Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation

Cisplatin-induced nephrotoxicity is associated with gut microbiota disturbance. The present study aimed to investigate whether supplementation of Lactobacillus reuteri and Clostridium butyricum (LCs) had a protective effect on cisplatin-induced nephrotoxicity through reconstruction of gut microbiota. Wistar rats were given different treatments: control, cisplatin (Cis), cisplatin + C. butyricum and L. reuteri (Cis+LCs), and C. butyricum and L. reuteri (LCs). We observed that cisplatin-treated rats supplemented with LCs exhibited significantly decreased renal inflammation (KIM-1, F4/80, and MPO), oxidative stress, fibrosis (collagen IV, fibronectin, and a-SMA), apoptosis, concentration of blood endotoxin and indoxyl sulfate, and increased fecal butyric acid production compared with those without supplementation. In addition, LCs improved the cisplatin-induced microbiome dysbiosis by maintaining a healthy gut microbiota structure and diversity; depleting Escherichia-Shigella and the Enterobacteriaceae family; and enriching probiotic Bifidobacterium, Ruminococcaceae, Ruminiclostridium_9, and Oscillibacter. Moreover, the LCs intervention alleviated the cisplatin-induced intestinal epithelial barrier impairment. This study indicated LCs probiotic serves as a mediator of the gut–kidney axis in cisplatin-induced nephrotoxicity to restore the intestinal microbiota composition, thereby suppressing uremic toxin production and enhancing butyrate production. Furthermore, the renoprotective effect of LCs is partially mediated by increasing the anti-inflammatory effects and maintaining the integrity of the intestinal barrier.

A Series of Efficient Umbrella Modeling Strategies to Track Irradiation-Mutation Strains Improving Butyric Acid Production From the Pre-development Earlier Stage Point of View

Clostridium tyrobutyricum (C. tyrobutyricum) is a fermentation strain used to produce butyric acid. A promising new biofuel, n-butanol, can be produced by catalysis of butyrate, which can be obtained through microbial fermentation. Butyric acid has various uses in food additives and flavor agents, antiseptic substances, drug formulations, and fragrances. Its use as a food flavoring has been approved by the European Union, and it has therefore been listed on the EU Lists of Flavorings. As butyric acid fermentation is a cost-efficient process, butyric acid is an attractive feedstock for various biofuels and food commercialization products. 12C6+ irradiation has advantages over conventional mutation methods for fermentation production due to its dosage conformity and excellent biological availability. Nevertheless, the effects of these heavy-ion irradiations on the specific productiveness of C. tyrobutyricum are still uncertain. We developed non-structured mathematical models to represent the heavy-ion irradiation of C. tyrobutyricum in biofermentation reactors. The kinetic models reflect various fermentation features of the mutants, including the mutant strain growth model, butyric acid formation model, and medium consumption model. The models were constructed based on the Markov chain Monte Carlo model and logistic regression. Models were verified using experimental data in response to different initial glucose concentrations (0–180 g/L). The parameters of fixed proposals are applied in the various fermentation stages. Predictions of these models were in accordance well with the results of fermentation assays. The maximum butyric acid production was 56.3 g/L. Our study provides reliable information for increasing butyric acid production and for evaluating the feasibility of using mutant strains of C. tyrobutyricum at the pre-development phase.

Intestinal Anti-Inflammatory Improvement with Fenugreek Seeds as A prebiotic and Synbiotic with Lactobacillus acidophilus in Rats Experimentally Infected with Escherichia coli

Synergistic action of probiotics and prebiotics (synbiotic) has been suggested to be more effective than the two separate components in the prevention and treatment of many intestinal and immune diseases. The present study aimed to examine the anti-inflammatory role of Fenugreek as synbiotic with Lactobacillus acidophilus against Escherichia coli. Twenty four adult males of Wister rats aged 3-4 months and weighted 200-250 gm were used and divided into 4 groups: 1st and 2nd groups were negative and positive control (C and C++) fed with basal diet, the 3rd group (T1) fed diet with Fenugreek seeds (5%) and the 4th group (T2) fed with the synbiotic Fenugreek seeds (5%) and L. acidophilus (5 × 108 CFU/ml) for 45 days. After that, rats in the C++, T1, and T2 had induced enteritis by administrating 1 ml (2.5 × 106 cfu/ml) of enteropathogenic E. coli (EPEC O125:H6). The preventive role of prebiotic and synbiotic was evaluated depending on macro and microscopic duodenum pathological changes in correlation with butyric acid production for 7 days of infection. The results of the macro and microscopic scoring of enteritis revealed that the synergistic effects of the synbiotic in preventing E. coli enteritis was favored by an increase in goblet cells mucin secretion. This anti-inflammatory role was significantly increased by synbiotic and correlated with the production of butyric acid. The synbiotic improved the anti-inflammatory response of intestinal mucosa adaptive immunity via elevation of the immunoglobulin IgA from plasma cells. In conclusion, the inclusion of nutritional supplements containing fibers that constitute a source of butyric acid production, such as Fenugreek seeds, would improve intestinal resistance to inflammation by acting as anti-inflammatory through improving intestinal lymphoid tissues and increasing the production of IgA

Manipulation of saliva-derived microcosm biofilms to resemble dysbiotic subgingival microbiota

Periodontitis is a highly prevalent oral inflammatory disease triggered by dysbiotic subgingival microbiota. For the development of microbiome modulators that can reverse the dysbiotic state and re-establish a health-related microbiota, a high-throughput in vitro multi-species biofilm model is needed. Our aim is to establish a model that resembles a dysbiotic subgingival microbial biofilm by incorporating the major periodontal pathogen Porphyromonas gingivalis into microcosm biofilms cultured from pooled saliva of healthy volunteers. The biofilms were grown for 3, 7, and 10 days and analyzed for their microbial composition by 16S rDNA amplicon sequencing as well as dipeptidyl peptidase IV (DPP4) activity and butyric acid production. The addition of P. gingivalis increased its abundance in saliva-derived microcosm biofilms from 2.7% on day 3 to >50% on day 10, which significantly reduced the Shannon diversity, but did not affect the total number of operational taxonomic units (OTUs). The P. gingivalis-enriched biofilms displayed altered microbial composition as revealed by principle component analysis and reduced interactions among microbial species. Moreover, these biofilms exhibited enhanced DPP4 activity and butyric acid production. In conclusion, by adding P. gingivalis into saliva-derived microcosm biofilms, we established an in vitro pathogen-enriched dysbiotic microbiota, which resembles periodontitis-associated subgingival microbiota in terms of increased P. gingivalis abundance and higher DPP4 activity and butyric acid production. This model may allow for investigating factors that accelerate or hinder microbial shift from symbiosis to dysbiosis and for developing microbiome modulation strategies. IMPORTANCE In line with the new paradigm of the etiology of periodontitis, an inflammatory disorder initiated by dysbiotic subgingival microbiota, novel therapeutic strategies have been proposed, targeting reversing dysbiosis and restoring host-compatible microbiota, rather than eliminating the biofilms unselectively. Thus, appropriate laboratory models are required to evaluate the efficacy of potential microbiome modulators. In the present study, we used the easily obtainable saliva as an inoculum, spiked the microcosm biofilms with the periodontal pathogen Porphyromonas gingivalis, and obtained a P. gingivalis-enriched microbiota, which resembles the in vivo pathogen-enriched subgingival microbiota in severe periodontitis. This biofilm model circumvents the difficulties encountered when using subgingival plaque as the inoculum and achieves microbiota in dysbiotic state in a controlled and reproducible manner, which is required for high-throughput and large scale evaluation of strategies that can potentially modulate microbial ecology.