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Lower bone mineral density (BMD) constitutes a common issue in inflammatory bowel disease (IBD). Studies often explore the association between BMD and folic acid level. The presented study aimed to evaluate the impact of MTHFRgene polymorphism and folic acid levels on BMD in patients with IBDs: Crohn’s disease (CD) and ulcerative colitis (UC). The study group comprised IBD patients and a healthy control group. BMD, T-score, and Z-score of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry. Folic acid level was determined using direct chemiluminescence, and the MTHFR677C > T (rs1801133) and 1298A > C (rs1801131) genotyping were performed by HRMA. Our study found no significant differences in the folic acid levels between the groups. Patients with CD and UC presented a lower BMD, T-score, and Z-score of the FN and L1-L4 than the CG. UC patients who were homozygotes AA in loci c.1298A>C presented lower than controls lumbar spine L1-L4 BMD and T-score values. Regarding MTHFR677 polymorphism, we found that IBD patients carrying CC genotype demonstrated lower than controls femoral neck Z-score, lumbar spine L1-L4 BMD, T-score and Z-score. MTHFRpolymorphisms were found to have no impact on folic acid concentrations. IBD patients presented a higher risk of low BMD than the healthy controls, regardless of MTHFR677 and 1298 genotypes. However, MTHFRpolymorphism may influence on bone in IBD patients. Nevertheless, it appears essential to conduct further studies.

Anti-tumor necrosis factor (TNF) therapy is used to induce and maintain remission in Crohn’s disease (CD) patients. However, primary non-responders to initial treatment constitute 20–40% of cases. The causes of this phenomenon are still unknown. We aim to investigate the impact of the caspase 9 (CASP9) gene variants on the variable reactions of CD patients to anti-TNF therapy. The study group included 196 diagnosed and clinically characterized CD Polish patients following anti-TNF therapy. The sequence of the CASP9gene was analyzed using next-generation and Sanger sequencing and was analyzed with the response to biological treatment. Using the RT-qPCR analysis, we estimated the CASP9gene mRNA level in colon biopsies material from inflamed and non-inflamed tissue (21 CD patients: 14 responders and seven non-responders to anti-TNF therapy and six controls), as well as in vitro in a peripheral blood mononuclear cells (PBMCs) from CD patients (seven responders and seven non-responders to anti-TNF therapy) and eight controls. Our findings indicated association of variants rs1052571 and rs4645978 with response to anti-TNF monoclonal antibodies (mAbs). Moreover, we observed tendency for reduced expression after incubation with anti-TNF in the group of CD patients, in contrast to the control group. Our results suggest that response to anti-TNF therapy in CD patients may be an effect of variants of the CASP9gene as a key effector of the internal pathway of apoptosis; however, further population and functional research are necessary.

The abnormal accumulation of visceral adipose tissue in obesity is associated with metabolic changes that include altered glucose tolerance, insulin resistance, hyperlipidemia, and metabolic syndrome. Obesity also coincides with increased incidence of autoimmune diseases. Accumulating evidence suggest that prolonged metabolic overload related to overnutrition, influenced by genetic and epigenetic factors, might affect immunologic self-tolerance through changes in the energy metabolism of immune cells, particularly regulatory T (Treg) cells. A strong activation of nutrient-energy signaling pathways blocks the induction of the transcription factor forkhead P3 (FOXP3), a master regulator of Treg cells, consequently inhibiting their generation and proliferation, thereby promoting proinflammatory response. Expanding our knowledge on the topic, particularly on metabolic T cell flexibility in vivowill provide new insights that can be used to develop therapeutic strategies for various inflammatory diseases, including obesity and autoimmune diseases. Targeting specific metabolic pathways is emerging as an important approach to control immune response and maintain immunological homeostasis.

Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in transfats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (ɷ-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.Statement of Significance: This manuscript provides the current knowledge and a holistic view of diet and supplementation with regard to female fertility.

Infertility is an increasing problem that affects couples attempting pregnancy. A growing body of evidence points to a link between diet and female fertility. In fact, data show that a diet high in transfats, refined carbohydrates, and added sugars can negatively affect fertility. Conversely, a diet based on the Mediterranean dietary patterns, i.e., rich in dietary fiber, omega-3 (ɷ-3) fatty acids, plant-based protein, and vitamins and minerals, has a positive impact on female fertility. An unhealthy diet can disrupt microbiota composition, and it is worth investigating whether the composition of the gut microbiota correlates with the frequency of infertility. There is a lack of evidence to exclude gluten from the diet of every woman trying to become pregnant in the absence of celiac disease. Furthermore, there are no data concerning adverse effects of alcohol on female fertility, and caffeine consumption in the recommended amounts also does not seem to affect fertility. On the other hand, phytoestrogens presumably have a positive influence on female fertility. Nevertheless, there are many unanswered questions with regard to supplementation in order to enhance fertility. It has been established that women of childbearing age should supplement folic acid. Moreover, most people experience vitamin D and iodine deficiency; thus, it is vital to control their blood concentrations and consider supplementation if necessary. Therefore, since diet and lifestyle seem to be significant factors influencing fertility, it is valid to expand knowledge in this area.

Biological therapy with anti-tumor necrosis factor-α (anti-TNF-α) monoclonal antibodies significantly increased the effectiveness of autoimmune disease treatment compared with conventional medicines. However, anti-TNF-α drugs are relatively expensive and a response to the therapy is reported in only 60–70% of patients. Moreover, in up to 5% of patients adverse drug reactions occur. The various effects of biological treatment may be a potential consequence of interindividual genetic variability. Only a few studies have been conducted in this field and which refer to single gene loci. Our aim was to design and optimize a methodology for a broader application of pharmacogenetic studies in patients undergoing anti-TNF-α treatment. Based on the current knowledge, we selected 16 candidate genes: TNFRSF1A, TNFRSF1B, ADAM17, CASP9, FCGR3A, LTA, TNF, FAS, IL1B, IL17A, IL6, MMP1, MMP3, S100A8, S100A9, and S100A12, which are potentially involved in the response to anti-TNF-α therapy. As a research model, three DNA samples from Crohn’s disease (CD) patients were used. Targeted genomic regions were amplified in 23 long-range (LR) PCR reactions and after enzymatic fragmentation amplicon libraries were prepared and analyzed by next-generation sequencing (NGS). Our results indicated 592 sequence variations located in all fragments with coverage range of 5–1089. We demonstrate a highly sensitive, flexible, rapid, and economical approach to the pharmacogenetic investigation of anti-TNF-α therapy using amplicon libraries and NGS technology.

The prevalence of obesity has recently increased dramatically and has contributed to the increasing prevalence of various pathological conditions, including type 2 diabetes mellitus, nonalcoholic fatty liver disease, asthma, various types of cancer, cardiovascular and neurodegenerative diseases, and others. Accumulating evidence points to localized inflammation in adipose tissue, which, in turn, promotes systemic low-grade inflammation as a primary force contributing to the development of these pathologies. A better understanding of the underlying mechanisms behind obesity-induced adipose tissue inflammation is required to develop effective therapeutic or prophylactic strategies. This review is aimed to present the current knowledge of adipose tissue inflammation associated with obesity.

This study aimed to compare the accuracy of selected laboratory markers in assessing disease activity in patients with ulcerative colitis (UC). The analysis included serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ, hsCRP, peripheral regulatory T cells, as well as fecal calprotectin and lactoferrin. A group of 45 adults with UC was enrolled in the study. Disease activity was assessed using the Mayo endoscopic index, while for clinical activity scoring, the Clinical Activity Index (CAI) was used. Concentrations of markers investigated were estimated by means of flow cytometry and enzyme-linked immunosorbent assays: the results were correlated with both indices. The study demonstrated that both fecal markers, i.e. calprotectin (r = 0.880, P<0.001) and lactoferrin (r = 0.799, P<0.001) correlated closely with the Mayo endoscopic score, and might be used to evaluate the severity of UC in the clinical setting. The correlation of these markers with CAI was also significant, with r = 0.831 for calprotectin (P<0.001) and r = 0.672 for lactoferrin (P<0.05). As for the other markers investigated, only IL-6 (r = 0.598, P<0.001), IL-17A (r = 0.587, P<0.005), and TNF-α (r = 0.701, P<0.001) correlated closely with the Mayo endoscopic index. The correlation of the markers with CAI was also significant, though weaker, with r = 0.525 for IL-6 (P<0.001), r = 0.587 for IL-17A (P<0.05), and r = 0.624 for TNF-α (P<0.001). Despite the fact, that UC is generally considered to be an IL-13-driven, Th2-like type of disease, markers of inflammation such as serum interleukin (IL)-6, IL-17, TNF-α, fecal calprotectin and lactoferrin might be useful in assessing disease activity.

Primary intestinal lymphangiectasia (PIL) is a rare protein-losing gastroenteropathy of unknown etiology, characterized by impaired lymphatic vessels drainage. The pathological changes in PIL result in usually localized or diffuse dilatation of intestinal lacteals, leading to leakage of lymphatic fluid rich of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. PIL may be asymptomatic or mildly symptomatic in moderate forms of the disease. In some patients, though, the outcome may be poor or even life-threatening. This case report demonstrates the severity of protein malnutrition, in some cases, and the extent of GI tract affected, requiring to start PN early and the need for its continuation as home parenteral nutrition (HPN).