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Recent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes. In this review, we first discuss how dysbiosis of the intestinal microbiota is linked to human disease development and how potential modulation strategies of the gut microbial ecosystem can be used for disease treatment. In addition, we introduce categories and workflows of different machine learning approaches, and how they can be used to perform integrative analysis of multi-omics data. Finally, we review advances of machine learning in gut microbiome applications and discuss related challenges. Based on this we conclude that machine learning is very well suited for analysis of gut microbiome and that these approaches can be useful for development of gut microbe-targeted therapies, which ultimately can help in achieving personalized and precision medicine.

Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.

Background Limosilactobacillus reuteri (earlier known as Lactobacillus reuteri ) is a well-studied lactic acid bacterium, with some specific strains used as probiotics, that exists in different hosts such as human, pig, goat, mouse and rat, with multiple body sites such as the gastrointestinal tract, breast milk and mouth. Numerous studies have confirmed the beneficial effects of orally administered specific L. reuteri strains, such as preventing bone loss and promoting regulatory immune system development. L. reuteri ATCC PTA 6475 is a widely used strain that has been applied in the market as a probiotic due to its positive effects on the human host. Its health benefits may be due, in part, to the production of beneficial metabolites. Considering the strain-specific effects and genetic diversity of L. reuteri strains, we were interested to study the metabolic versatility of these strains. Results In this study, we aimed to systematically investigate the metabolic features and diversities of L. reuteri strains by using genome-scale metabolic models (GEMs). The GEM of L. reuteri ATCC PTA 6475 was reconstructed with a template-based method and curated manually. The final GEM i HL622 of L. reuteri ATCC PTA 6475 contains 894 reactions and 726 metabolites linked to 622 metabolic genes, which can be used to simulate growth and amino acids utilization. Furthermore, we built GEMs for the other 35  L. reuteri strains from three types of hosts. The comparison of the L. reuteri GEMs identified potential metabolic products linked to the adaptation to the host. Conclusions The GEM of L. reuteri ATCC PTA 6475 can be used to simulate metabolic capabilities and growth. The core and pan model of 35  L. reuteri strains shows metabolic capacity differences both between and within the host groups. The GEMs provide a reliable basis to investigate the metabolism of L. reuteri in detail and their potential benefits on the host.

Background The prognosis of patients with progressive or recurrent high-grade gliomas (HGGs) after surgery remains poor. Iodine-125 brachytherapy is emerging as a salvage method for the treatment of gliomas. This study aimed to investigate whether permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection. Methods Between March 2004 and August 2016, 58 patients with progressive or recurrent HGG after gross total resection were included in this study. Twenty-nine patients underwent radiotherapy and/or chemotherapy and then permanent iodine-125 brachytherapy (SRCI group). Twenty-nine patients underwent permanent iodine-125 brachytherapy alone (SI group). Follow-up was carried out at 1, 3, and 6 months and then at 1, 2, 3, and 5 years after iodine-125 implantation. The median overall survival (OS) and progression-free survival (PFS), procedure-related complications and clinical outcomes were evaluated. Results No procedure-related fatal events happened. The temporary morbidity rate was 11.9%. The median OS and PFS for patients in the SI group were 22 and 8 months compared with 21 and 7 months in the SRCI group. No significant differences were found. Age and Karnofsky Performance Status (KPS) were independent prognostic factors for OS. Age, KPS and histology were independent prognostic factors for PFS. Conclusions Permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection.

Purpose In this study, we retrospectively investigated the prognostic role of pre-treatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in esophageal squamous cell carcinoma patients (ESCC) treated with concurrent chemo-radiotherapy (CCRT). Methods We retrospectively analyzed the records of 338 patients with pathologically diagnosed esophageal squamous cell carcinoma that underwent concurrent chemo-radiotherapy from January 2013 to December 2017. Univariate and multivariate analyses were used to identify prognostic factors for progression free survival (PFS) and overall survival (OS). Results The result showed that the thresholds for NLR and PLR were 2.47 and 136.0 by receiver operating characteristic curve. High NLR and PLR were both associated with tumor length ( P  < 0.05). High NLR and PLR were significantly associated with poor PFS and OS. Multivariate analyses identified NLR, PLR and TNM stage were independent risk factors for PFS and OS. Conclusions We show that the pre-treatment NLR and PLR may serve as prognostic indicators for esophageal squamous cell carcinoma treated with concurrent chemo-radiotherapy.

Objective To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. Methods This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. Results Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p < 0.001). The mean preoperative daily morphine consumption was 108.95 ± 56.41 mg, which decreased to 50.13 ± 25.46 mg at 24 h, 31.18 ± 18.58 mg at 1 week, 22.50 ± 16.63 mg at 4 weeks, 21.71 ± 17.68 mg at 12 weeks, and 17.27 ± 16.82 mg at 24 weeks postoperatively (all p < 0.001). During the follow-up period, the Oswestry Disability Index scores significantly reduced (p < 0.001). Bone cement leakage occurred in 25 vertebral bodies, with an incidence of 39.7% (25/63). Conclusions The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases.

Over 100 genome-scale metabolic networks (GSMNs) have been published in recent years and widely used for phenotype prediction and pathway design. However, GSMNs for a specific organism reconstructed by different research groups usually produce inconsistent simulation results, which makes it difficult to use the GSMNs for precise optimal pathway design. Therefore, it is necessary to compare and identify the discrepancies among networks and build a consensus metabolic network for an organism. Here we proposed a process for systematic comparison of metabolic networks at pathway level. We compared four published GSMNs of Pseudomonas putida KT2440 and identified the discrepancies leading to inconsistent pathway calculation results. The mistakes in the models were corrected based on information from literature so that all the calculated synthesis and uptake pathways were the same. Subsequently we built a pathway-consensus model and then further updated it with the latest genome annotation information to obtain modelPpuQY1140 for P. putida KT2440, which includes 1140 genes, 1171 reactions and 1104 metabolites. We found that even small errors in a GSMN could have great impacts on the calculated optimal pathways and thus may lead to incorrect pathway design strategies. Careful investigation of the calculated pathways during the metabolic network reconstruction process is essential for building proper GSMNs for pathway design.

Background The spine is the most frequently affected part of the skeletal system to metastatic tumors. External radiotherapy is considered the first-line standard of care for these patients with spine metastases. Recurrent spinal metastases after radiotherapy cannot be treated with further radiotherapy within a short period of time, making treatment difficult. We aimed to evaluate the effectiveness and safety of MWA combined with cementoplasty in the treatment of spinal metastases after radiotherapy under real-time temperature monitoring. Methods In this retrospective study, 82 patients with 115 spinal metastatic lesions were treated with MWA and cementoplasty under real-time temperature monitoring. Changes in visual analog scale (VAS) scores, daily morphine consumption, and Oswestry Disability Index (ODI) scores were noted. A paired Student’s t-test was used to assess these parameters. Complications during the procedure were graded using the CTCAE version 5.0. Results Technical success was attained in all patients. The mean VAS score was 6.3 ± 2.0 (range, 4–10) before operation, and remarkable decline was noted in one month (1.7 ± 1.0 [ P  < .001]), three months (1.4 ± 0.8 [ P  < .001]), and six months (1.3 ± 0.8 [ P  < .001]) after the operation. Significant reductions in daily morphine consumption and ODI scores were also observed ( P  < .05). Cement leakage was found in 27.8% (32/115) of lesions, with no obvious associated symptoms. Conclusion MWA combined with cementoplasty under real-time temperature monitoring is an effective and safe method for recurrent spinal metastases after radiotherapy.

Background: To compare the safety and efficacy of 2 different computed tomography-guided puncture techniques for simultaneous needle biopsy and microwave ablation of suspected malignant pulmonary nodules. Methods: This retrospective comparative before-and-after study analyzed the data of 81 patients (each with a suspected malignant pulmonary nodule) who underwent computed tomography-guided needle biopsy with simultaneous microwave ablation between September 2016 and September 2021. In group A, 41 patients (41 pulmonary nodules) underwent microwave ablation immediately through the biopsy channel, whereas in group B, 40 patients (40 pulmonary nodules) underwent computed tomography-guided percutaneous needle biopsy and microwave ablation through separate needle channels. Clinical data, technical success rates, complications, and short-term efficacy were compared between the groups to evaluate the advantages and disadvantages of both techniques. Results: Of the 81 patients, 78 successfully underwent needle biopsy and microwave ablation, with a technical success rate of 96.3%. The incidence of pneumothorax was 56.1% (23 out of 41) and 30% (12 out of 40) in groups A and B, respectively, while that of chest pain was 34.1% (14 out of 41) and 40% (16 out of 40) in groups A and B, respectively. The differences were statistically insignificant (p = .127 and p = .759). However, the incidence of hemoptysis was 39.0% (16 out of 41) and 17.5% (7 out of 40), respectively, which was statistically significant (P = .015). Air embolism, bronchopleural fistula, and needle implantation metastasis were not observed in both groups. At a 6-month follow-up, there were no other complications in both groups, and complete ablation was observed in all cases. Conclusion: Computed tomography-guided biopsy combined with microwave ablation is safe and effective for the treatment of suspected malignant pulmonary nodules, and clinicians can use both techniques.

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