Suitability of Hermetia illucens larvae meal and fat in broiler diets:effects on animal performance,apparent ileal digestibility,gut histology,and microbial metabolites

Background:The possibility of partially replacing soybean meal(SBM)with Hermetia illucens(HI)defatted larvae meal in broiler nutrition has frequently been suggested.For sustainability reasons,however,the larvae fat produced during defatting should also be used and could be particularly beneficial regarding gut health due to its fatty acid composition.To evaluate the suitability of HI larvae as protein and fat source,a 2×3 factorial arrangement with two types of protein,i.e.SBM(S)or SBM and 15%of its crude protein replaced by HI larvae meal(L),and three levels of fat sources,namely 0(0 L),50%(50 L)or 100%HI larvae fat(100 L)at the expense of soybean oil was applied.Results:In the starter phase,an interaction showed higher body weight(BW),average daily gain(ADG)and improved feed conversion ratio(FCR)if 50%or 100%HI larvae fat was fed with HI larvae meal.Moreover,BW,ADG and FCR improved when feeding HI larvae meal as protein source.Additionally,we observed an increased average daily feed intake in the grower,finisher,and overall phase in the L groups and an improved FCR in 0 L compared to 50 L groups during the overall period.Regarding apparent ileal digestibility,HI larvae meal feeding increased dry matter,organic matter,and fat digestibility.Feeding HI larvae meal as protein source decreased the concentrations of agmatine,spermidine,spermine and ammonia in the caecal digesta,whereas fat source affected agmatine with higher concentrations in 50 L compared to 0 L in the colonic digesta.In contrast,caecal ethanolamine concentrations increased in HI larvae meal groups compared to SBM.Caecal butyric acid concentrations decreased with HI larvae meal feeding.An interaction was found for the jejunal villus area,being higher in L+100 L compared to S+100 L.Furthermore,L groups had greater villus width.Conclusions:A partial replacement of SBM with HI larvae meal and soybean oil with HI larvae fat in broiler diets without impairing animal performance or gut health seems possible.Feeding HI larvae meal affected broiler performance positively in the starter phase and improved apparent ileal digestibility.

Fecal scores and microbial metabolites in weaned piglets fed different protein sources and levels

This experiment studied the effects of dietary protein sources and levels on the gut health of piglets,p H value,and concentrations of microbial metabolites(ammonia-N,volatile fatty acids [VFA],and polyamines) in the distal colonic and proximal colonic digesta of piglets weaned at 21 d of age.A total of 150 early-weaned piglets were allotted randomly to 5 diets: 1) control diet(CT; 17% CP),2) CT formulated with more soy protein concentrate(SPC19; 19% CP),3) more fish meal(FM19; 19% CP),4) CT formulated with more soy protein concentrate(SPC23; 23% CP),and 5) more fish meal(FM23; 23%CP).Results showed high protein level increased fecal score(P < 0.05),but different protein sources did not(P > 0.05).The p H value and ammonia-N concentration of digesta in the proximal and distal colon of FM23 were significantly higher(P < 0.05) than those of CT.Acetic acid,propionic acid,butyric acid and valeric acid concentrations in the proximal colon of FM23 exceeded those of CT,SPC19,and FM19(P < 0.05);however,isobutyric acid and isovaleric acid were not affected(P > 0.05).Histamine and spermidine concentrations of FM23 were higher than those of other treatments(P < 0.05).Propionic acid and butyric acid concentrations in the distal colon were higher of FM23 than of FM19(P < 0.05); putrescine,histamine and spermidine were higher of FM23 than of LP and FM19(P < 0.05).It was concluded that high dietary CP content increased microbial metabolites(ammonia-N,histamine,putrescine) in colonic digesta and aggravated piglets' diarrhea.

Mesenteric lymph system constitutes the second route in gut-liver axis and transports metabolism-modulating gut microbial metabolites

The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Intestinal flora: New perspective of type 2 diabetes

Diabetes comprises a group of metabolic diseases characterized by hyperglycemia stemming from various factors.Current diabetes management primarily focuses on blood glucose control,yet it is inherently progressive,necessitating increased reliance on exogenous blood glucose control methods over time.Therefore,there is an urgent need to explore novel intervention strategies addressing both diabetes and its complications.The human intestinal microbiota,often referred to as the"second genome",exhibits significant diversity and plays a pivotal role in insulin resistance,glucose and lipid metabolism,and inflammatory response.Notably,Li and Guo have elucidated the involvement of intestinal flora in the pathogenesis of type 2 diabetes mellitus(T2DM)and proposed a novel therapeutic approach targeting intestinal microbes.This advancement enhances our comprehension of the multifaceted and multi-target regulation of T2DM by intestinal microflora,thereby offering fresh avenues for understanding its pathogenesis and clinical management.This letter briefly summarizes the role of intestinal flora in T2DM based on findings from animal experiments and clinical studies.Additionally,it discusses the potential clinical applications and challenges associated with targeting intestinal flora as therapeutic interventions.

Role of metabolites derived from gut microbiota in inflammatory bowel disease

Over the past two decades,it is improved gut microbiota plays an important role in the health and disease pathogenesis.Metabolites,small molecules produced as intermediate or end products of microbial metabolism,is considered as one of the major interaction way for gut microbiota with the host.Bacterial metabolisms of dietary substrates,modification of host molecules or bacteria are the major source of metabolites.Signals from microbial metabolites affect immune maturation and homeostasis,host energy metabolism as well as mucosal integrity maintenance.Based on many researches,the composition and function of the microbiota can be changed,which is also seen in the metabolite profiles of patients with inflammatory bowel disease(IBD).Additionally,some specific classes of metabolites also can trigger IBD.In this paper,definition of the key classes of microbialderived metabolites which are changed in IBD,description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut microbiota.An important next step is to elucidate a human-relevant"map"of microbiota-host interactions that regulate the metabolic health of the host.An improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat obesity.Intestinal mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions,including cancer,neurodegeneration,and aging.The mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly understood.Understanding the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier breakage.Changes in the composition and function of the gut microbiota,i.e.,dysbiosis,are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier dysfunction.Many effects of the microbiota on the host are mediated by microbiota-derived metabolites.In this review,we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic diseases.The design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.

Microbiome-liver crosstalk:A multihit therapeutic target for liver disease

Liver disease has become a leading cause of death,particularly in the West,where it is attributed to more than two million deaths annually.The correlation between gut microbiota and liver disease is still not fully understood.However,it is well known that gut dysbiosis accompanied by a leaky gut causes an increase in lipopolysaccharides in circulation,which in turn evoke massive hepatic inflammation promoting liver cirrhosis.Microbial dysbiosis also leads to poor bile acid metabolism and low short-chain fatty acids,all of which exacerbate the inflammatory response of liver cells.Gut microbial homeostasis is maintained through intricate processes that ensure that commensal microbes adapt to the low oxygen potential of the gut and that they rapidly occupy all the intestinal niches,thus outcompeting any potential pathogens for available nutrients.The crosstalk between the gut microbiota and its metabolites also guarantee an intact gut barrier.These processes that protect against destabilization of gut microbes by potential entry of pathogenic bacteria are collectively called colonization resistance and are equally essential for liver health.In this review,we shall investigate how the mechanisms of colonization resistance influence the liver in health and disease and the microbial-liver crosstalk potential as therapeutic target areas.

Gut microbiome:New perspectives for type 2 diabetes prevention and treatment

Type 2 diabetes mellitus(T2DM),which is distinguished by increased glucose levels in the bloodstream,is a metabolic disease with a rapidly increasing incidence worldwide.Nevertheless,the etiology and characteristics of the mechanism of T2DM remain unclear.Recently,abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM.The gut microbiome,the largest microecosystem,engages in material and energy metabolism in the human body.In this review,we concentrated on the correlation between the gut flora and T2DM.Meanwhile,we summarized the pathogenesis involving the intestinal flora in T2DM,as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM.Through the analysis presented here,we draw attention to further exploration of these research directions.

Regulation of serotonin production by specific microbes from piglet gut

Background Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut.Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models.However,how gut microbes regulate intestinal serotonin production in piglets remains vague.To investigate the relationship between microbiota and serotonin specifically in the colon,microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion.Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investi-gate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells.Results Antibiotic infusion increased quantities of Lactobacillus amylovorus(LA)that positively correlated with increased serotonin concentrations in the colon,while no effects observed for Limosilactobacillus reuteri(LR).To understand how microbes regulate serotonin,representative strains of LA,LR,and Streptococcus alactolyticus(SA,enriched in feces from prior observation)were selected for cell culture studies.Compared to the control group,LA,LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1(TPH1)expression and promoted serotonin production in IPEC-J2 cells,while in RIN-14B cells only LA exerted similar action.To investigate potential mechanisms mediated by microbe-derived molecules,microbial metabolites including lactate,acetate,glutamine,andγ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacte-rial supernatant.Among these metabolites,acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1.Similar effects were also recapitulated when treating the cells with AR420626,an agonist targeting free fatty acid receptor 3.Conclusions Overall,these results suggest that Lactobacillus amylovorus showed a positive correlation with sero-tonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures.These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host,which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.

The role of gut microbiota associated metabolites in digestive disorders

The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

Over-feeding the gut microbiome: A scoping review on health implications and therapeutic perspectives

The human gut microbiome has gained increasing attention over the past two decades.Several findings have shown that this complex and dynamic microbial ecosystem can contribute to the maintenance of host health or,when subject to imbalances,to the pathogenesis of various enteric and non-enteric diseases.This scoping review summarizes the current knowledge on how the gut microbiota and microbially-derived compounds affect host metabolism,especially in the context of obesity and related disorders.Examples of microbiome-based targeted intervention strategies that aim to restore and maintain an eubiotic layout are then discussed.Adjuvant therapeutic interventions to alleviate obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics,probiotics and synbiotics.However,these approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem,making the development of innovative and tailored microbiome-based intervention strategies of utmost importance in clinical practice.In this regard,the administration of next-generation probiotics and engineered microbiomes has shown promising results,together with more radical intervention strategies based on the replacement of the dysbiotic ecosystem by means of fecal microbiota transplantation from healthy donors or with the introduction of synthetic communities specifically designed to achieve the desired therapeutic outcome.Finally,we provide a perspective for future translational investigations through the implementation of bioinformatics approaches,including machine and deep learning,to predict health risks and therapeutic outcomes.

Effects of vegetarian diet-associated nutrients on gut microbiota and intestinal physiology

People are increasingly aware of the role of vegetarian diets in modulating human gut microbial abundance and intestinal physiology.A plant-based diet is thought to benefit host health by contributing to establish a diverse and stable microbiome.In addition,microbe-derived metabolites of specific nutrients known to be abundant in vegetarian diets(such as indigestible carbohydrates,arginine,and others) are important to promote effective intestinal immune responses,maintain intestinal barrier function,and protect against pathogens.This review explores the characteristics of the gut microbiome formed by vegetarian diets and the effects of diet-associated nutrients on intestinal microbial abundance.The interactions between the microbe-derived metabolites of vegetarian diet-associated nutrients and intestinal physiology are also discussed.

Relationship Between Short-chain Fatty Acids and Parkinson’s Disease:A Review from Pathology to Clinic

Parkinson’s disease(PD)is a complicated neurodegenerative disease,characterized by the accumulation ofα-synuclein(α-syn)in Lewy bodies and neurites,and massive loss of midbrain dopamine neurons.Increasing evidence suggests that gut microbiota and microbial metabolites are involved in the development of PD.Among these,short-chain fatty acids(SCFAs),the most abundant microbial metabolites,have been proven to play a key role in brain-gut communication.In this review,we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor symptoms.Future research should focus on further elucidating the role of SCFAs in neuroinflammation,as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners:A metabolic and bacteriological investigation in Escherichia coli

Incomplete separation and recycling of nanoparticles are causing undesirable nanopollution and thus raising great concerns with regard to nanosafety.Since microorganisms are important regulator of physiological processes in many organisms,the interaction between nanopollution and microbial metabolomics and the resultant impact on the host’s health are important but unclear.To investigate how typical nanopollution perturbs microbial growth and metabolism,Escherichia coli(E.coli)in vitro was treated with six water-dispersible nanomaterials(nanoplastic,nanosilver,nano-TiO 2,nano-ZnO,semiconductor quantum dots(QDs),carbon dots(CDs))at human-/environment-relevant concentration levels.The nanomaterials exhibited type-specific toxic effects on E.coli growth.Global metabolite profiling was used to characterize metabolic disruption patterns in the model microorganism exposed to different nanopollutants.The percentage of significant metabolites(p<0.05,VIP>1)accounted for 6%–38%of the total 293 identified metabolites in each of the nanomaterial-contaminated bacterial groups.Metabolic results also exhibited significant differences between different nanopollutants and dose levels,revealing type-specific and untypical concentration-dependent metabolic responses.Key metabolites responsive to nanopollution exposures were mainly involved in amino acid and purine metabolisms,where 5,4,and 7 significant metabolic features were included in arginine and proline metabolism,phenylalanine metabolism,and purine metabolism,respectively.In conclusion,this study horizontally compared and demonstrated how typical nanopollution perturbs microbial growth and metabolomics in a type-specific manner,which broadens our understanding of the ecotoxicity of nanopollutants on microorganisms.

Human Gut Microbiota and Gastrointestinal Cancer

Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also inter- fere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influ- ence of gut microbiota on cancers in the gastrointestinal （GI） tract （including esophageal, gastric, colorectal, liver, and pancreatic cancers） and the regulation of microbiota by diet, prebiotics, pro- biotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.

Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids

A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.

Discovery of new hazimycin congeners from Kitasatospora sp.P07101

In an analytical study of microbial broths,the actinomycete strain Kitasatospora sp.P07101 was found to produce three new congeners,which were designated hazimycins B(1),C(2),and D(3),together with the previously reported hazimycin(renamed hazimycin A(4)).The structures of these hazimycins were examined using various spectroscopic methods including nuclear magnetic resonance(NMR),and the results revealed that 1–3 were analogues of hazimycin with the replacement of one of the two isonitrile groups in 4 by an NH-formyl group in 1,the two isonitrile groups and an amide group by two NH-formyl groups and a nitrile group in 2,and the two isonitrile groups and two amide groups by two NH-formyl groups and two nitrile groups in 3.Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive bacteria and Candida albicans.These results indicated that the presence of two isonitrile groups in the hazimycin structure is essential for antimicrobial activity.

Indoor microbiome and allergic diseases:From theoretical advances to prevention strategies

The prevalence of allergic diseases,such as asthma,rhinitis,eczema,and sick building syndrome(SBS),has increased drastically in the past few decades.Current medications can only relieve the symptoms but not cure these diseases whose development is suggested to be greatly impacted by the indoor microbiome.However,no study comprehensively summarizes the progress and general rules in the field,impeding subsequent translational application.To close knowledge gaps between theoretical research and practical application,we conducted a comprehensive literature review to summarize the epidemiological,environmental,and molecular evidence of indoor microbiome studies.Epidemiological evidence shows that the potential protective indoor microorganisms for asthma are mainly from the phyla Actinobacteria and Proteobacteria,and the risk microorganisms are mainly from Bacilli,Clostridia,and Bacteroidia.Due to extremely high microbial diversity and geographic variation,different health-associated species/genera are detected in different regions.Compared with indoor microbial composition,indoor metabolites show more consistent associations with health,including microbial volatile organic compounds(MVOCs),lipopolysaccharides(LPS),indole derivatives,and flavonoids.Therefore,indoor metabolites could be a better indicator than indoor microbial taxa for environmental assessments and health outcome prediction.The interaction between the indoor microbiome and environmental characteristics(surrounding greenness,relative humidity,building confinement,and CO_(2) concentration)and immunology effects of indoor microorganisms(inflammatory cytokines and pattern recognition receptors)are briefly reviewed to provide new insights for disease prevention and treatment.Widely used tools in indoor microbiome studies are introduced to facilitate standard practice and the precise identification of health-related targets.