Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal ...microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
Primary immunodeficiencies are heritable disorders of immune function. CD19 is a B cell co-receptor important for B cell development, and CD19 deficiency is a known genetic risk factor for a rare ...form of primary immunodeficiency known as "common variable immunodeficiency" (CVID); an antibody deficiency resulting in low levels of serum IgG and IgA. Enteropathies are commonly observed in CVID patients but the underlying reason for this is undefined. Here, we utilize CD19
mice as a model of CVID to test the hypothesis that antibody deficiency negatively impacts gut physiology under steady-state conditions. As anticipated, immune phenotyping experiments demonstrate that CD19
mice develop a severe B cell deficiency in gut-associated lymphoid tissues that result in significant reductions to antibody concentrations in the gut lumen. Antibody deficiency was associated with defective anti-commensal IgA responses and the outgrowth of anaerobic bacteria in the gut. Expansion of anaerobic bacteria coincides with the development of a chronic inflammatory condition in the gut of CD19
mice that results in an intestinal malabsorption characterized by defects in lipid metabolism and transport. Administration of the antibiotic metronidazole to target anaerobic members of the microbiota rescues mice from disease indicating that intestinal malabsorption is a microbiota-dependent phenomenon. Finally, intestinal malabsorption in CD19
mice is a gluten-sensitive enteropathy as exposure to a gluten-free diet also significantly reduces disease severity in CD19
mice. Collectively, these results support an effect of antibody deficiency on steady-state gut physiology that compliment emerging data from human studies linking IgA deficiency with non-infectious complications associated with CVID. They also demonstrate that CD19
mice are a useful model for studying the role of B cell deficiency and gut dysbiosis on gluten-sensitive enteropathies; a rapidly emerging group of diseases in humans with an unknown etiology.
Arsenicosis in a village in Bangladesh Ahmad, Sk. Akhtar; Sayed, M.H. Salim Ullah; Hadi, Sk. Abdul ...
International journal of environmental health research,
09/1999, Letnik:
9, Številka:
3
Journal Article
Recenzirano
The study was carried out in a village in Jessore district, Bangladesh, to identify the epidemiological characteristics of arsenicosis. Eighty-seven per cent of the tubewells had arsenic ...concentration more than the WHO maximum permissible limit of 0.05 mg l-1. The mean arsenic concentration was 0.240 mg l-1 and the maximum concentration was 1.371 mg l-1. Of the total 3606 villagers, 10% (363) were found to be suffering from arsenicosis. Most of the arsenicosis patients were between 10 to 39 years of age. There were more male patients (52.6%). There were no patients among villagers who consumed tubewell water having arsenic levels less than 0.082 mg l-1. The majority (93.4%) of the patients were in the first and second stage of arsenicosis. With increasing exposure to arsenic, a simultaneous increase in the severity of clinical manifestations of arsenicosis was observed (F = 43.699; p = 0.000). The time-weighted arsenic exposure varied from 0.248 to 5.482 mg day-1 and the mean was 1.918 mg day-1. Melanosis was present in almost all the patient (99.5%) and keratosis was present in 68.9%. Cancer (basal cell epithelioma) was present in three (0.8%) patients. The duration of clinical manifestations of arsenicosis varied from 1 to 12 years and the majority were suffering for 4-6 years.
Heavy metals contamination of fruits and vegetables is a growing concern to the public and policymakers in developing countries. This study investigated the extent of heavy metal contamination in ...widely consumed grape, apple, orange, banana, and pomegranate from supermarkets in Dhaka, Bangladesh, using atomic absorption spectroscopy (AAS) to assess the health risks to humans. Of the total 80% of banana and 60% of pomegranate samples, the mean lead (Pb) concentrations were 0.608 and 0.164, respectively, exceeding the maximum allowable concentration (MAC = 0.1) set by FAO/WHO and EU regulations, while the remaining fruit samples were below the limit. The Single-factor pollution index (PI) of Pb in bananas (6.08) and pomegranate (1.64) was higher than the reference value (PI>1), indicating the lower quality of fruits due to the higher amount of lead contents. The calculated incremental lifetime cancer risks (ILCRs) of cadmium (Cd) and Pb in banana, apple, grape, orange, and pomegranate for both children and i adults were exceeded the threshold limit (ILCR>10
−6
), which suggests that the consumption of heavy metal contaminated fruits poses potential cancer risks to the human health. In contrast, target hazard quotients (THQs) and chronic hazard index (HIs) values of all heavy metals were in the range of (THQ: 2.4 × 10
−6
-0.76; 6.5 × 10
−7
-0.20) and (HI:0.03-0.49; 0.01-0.13), respectively, for children and adults, which were below the acceptable limit (THQ<1), indicating no potential non-cancer risk for both consumer groups. These findings might help the policymakers and regulatory bodies concerned to apply control measures through monitoring the quality of locally grown or imported fruits available in supermarkets for human consumption.
With the advent of next-generation sequencing approaches, there has been a renaissance in the microbiome field. Microbial taxonomy and function can now be characterized relatively easily and ...rapidly—no longer mandating complex culturing approaches. With this renaissance, there is now a strong and growing appreciation for the role of the microbiome (referring to microbes and their genomes) in modulating many facets of physiology—including overall immunity. This is particularly true of the gut microbiome, and there is now an evolving body of the literature demonstrating a role for gut microbes in modulating responses to cancer treatment—particularly immunotherapy. Gut microbes can modulate immunity and anti-tumor responses via a number of different interactions, and these will be discussed herein. Additionally, data regarding the impact of gut microbes on cancer immunotherapy response will be discussed, as will strategies to manipulate the microbiome to enhance therapeutic responses. These efforts to date are not completely optimized; however, there is evidence of efficacy though much additional work is needed in this space. Nonetheless, it is clear that the microbiome plays a central role in health and disease, and strategies to manipulate it in cancer and overall precision health are being explored.
There is increasing appreciation of the microbial influence on cancer, with emerging evidence about the tumor microbiome and crosstalk with the gut microbiome. A great example of this is pancreatic ...cancer, in which intra-tumoral microbes such as bacteria and fungi have been shown to contribute to carcinogenesis and therapeutic responses, both positively and negatively.
There is increasing appreciation of the microbial influence on cancer, with emerging evidence about the tumor microbiome and crosstalk with the gut microbiome. A great example of this is pancreatic cancer, in which intra-tumoral microbes such as bacteria and fungi have been shown to contribute to carcinogenesis and therapeutic responses, both positively and negatively.
The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, ...modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.
Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a ...comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.
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