Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.

Gut Microbiota Mediates Lactobacillus rhamnosus GG Alleviation of Deoxynivalenol-Induced Anorexia.

Deoxynivalenol (DON) is a widespread mycotoxin and causes anorexia and emesis in humans and animals; Lactobacillus rhamnosus GG (LGG), a well-characterized probiotic, can improve intestinal barrier function and modulate immune response. Currently, it is unclear whether LGG has a beneficial effect on DON-induced anorexia. In the present study, mice were treated with DON, LGG, or both by gavage for 28 days to evaluate the effects of LGG on DON-induced anorexia. Antibiotic treatment and fecal microbiota transplant (FMT) experiment were also conducted to investigate the link between DON, LGG, and gut microbiota. LGG significantly increased the villus height and reduced the crypt depth in jejunum and ileum, enhanced the tight junction proteins expression in the intestine, and regulated the TLR4/NF-κB signaling pathway, consequently attenuating the intestinal inflammation caused by DON. In addition, LGG increased the relative abundance of Lactobacillus and butyric acid production of cecal contents; remodeled phenylalanine metabolism and tryptophan metabolism; reduced plasma peptide tyrosine tyrosine (PYY), 5-hydroxytryptamine (5-HT), and glucagon-like peptide-1 (GLP-1) concentrations; and promoted hypothalamic NPY and AgPR gene expression, which will further promote food intake and reduce weight loss, ultimately alleviating DON-induced anorexia in mice. Interestingly, antibiotic treatment diminished the intestinal toxicity of DON. The FMT experiment showed that DON-originated microbiota promotes intestinal inflammation and anorexia, while LGG + DON-originated microbiota has no adverse effects on mice. Both antibiotic treatment and FMT experiment have proved that gut microbiota was the primary vector for DON to exert its toxic effects and an essential mediator of LGG protection. In summary, our findings demonstrate that gut microbiota plays essential roles in DON-induced anorexia, and LGG can reduce the adverse effects caused by DON through its structure and regulate the gut microbiota, which may lay the important scientific foundation for future applications of LGG in food and feed products.

Gut microbial short-chain fatty acids-mediated olfactory receptor 78 stimulation promotes anorexigenic gut hormone peptide YY secretion in mice.

Olfactory receptor 78 (Olfr78), which is also known as a receptor for short-chain fatty acids (SCFAs) produced via gut microbial fermentation from indigestible polysaccharides such as dietary fibers, is expressed in the enteroendocrine cells of the colon. However, the role of Olfr78 in gut hormone secretion remains unknown. Here, we aimed to investigate the function and mechanism of action of Olfr78 in vivo and in vitro. Toward this, we assessed the expression of Olfr78 in several tissues, affinity of Olfr78 to various monocarboxylates, and the secretion of anorexigenic gut hormone peptide YY (PYY) via Olfr78 using various molecular and biochemical techniques. Olfr78 was abundantly expressed in the colon and mouse enteroendocrine cell line STC-1 and showed specific affinity to SCFAs such as acetate and propionate, but not butyrate, in a monocarboxylate ligand screening assay using a heterologous expression system. Acetate promoted PYY secretion in STC-1 cells via Olfr78-protein kinase A signaling, whereas the effects were abolished by Olfr78 RNA interference. Colonic SCFAs production via oral administration of fructo-oligosaccharide significantly increased plasma PYY levels, whereas this effect was abolished in Olfr78-deficient and germ-free mice. These results suggested that the SCFA receptor Olfr78 is important for anti-obesity and anorexigenic effects of the gut microbiota and dietary fibers.

CD8 T cells drive anorexia, dysbiosis, and blooms of a commensal with immunosuppressive potential after viral infection.

Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.

Proteome modifications of gut microbiota in mice with activity-based anorexia and starvation: Role in ATP production.

OBJECTIVE: Activity-based anorexia (ABA) in rodents is a behavioral model of anorexia nervosa, characterized by negative energy balance, hyperactivity, and dysbiosis of gut microbiota. Gut bacteria are known to produce energy substrates including adenosine triphosphate (ATP) and acetate. The aim of this study was to determine whether ABA alters the proteome of gut microbiota relevant to ATP and acetate production. METHODS: The ABA was developed in male mice and compared with food-restricted and ad libitum-fed conditions. Proteomic analysis of feces was performed using the two-dimentional gel electrophoresis and mass spectrometry. The in vitro ATP-producing capacity of proteins extracted from feces was assayed. RESULTS: Increased levels of the phosphoglycerate kinase, an ATP-producing glycolytic enzyme, was detected in feces of food-restricted mice and this enzyme was further increased in the ABA group. Starvation also upregulated several other proteins synthetized by order Clostridiales including Clostridiaceae and Lachnospiraceae families. No significant differences in the in vitro ATP-producing capacity by bacterial proteins from ABA, food-restricted, and ad libitum-fed control mice were found. However, plasma levels of acetate strongly tended to be increased in the activity groups including ABA mice. CONCLUSION: The data revealed that starvation in food-restricted and ABA mice induced proteome modification in gut bacteria favoring ATP production mainly by the order Clostridiales. However, this did not result in increased total ATP-production capacity by gut microbiota. These changes can be interpreted as an adaptation of specific gut bacteria to the host malnutrition beneficial for host survival.

Clinical profile of tuberculosis in patients with chronic kidney disease: A report from an endemic Country.

The objective is to study the clinical profile of tuberculosis (TB) in chronic kidney disease (CKD). This is retrospective study of CKD patients who were diagnosed to have TB over a period of seven years at a tertiary care hospital. TB was diagnosed in 115 patients with an incidence of 4200/100,000. Mean age of the patients was 46.9 ± 16 years. Sixty-two patients (53.9%) were male. Causes of CKD were diabetic nephropathy and hypertension in 11.3% each, chronic glomerulonephritis in 31.3%, chronic tubulointerstitial nephritis in 39.1%, autosomal dominant polycystic kidney disease, and post-renal transplant CKD in 3.5% each. About 68.7% of patients with TB had advanced CKD stage of 4-5D, whereas 31.3% of patients had early CKD stage 1-3. Twenty percent of patients were on dialysis. Three-fourths of the patients had extrapulmonary TB. Pleuropulmonary (41.8%), kidney and urinary tract (20%), and abdomen and lymph node (13% each) were the most common sites for TB. The main clinical presentation of TB was: fever/pyrexia of unknown origin in 24.3%, constitutional symptoms of anorexia, fever, night sweats, and weight loss in 27.8%, abnormal chest radiograph in 31.2%, ascites/peritonitis in 13.9%, pleural effusion in 25.2%, lymphadenopathy in 20%, and sterile pyuria/hematuria/chronic pyelonephritis in 13%. Microbiological and/or histopathological diagnoses were made in 45.2% and in the other 54.8%, diagnosis of TB was made on clinical grounds. Adverse effects of anti-TB drugs were seen in 9.6% of patients. Ninety-three percent completed the treatment and survived. Eight patients (7%), all in CKD stage 5D, died. The incidence of TB was high among CKD stages 4 and 5 and in those receiving dialysis. Extrapulmonary disease such as pleuropulmonary, renal, peritoneal, and lymph node were the common forms of TB.

Diagnosis of clinically suspected and unsuspected tubercular lymphadenopathy by cytology, culture, and smear microscopy.

BACKGROUND: Tubercular lymphadenopathy (TBLN) accounts for 20-40% cases of extrapulmonary tuberculosis. But the common presenting symptoms of tuberculosis like fever, cough, weight loss, fatigue, and night sweats are not always associated with tuberculosis lymphadenopathy, thereby, making its diagnosis difficult. Our aim was to study if Fine Needle Aspiration Cytology (FNAC) combined with Zeihl Neelsen stain and culture for Mycobacterium tuberculosis bacilli could improve the diagnostic accuracy in patients clinically suspected and unsuspected for tubercular lymphadenitis. METHODS: The study was conducted at Department of Pathology, Acharya Vinoba Bhave Rural Hospital, Jawaharlal Nehru medical College, Wardha, India. One hundred and twenty-nine patients with enlarged lymph node for more than two weeks duration were evaluated. All the patients were subjected to cytology, smear, and culture examination of their lymph node aspirate. RESULTS: Age range for the patients was from 1 to 74 years (mean 30.49±16.69) and F:M ratio was 1:1.18. Most common site of involvement was cervical lymph node. 48 patients were diagnosed as TBLN, out of which 19 patients had no associated symptoms and 28 patients had one or more presenting symptoms of tuberculosis. Fever was the most common presenting symptoms. Pediatric age group patients were more commonly associated with symptoms than adults (p value=0.000). Culture and ZN stain were positive in 32 and 10 cases respectively among TBLN. Additionally, culture was positive in 20 patients diagnosed as reactive lymphoid hyperplasia. CONCLUSION: Cytology combined with culture improves the diagnostic accuracy in cases with enlarged lymph nodes, suspected or unsuspected for tuberculosis.

Review of mechanisms of deoxynivalenol-induced anorexia: The role of gut microbiota.

Deoxynivalenol (DON) is one of the most important mycotoxins in cereal-based foods or other food productions, produced by Fusarium species. Because of the high occurrence of DON in food combined with vast consumption of cereals and grain worldwide, the DON-contaminated food is a very harmful factor for human and animal health. DON has been reported to induce anorexia at lower or chronic doses in animal models. However, further researches for DON-induced anorexia are limited. Previous publications demonstrated a close link between Bacteroidetes and Firmicutes, two kinds of gut microbiota, with weight loss and the effect of low administration of DON on neurotransmitters in the frontal cortex, cerebellum, hypothalamus, hippocampus and pons/medulla. These data are similar to other studies, which show selective 5HTα receptor agonists apparently causing hyperphagia whereas 5HT1ß agonists appear to induce anorexia. Thus, the neurochemical effects of lower DON exposure can be as a result of peripheral toxicological events such as emesis, which overwhelmed its more subtle feed refusal activity. Besides, changes in the microbiota have an impact on stress-related behaviors like anxiety and depression, which can lead to weight loss through decreased feed intake. Gut dysbiosis is also associated with brain dysfunction and with behavioral changes. These conclusions illustrate as well a potential explanation for DON-induced anorexia.In this review, we summarize information about DON-induced anorexia from previous studies and provide our opinion for future investigations that could establish a link between gut microbiota, neurotransmitters, anorexia and weight loss under the DON exposure. Copyright © 2017 John Wiley & Sons, Ltd.

Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1ß-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence.

Disease Tolerance Trick or Treat: Give Your Brain Something Good to Eat.

The reprioritization of feeding motivations during disease is proposed to optimize host defense strategies against infection. Now, Wang et al. identify that sickness-induced anorexia differentially shapes the metabolic requirements of cellular stress adaptations, leading to opposite impact on disease tolerance upon bacterial versus viral infections.

Synchronous presentation of two rare forms of extrapulmonary tuberculosis.

Tuberculosis (TB) remains one of the leading infectious causes of death throughout the world. Extrapulmonary forms, namely adrenalitis and prostatitis, are rare presentations of TB and pose a difficult diagnostic challenge, given their non-specific manifestations. The authors present a case of a 42-year-old man with long-standing symptoms of fatigue, anorexia, weight loss, nightly fever and sudoresis. He also suffered from sporadic vomiting and episodic hypotension, and had skin hyperpigmentation, as well as frequent urination, perineal discomfort and pain at ejaculation. Laboratory investigation confirmed primary adrenal failure. On CT scan there were two hypodense right adrenal nodules and bilateral lung condensations with a tree-in-bud pattern. Another hypodense nodule was seen in the prostate. TB was diagnosed by isolatingMycobacterium tuberculosisfollowing cultures of bronchoalveolar lavage, bronchial secretions, urine and ejaculate. Antibacillary treatment resolved the infectious lesions but the patient remained on corticosteroid replacement therapy for ongoing adrenal failure.

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice.

Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR(Ser2448) and p70S6K(Thr389). We also showed that LPS administration increased the phosphorylation of FOXO1(Ser256), the p65 subunit of nuclear factor kappa B (P<0.05), and FOXO1/3a(Thr) (24) (/) (32) (P<0.01). Blocking the mTOR pathway significantly attenuated the LPS-induced anorexia by decreasing the phosphorylation of p70S6K(Thr389), FOXO1(Ser256), and FOXO1/3a(Thr) (24) (/) (32). These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia.

Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness.

Systemic infection induces conserved physiological responses that include both resistance and 'tolerance of infection' mechanisms. Temporary anorexia associated with an infection is often beneficial, reallocating energy from food foraging towards resistance to infection or depriving pathogens of nutrients. However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin (IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host's resources to maintain host-microbial interactions during pathogen-induced stress.

Development and validation of a microarray for the investigation of the CAZymes encoded by the human gut microbiome.

Distal gut bacteria play a pivotal role in the digestion of dietary polysaccharides by producing a large number of carbohydrate-active enzymes (CAZymes) that the host otherwise does not produce. We report here the design of a custom microarray that we used to spot non-redundant DNA probes for more than 6,500 genes encoding glycoside hydrolases and lyases selected from 174 reference genomes from distal gut bacteria. The custom microarray was tested and validated by the hybridization of bacterial DNA extracted from the stool samples of lean, obese and anorexic individuals. Our results suggest that a microarray-based study can detect genes from low-abundance bacteria better than metagenomic-based studies. A striking example was the finding that a gene encoding a GH6-family cellulase was present in all subjects examined, whereas metagenomic studies have consistently failed to detect this gene in both human and animal gut microbiomes. In addition, an examination of eight stool samples allowed the identification of a corresponding CAZome core containing 46 families of glycoside hydrolases and polysaccharide lyases, which suggests the functional stability of the gut microbiota despite large taxonomical variations between individuals.

Clinical features and course of bacterial meningitis in children.

AIM: To analyze the clinical features and course of and to define the risk factors for bacterial meningitis in children. MATERIAL AND METHODS: Retrospective study of 100 cases of bacterial meningitis in patients aged 0-18 years admitted to the Iasi Infectious Diseases Hospital between 2005 and 2010. RESULTS: We found a clear prevalence in male children (58%) from rural area (67%), with the highest incidence in the age group 2-5 years. A significant percentage of patients (43%) had previous hospitalization, condition which is known as predisposing factor for bacterial meningitis, the most common being ear infections (20%) and height and weight deficit (9%). 71% of patients were admitted within the first 48 h. The most common onset clinical manifestations were fever (84%), vomiting (70%), signs of meningeal irritation (59%), somnolence (23%), loss of appetite (19%), and coma in 5% of patients. In 36% of cases CSF was opalescent with moderate pleocytosis (35%); in 29% of patients CSF albumin level ranged between 0.7-1.0 g, the majority presenting normal glycorahia (71%). In only 21% of cases the microbial agent was identified (pneumococcal and meningococcal etiology, 8% and 6%, respectively). The course was generally favorable, and mortality rate was low (5%). Complications occurred in 3% of patients consisting in hydrocephalus and brain abscess. CONCLUSIONS: Bacterial meningitis remains a disease with potentially severe course. Clinical onset, most commonly atypical in children, requires differential diagnosis at the time of admission in order to initiate the most appropriate antibiotic therapy.

[Acute renal failure following Chlamydia pneumoniae pneumonia in a child]. / Insuffisance rénale aiguë consécutive à une pneumonie à Chlamydia pneumoniae chez l'enfant.

Acute renal failure (ARF) following Chlamydia pneumoniae pneumonia is rarely reported in adults. We present an observation in a 10-year-old child, who had C. pneumoniae pneumonia treated with roxithromycin for a period of 10 days, without any other nephrotoxic drug, in particular nonsteroidal anti-inflammatory drugs. At the end of antibiotic treatment, he presented with asthenia, polyuria, polydipsia, increased plasma creatinine, metabolic acidosis, hypokalemia, and markers of tubular damage. The etiological investigations showed positive C. pneumoniae antibodies, increased serum concentrations of C3 and C4 complement, IgA, and IgG. No uveitis was noted. The diagnosis was tubulointerstitial nephropathy after C. pneumoniae pneumonia. C. pneumoniae pneumonia should be considered a differential diagnosis of community-acquired pneumonia, especially in cases of poor response to conventional antibiotic therapy. It may be associated with tubulointerstitial nephropathy and/or rapidly progressive glomerulonephritis whose severity varies in children as in adults. Early and effective treatment of C. pneumoniae infection with macrolide antibiotics usually provides favorable progression of renal function.