Continuous intake of galacto-oligosaccharides containing syrup contributes to maintaining the health of household dogs by modulating their gut microbiota.

Interest is growing in the relationship of the microbiota and intestinal environment with health in companion animals. Galacto-oligosaccharides (GOS), typical prebiotics, are expected to provide benefits in dogs. Previous studies of GOS in dogs have involved dogs with similar rearing conditions and diets, which may have biased the results. We conducted an open study of 26 healthy dogs kept in households with diverse rearing environments in order to evaluate how the intake of a GOS-containing syrup affects the intestinal microbiota and its metabolites. Each dog was fed 1.2-4.8 g of the GOS-containing syrup (GOS 0.5-2.0 g equivalent) for 8 weeks. Fecal microbiota, fecal concentrations of organic acids and putrefactive products, fecal odor, and serum uremic toxin concentrations were evaluated before intake (0 weeks), during the 8-week intake period (4 and 8 weeks), and 4 weeks after intake (12 weeks). The activity of N-benzoyl-DL-arginine peptidase in dental plaque, which may be associated with periodontal disease, was evaluated at 0 and 8 weeks. Continuous intake of GOS resulted in changes in fecal microbiota, with a particularly marked increase in the abundance of Megamonas, which produces propionic acid. Other findings included a significant increase in the fecal acetic, propionic, and n-butyric acid concentrations. Additionally, significant decreases in fecal odor, fecal phenol concentration, and serum indoxyl sulfate concentration. Intake of GOS was also associated with a significant decrease in N-benzoyl-DL-arginine peptidase activity in dental plaques. These results suggest that continuous intake of GOS may contribute to canine health.

Effects of Botulinum Toxin-A for Spasticity and Nociceptive Pain in Individuals with Spinal Cord Injury: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.

Nutritional compounds and risk assessment of mycotoxins in ecological and conventional nuts.

This comprehensive study aimed to determine the level of nutritional compounds (20 amino acids, 11 phenolic acids, and 8 vitamins) and hazard compounds (14 mycotoxins) in ten types of conventional and ecological nuts from 25 countries. Moreover, chronic and acute toxicological risk assessment of mycotoxins was performed. Examined constituents were determined using LC-MS/MS. Ecological pine nuts showed the highest level of amino acids (233.87 g kg-1) compared to conventional (207 g kg-1), pecans-phenolic acids (816.6 mg kg-1 in ecological and 761 mg kg-1 in conventional), while pistachios-vitamins (3471.4 mg kg-1 in ecological and 3098.4 mg kg-1 in conventional). Increased concentration of mycotoxins was determined in conventional peanuts (54 µg kg-1) and walnuts (49.9 µg kg-1). Children were the most exposed population to acute intoxication with HT-2 toxin in conventional pistachios (20.66% ARfD). The results confirmed the nutritional importance of ecological nuts and emphasized the need for continuous screening of mycotoxins.

First report of PST-producing Microseira wollei from China reveals its novel toxin profile.

Microseira wollei, a globally distributed freshwater bloom-forming benthic cyanobacterium, is known for its production of cyanotoxins and taste and odor (T&O). While CYN (Cylindrospermopsin)-producing populations of M. wollei are confined to Australia, PST (Paralytic shellfish toxins)-producing populations have been exclusively documented in North America. In this study, four benthic cyanobacterial strains, isolated from West Lake in China, were identified as M. wollei based on morphological and phylogenetic analyses. Detection of sxtA gene and UPLC-MS/MS analysis conclusively confirmed the PST-producing capability of M. wollei CHAB5998. In the phylogenetic tree of 16S rDNA, M. wollei strains formed a monophyletic group with two subclades. Notably, non-PST-producing Chinese strains clustered with Australian strains in Clade II, while all other strains, including PST-producing ones, clustered in Clade I. Additionally, CHAB5998 contains ten PST variants, of which STX, NEO, GTX2, GTX3, GTX5 and C1 were identified for the first time in M. wollei. Sequence analysis of PST biosynthetic gene cluster (sxt) genes indicated potential base variations, gene rearrangements, insertions, and deletions in the strain CHAB5998. Also, sxt gene has a longer evolutionary history in M. wollei than that in cyanobacteria from Nostocales. Multiple recombination breakpoints detected in sxt genes and the inconsistency in the topology of the phylogenetic trees between sxt and 16S rDNA suggested that multiple horizontal gene transfers (HGT) have occurred. Overall, the present study marks the first documented occurrence of PST-producing M. wollei outside of North America and identifies it as the first toxic freshwater benthic cyanobacterium in China. This revelation implies that benthic cyanobacteria may pose a higher environmental risk in China than previously acknowledged.

Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications.

Several species during evolution suffered random mutations in response to various environmental factors, which resulted in the formation of venom in phylogenetically distant species. The composition of the venom of most species is poorly known. Snake venom is well characterized while most species have poorly known composition. In contrast, snake venoms are well characterized which proteins and peptides are the main active and most abundant constituents. 42 protein families have been identified, including metalloproteins known as metalloproteinases. These macromolecules are enzymes with zinc in their active site derived from the disintegrin A and metalloproteinase (ADAM) cellular family and are categorized into three classes (PI, PII and PIII) according to their domain organization. The snake venom metalloproteinases (SVMP) are cytotoxic, neurotoxic, myotoxic and/or hematotoxic with a crucial role in the defense and restraint of prey. In this scenario envenoming represents a danger to human health and has been considered a neglected disease worldwide, particularly in tropical and subtropical countries. Nevertheless, recently advances in "omics" technologies have demonstrated interesting biological activities of SVMPs such as antimicrobial, anticancer, against cardiovascular diseases and nervous system disorders. Metalloproteins have the therapeutic potential to be converted into drugs as other components of the venom have undergone this process (e.g., captopril, tirefiban and eptifibatide). So, this chapter is focused on the metalloproteins found in the secretions of venomous species, highlight some aspects such as structure, biological activity, pharmacological therapeutic potential and on.

Insoluble polysaccharides produced in plant cell cultures protect from Clostridioides difficile colitis.

Clostridioides difficile infection (CDI) poses a significant health threat due to high recurrence rates. Antimicrobial agents are commonly used to manage CDI-related diarrhoea; however, by aggravating intestinal dysbiosis, antibiotics enable C. difficile spores germination and production of toxins, the main virulence factors. Therefore, the binding of exotoxins using adsorbents represents an attractive alternative medication for the prevention and treatment of relapses. In this study, we provided evidence that the natural insoluble polysaccharides, named ABR119, extracted by plant cell cultures, effectively trap C. difficile toxins. In our experiments, ABR119 exhibited no cytotoxicity in vitro and was safely administered in vivo. In the animal model of C. difficile-associated colitis, ABR119 (50 mg/kg body weight) significantly reduced the colonic myeloperoxidase activity and severity of inflammation, preventing body weight loss. These effects were not evident when we treated animals with wheat bran polysaccharides. We did not detect bacterial killing effects of ABR119 against C. difficile nor against bacterial species of the normal gut microbiota. Moreover, ABR119 did not interfere in vitro with the antimicrobial activities of most clinically used antibiotics. In summary, ABR119 holds promise for treating and preventing C. difficile colitis by trapping the bacterial toxins, warranting further studies to assess the ABR119 potential in human infections caused by C. difficile.

Molluscs toxin peptides in cardiovascular disease management.

This letter emphasizes the potential of mollusc toxin peptides as innovative treatments for cardiovascular diseases (CVDs). Given the rising incidence of CVDs and the limitations of current therapies, new approaches are essential. Molluscs produce bioactive peptides that show promising anti-hypertensive, anti-thrombotic, and cardio-protective properties. For example, conotoxins from marine snails inhibit voltage-gated calcium channels, indicating their potential as anti-hypertensive agents. Advancements in peptide engineering can address challenges related to bioavailability and stability. Increased research and collaboration are needed to investigate these peptides' mechanisms, therapeutic potential, and safety, which could lead to groundbreaking CVD treatments.

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Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.

Spatial distribution of lipophilic shellfish toxins in seawater and sediment in the Bohai Sea and the Yellow Sea, China.

Lipophilic shellfish toxins (LSTs) are widely distributed in marine environments worldwide, potentially threatening marine ecosystem health and aquaculture safety. In this study, two large-scale cruises were conducted in the Bohai Sea and the Yellow Sea, China, in spring and summer 2023 to clarify the composition, concentration, and spatial distribution of LSTs in the water columns and sediments. Results showed that okadaic acid (OA), dinophysistoxin-1 (DTX1) and/or pectenotoxin-2 (PTX2) were detected in 249 seawater samples collected in spring and summer. The concentrations of ∑LSTs in seawater were ranging of ND (not detected) -13.86, 1.60-17.03, 2.73-17.39, and 1.26-30.21 pmol L-1 in the spring surface, intermediate, bottom water columns and summer surface water layers, respectively. The detection rates of LSTs in spring and summer seawater samples were 97% and 100%, respectively. The high concentrations of ∑LSTs were mainly distributed in the north Yellow Sea and the northeast Bohai Sea in spring, and in the northeast Yellow Sea, the waters around Laizhou Bay and Rongcheng Bay in summer. Similarly, only OA, DTX1 and PTX2 were detected in the surface sediments. Overall, the concentration of ∑LSTs in the surface sediments of the northern Yellow Sea was higher than that in other regions. In sediment cores, PTX2 was mainly detected in the upper sediment samples, whereas OA and DTX1 were detected in deeper sediments, and LSTs can persist in the sediments for a long time. Overall, OA, DTX1 and PTX2 were widely distributed in the water column and surface sediments in the Bohai Sea and the Yellow Sea, China. The results of this study contribute to the understanding of spatial distribution of LSTs in seawater and sediment environmental media and provide basic information for health risk assessment of phycotoxins.

Venom gland organogenesis in the common house spider.

Venom is a remarkable innovation found across the animal kingdom, yet the evolutionary origins of venom systems in various groups, including spiders, remain enigmatic. Here, we investigated the organogenesis of the venom apparatus in the common house spider, Parasteatoda tepidariorum. The venom apparatus consists of a pair of secretory glands, each connected to an opening at the fang tip by a duct that runs through the chelicerae. We performed bulk RNA-seq to identify venom gland-specific markers and assayed their expression using RNA in situ hybridisation experiments on whole-mount time-series. These revealed that the gland primordium emerges during embryonic stage 13 at the chelicera tip, progresses proximally by the end of embryonic development and extends into the prosoma post-eclosion. The initiation of expression of an important toxin component in late postembryos marks the activation of venom-secreting cells. Our selected markers also exhibited distinct expression patterns in adult venom glands: sage and the toxin marker were expressed in the secretory epithelium, forkhead and sum-1 in the surrounding muscle layer, while Distal-less was predominantly expressed at the gland extremities. Our study provides the first comprehensive analysis of venom gland morphogenesis in spiders, offering key insights into their evolution and development.

Clostridium perfringens in central Colombia: frequency, toxin genes, and risk factors.

Clostridium perfringens is an opportunistic bacterium that causes intestinal diseases in both humans and animals. This study aimed to assess the frequency of C. perfringens and the presence of toxin-encoding genes in fecal samples from individuals with or without gastrointestinal symptoms in the Department of Boyacá, Colombia. Additionally, risk factors associated with carriage and disease development were analyzed. A total of 114 stool samples were analyzed using a molecular test based on specific polymerase chain reaction (PCR) targeting 16S-rRNA and alpha toxin (cpa) genes. For individuals with a positive result for the PCR test, stool samples were cultured on Tryptose Sulfite Cycloserine (TSC) agar. Two to five colonies forming units were selected based on phenotypic characteristics, resulting in 56 bacterial isolates. These isolates were then analyzed for toxin-coding genes associated with gastrointestinal diseases. In addition, sociodemographic and clinical data from 77 individuals were also analyzed. The overall frequency of C. perfringens was 19.3% (n = 22/114). The detection frequency in 77 individuals with clinical data was 16.6% (n = 5/30) among symptomatic individuals and 21.2% (n = 10/47) among asymptomatic individuals. All 56 isolates obtained carried the cpa gene, while cpb2 was present in 10.7% (n = 6/56); cpe and cpb genes were not detected. Notably, diabetes and autoimmune diseases are significantly associated with an increased risk of C. perfringens detection (adjusted OR 8.41: 95% CI 1.32-35.89). This study highlights an elevated frequency of C. perfringens and the presence of the cpb2 gene in asymptomatic individuals compared with their symptomatic counterparts. These findings offer insights into the distribution and virulence factors of C. perfringens at a micro-geographical level. This information supports the need for developing tailored prevention strategies based on local characteristics to promote active surveillance programs based on molecular epidemiology.

Effects of the toxic dinoflagellate, Alexandrium pacificum, on the marine diatom, Chaetoceros muelleri, and mussel (Perna canaliculus) sperm and hemocytes.

Harmful algal blooms (HABs) of Alexandrium pacificum have affected the Marlborough Sounds in New Zealand since 2010, posing a threat to green-lipped mussel (GLM, Perna canaliculus) farming. Previous studies have shown A. pacificum has negative effects GLM embryos and larvae. To further investigate these toxic mechanisms, in vitro bioassays were conducted on GLM spermatozoa, hemocytes, and the diatom, Chaetoceros muelleri. The three cell types were exposed to several treatments of A. pacificum for 2 h and responses were measured using flow cytometry and pulse amplitude-modulated fluorometry. Significant spermatozoa mortality was recorded in treatments containing A. pacificum cells or fragments, while hemocyte and C. muelleri mortality was recorded in cell-free treatments of A. pacificum which contained paralytic shellfish toxins (PSTs). Variation in sensitivity between cell types as well as the sublethal effects observed, emphasise the diverse toxic mechanisms of A. pacificum on co-occurring species in the environment.

Bio-derived carbon-based materials for sustainable environmental remediation and wastewater treatment.

Biosynthesized nanocomposites, particularly those incorporating carbon-based materials, exhibit exceptional tunability and multifunctionality, surpassing the capabilities of conventional materials in these aspects. Developing practical solutions is critical to address environmental toxins from pharmaceuticals, heavy metals, pesticides, and dyes. Biomass waste is a readily available carbon source, which emerges as a promising material for producing biochar due to its inherent advantages: abundance, low cost, and environmentally friendly nature. This distribution mainly uses carbon-based materials (CBMs) and biomass waste in wastewater treatment. This review paper investigates several CBM types, including carbon aerogels, nanotubes, graphene, and activated carbon. The development of bio-derived carbon-based nanomaterials are discussed, along with the properties and composition of carbon materials derived from biomass waste and various cycles, such as photodegradation, adsorption, and high-level oxidation processes for natural remediation. In conclusion, this review examines the challenges associated with biochar utilization, including cost, recovery, and practical implementation.

Initiation of H1-T6SS dueling between Pseudomonas aeruginosa.

The Type VI secretion system (T6SS) is a multicomponent apparatus, present in many Gram-negative bacteria, which can inhibit bacterial prey in various ecological niches. Pseudomonas aeruginosa assembles one of its three T6SS (H1-T6SS) to respond to attacks from adjacent competing bacteria. Surprisingly, repeated assemblies of the H1-T6SS, termed dueling, were described in a monoculture in the absence of an attacker strain; however, the underlying mechanism was unknown. Here, we explored the role of H2-T6SS of P. aeruginosa in triggering H1-T6SS assembly. We show that H2-T6SS inactivation in P. aeruginosa causes a significant reduction in H1-T6SS dueling and that H2-T6SS activity directly triggers retaliation by the H1-T6SS. Intraspecific competition experiments revealed that elimination of H2-T6SS in non-immune prey cells conferred protection from H1-T6SS. Moreover, we show that the H1-T6SS response is triggered independently of the characterized lipase effectors of the H2-T6SS, as well as those of Acinetobacter baylyi and Vibrio cholerae. Our results suggest that H1-T6SS response to H2-T6SS in P. aeruginosa can impact intraspecific competition, particularly when the H1-T6SS effector-immunity pairs differ between strains, and could determine the outcome of multistrain colonization.IMPORTANCEThe opportunistic pathogen Pseudomonas aeruginosa harbors three different Type VI secretion systems (H1, H2, and H3-T6SS), which can translocate toxins that can inhibit bacterial competitors or inflict damage to eukaryotic host cells. Unlike the unregulated T6SS assembly in other Gram-negative bacteria, the H1-T6SS in P. aeruginosa is precisely assembled as a response to various cell damaging attacks from neighboring bacterial cells. Surprisingly, it was observed that neighboring P. aeruginosa cells repeatedly assemble their H1-T6SS toward each other. Mechanisms triggering this "dueling" behavior between sister cells were unknown. In this report, we used a combination of microscopy, genetic and intraspecific competition experiments to show that H2-T6SS initiates H1-T6SS dueling. Our study highlights the interplay between different T6SS clusters in P. aeruginosa, which may influence the outcomes of multistrain competition in various ecological settings such as biofilm formation and colonization of cystic fibrosis lungs.

Novel single-entry point injection technique for masseter hypertrophy treatment using botulinum neurotoxin based on patient-reported comfort.

INTRODUCTION: Botulinum neurotoxin (BoNT) injections are widely used for the treatment of masseter muscle hypertrophy in Southeast Asia. However, there remains a lack of consensus regarding the optimal injection technique. This study aimed to compare the efficacy and patient discomfort associated with single-entry point injections versus multiple three-point injections for masseter muscle hypertrophy treatment with BoNT. MATERIALS AND METHODS: Sixteen participants, comprising both male and female Korean adults aged 22-63, were enrolled in the study. On the left side of the face, single-entry point injections were administered, followed by multidirectional injections, while on the right side, three-point injections were given. Pain intensity during the procedure was assessed using visual analogue scale scores. RESULT: Our results revealed that participants experienced lower levels of pain with single-entry point injections compared to three-point injections (average visual analogue scores of 3.31 and 5.19, respectively). CONCLUSION: These findings highlight the potential benefits of single-entry point injections in reducing patient discomfort during masseter muscle hypertrophy treatment with BoNT. We advocate for further research to validate these findings and encourage practitioners to consider single-entry point injections as a viable option for enhancing treatment outcomes in their clinical practice.

The Degradation of Botulinum Neurotoxin Light Chains Using PROTACs.

Botulinum neurotoxins are some of the most potent natural toxins known; they cause flaccid paralysis by inhibiting synaptic vesicle release. Some serotypes, notably serotype A and B, can cause persistent paralysis lasting for several months. Because of their potency and persistence, botulinum neurotoxins are now used to manage several clinical conditions, and there is interest in expanding their clinical applications using engineered toxins with novel substrate specificities. It will also be beneficial to engineer toxins with tunable persistence. We have investigated the potential use of small-molecule proteolysis-targeting chimeras (PROTACs) to vary the persistence of modified recombinant botulinum neurotoxins. We also describe a complementary approach that has potential relevance for botulism treatment. This second approach uses a camelid heavy chain antibody directed against botulinum neurotoxin that is modified to bind the PROTAC. These strategies provide proof of principle for the use of two different approaches to fine tune the persistence of botulinum neurotoxins by selectively targeting their catalytic light chains for proteasomal degradation.

State-of-the-art-review Mechanisms of action of SGLT2 inhibitors and clinical implications.

Inhibitors of the Na+-coupled glucose transporter SGLT2 (SGLT2i) primarily shift the reabsorption of large amounts of glucose from the kidney's early proximal tubule to downstream tubular segments expressing SGLT1, and the non-reabsorbed glucose is spilled into the urine together with some osmotic diuresis. How can this protect the kidneys and heart from failing as observed in individuals with and without type 2 diabetes? Mediation analyses identified clinical phenotypes of SGLT2i associated with improved kidney and heart outcome, including a reduction of plasma volume or increase in hematocrit, and lowering of serum urate levels and albuminuria. This review outlines how primary effects of SGLT2i on the early proximal tubule can explain these phenotypes. The physiology of tubule-glomerular communication provides the basis for acute lowering of GFR and glomerular capillary pressure, which contributes to lowering of albuminuria but also to long term preservation of GFR, at least in part by reducing kidney cortex oxygen demand. Functional co-regulation of SGLT2 with other sodium and metabolite transporters in the early proximal tubule explains why SGLT2i initially excrete more sodium than expected and are uricosuric, thereby reducing plasma volume and serum urate. Inhibition of SGLT2 reduces early proximal tubule gluco-toxicity and by shifting transport downstream may simulate "systemic hypoxia", and the resulting increase in erythropoiesis, together with the osmotic diuresis, enhances hematocrit and improves blood oxygen delivery. Cardio-renal protection by SGLT2i is also provided by a fasting-like and insulin-sparing metabolic phenotype and, potentially, by off-target effects on the heart and microbiotic formation of uremic toxins.

Transcriptome response of a marine copepod in response to environmentally-relevant concentrations of saxitoxin.

Paralytic shellfish toxins (PSTs) can pose a serious threat to human health. Among them, saxitoxin (STX) is one of the most potent natural neurotoxins. Here, the copepod Tigriopus japonicus, was exposed to environmentally relevant concentrations (2.5 and 25 µg/L) STX for 48 h. Although no lethal effects were observed at both concentrations, the transcriptome was significantly altered, and displayed a concentration-dependent response. STX exposure decreased the copepod's metabolism and compromised immune defense and detoxification. Additionally, STX disturbed signal transduction, which might affect other cellular processes. STX exposure could inhibit the copepod's chitin metabolism, disrupting its molting process. Also, the processes related to damage repair and protection were up-regulated to fight against high concentration exposure. Collectively, this study has provided an early warning of PSTs for coastal ecosystem not only because of their potent toxicity effect but also their bioaccumulation that can transfer up the food chain after ingestion by copepods.

Fragment Screening to Identify Inhibitors Targeting Ribosome Binding of Shiga Toxin 2.

Shiga toxins are the main virulence factors of Shiga toxin producing E. coli (STEC) and S. dysenteriae. There is no effective therapy to counter the disease caused by these toxins. The A1 subunits of Shiga toxins bind the C-termini of ribosomal P-stalk proteins to depurinate the sarcin/ricin loop. The ribosome binding site of Shiga toxin 2 has not been targeted by small molecules. We screened a fragment library against the A1 subunit of Shiga toxin 2 (Stx2A1) and identified a fragment, BTB13086, which bound at the ribosome binding site and mimicked the binding mode of the P-stalk proteins. We synthesized analogs of BTB13086 and identified a series of molecules with similar affinity and inhibitory activity. These are the first compounds that bind at the ribosome binding site of Stx2A1 and inhibit activity. These compounds hold great promise for further inhibitor development against STEC infection.

Mitigation Strategies against Food Safety Contaminant Transmission from Black Soldier Fly Larva Bioconversion.

The black soldier fly larva, Hermetia illucens, can efficiently convert organic waste into biomatter for use in animal feed. This circularity comes with a risk of contaminating downstream consumers of the larval products with microbes, heavy metals, and other hazards potentially present in the initial substrate. This review examines research on mitigation techniques to manage these contaminants, from pretreatment of the substrate to post-treatment of the larvae. While much research has been done on such techniques, little of it focused on their effects on food safety contaminants. Cheap and low-technology heat treatment can reduce substrate and larval microbial load. Emptying the larval gut through starvation is understudied but promising. Black soldier fly larvae accumulate certain heavy metals like cadmium, and their ability to process certain hazards is unknown, which is why some government authorities are erring on the side of caution regarding how larval bioconversion can be used within feed production. Different substrates have different risks and some mitigation strategies may affect larval rearing performance and the final products negatively, so different producers will need to choose the right strategy for their system to balance cost-effectiveness with sustainability and safety.