally, inflammatory plasma EV biomarkers previously identified in people with MS were also altered in EAE spinal cord EVs, suggesting commonalities of EV-related pathological processes during EAE and MS and overlap of EV proteomic changes between CNS and circulating EVs.

Deep eutectic solvents (DES) have been employed for the pretreatment of grape pomace and stalks within a biorefinery concept. Four DES, produced with choline chloride (ChCl) as hydrogen bond acceptor and four carboxylic acids as hydrogen bond donors, namely formic acid (FA), acetic acid (AA), lactic acid (LA) and oxalic acid (OA), were evaluated considering lignin removal efficiency, polysaccharide hydrolysis efficiency into C5 and C6 sugars, recyclability and reusability. The mixture of ChCl:LA at 1:10 molar ratio, 120°C and 1 h pretreatment, led to 40% lignin removal over four pretreatment cycles. Enzymatic hydrolysis of the remaining solids after the first pretreatment cycle resulted in 92.7% glucan and 36.6% hemicellulose hydrolysis yield. The hydrolysate was used as fermentation feedstock in batch Actinobacillus succinogenes bioreactor cultures leading to 36 g/L succinic acid with a yield of 0.62 g SA per g total sugars and 0.65 g/(L⋅h) productivity. Using 2 kg of grape pomace and stalks in each pretreatment cycle, the succinic acid that could be produced in five consecutive cycles is 200.8 g, 208 g, 204.9 g, 184.5 g and 94.3 g. Graphical Abstract

Background Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. Objective Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing–remitting MS (RRMS). Methods Thirty‐one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality‐of‐life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed‐effects models. Results Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p‐value <0.001, coefficient: −0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p‐value = 0.016, coefficient: −0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e‐01, 95% CI: 6.83e‐02, 9.09e‐01, p‐value = 3.15E‐02). Interpretation In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.

Background There is a paucity of studies examining quality of life (QoL) in people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods A cross-sectional, online, self-administered survey was distributed. Data elements included demographic and clinical characteristics, and QoL in Neurological Disorders (Neuro-QoL) short form questionnaires. Neuro-QoL domain scores were compared to reference populations, yielding standardized T-scores. Symptom severity was categorized as mild, moderate, or severe, using standard Neuro-QoL cut points. Results A total of 259 participants completed the survey. Neuro-QoL domain impairment was present in a significant proportion of respondents (anxiety: 58.1%, depression: 30.7%, stigma 29.8%, cognition: 58.5%, social function: 57.7%). T-scores were significantly worse than the reference population for anxiety (p<0.001), stigma (p=0.005), cognitive function (p<0.001) and social interactions (p<0.001). There was no clear association between QoL domains and demographics, disease-modifying therapy class, or type of clinical presentation. A relapsing vs monophasic disease course was associated with worse anxiety, stigma, cognition, and social interactions (p<0.05). Conclusion People with MOGAD may exhibit impairment in multiple domains of QoL. Practicing clinicians should be aware of this burden in MOGAD. Further research is needed to better understand factors associated with QoL impairment in MOGAD.

Background Unlike multiple sclerosis and neuromyelitis optica, the burden of fatigue in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unclear. Objective To compare fatigue levels between people with MOGAD and household controls (HC) and explore factors associated with fatigue severity. Methods In a cross-sectional survey, data were collected from people with MOGAD and HC by utilizing an online questionnaire. Data elements included demographics, sleep quality measures, comorbidities, MOGAD characteristics, and fatigue severity measured by the Modified Fatigue Impact Scale (MFIS). We compared fatigue severity between MOGAD participants and HC and assessed the associations between demographic and disease characteristics and fatigue severity. Results There were 180/283 MOGAD and 61/126 HC respondents. Compared to HC, people with MOGAD reported more severe fatigue, as measured by the MFIS total score (49.3 vs. 36.5; p < 0.001), and a larger proportion of MOGAD participants (75.6% vs. 44.3%; p < 0.001) were classified as fatigued. Among MOGAD participants, higher age (p = 0.04), history of bilateral optic neuritis (p = 0.02), and current use of acute treatment (p = 0.04) were independently associated with higher fatigue. Conclusions Fatigue is common in people with MOGAD, and a history of bilateral optic neuritis, comorbid conditions, and ongoing disease activity appear to contribute to fatigue severity.

Cheese whey (CW) constitutes a dairy industry by-product, with considerable polluting impact, related mostly with lactose. Numerous bioprocessing approaches have been suggested for lactose utilization, however, full exploitation is hindered by strain specificity for lactose consumption, entailing a confined range of end-products. Thus, we developed a CW valorization process generating high added-value products (crude enzymes, nutrient supplements, biopolymers). First, the ability of Aspergillus awamori to secrete β-galactosidase was studied under several conditions during solid-state fermentation (SSF). Maximum enzyme activity (148 U/g) was obtained at 70% initial moisture content after three days. Crude enzymatic extracts were further implemented to hydrolyze CW lactose, assessing the effect of hydrolysis time, temperature and initial enzymatic activity. Complete lactose hydrolysis was obtained after 36 h, using 15 U/mL initial enzymatic activity. Subsequently, submerged fermentations were performed with the produced hydrolysates as onset feedstocks to produce bacterial cellulose (5.6–7 g/L). Our findings indicate a novel approach to valorize CW via the production of crude enzymes and lactose hydrolysis, aiming to unfold the output potential of intermediate product formation and end-product applications. Likewise, this study generated a bio-based material to be further introduced in novel food formulations, elaborating and conforming with the basic pillars of circular economy.