Effect of glyphosate on intestine in fish: a review

Glyphosate (also known as N-(phosphonomethyl) glycine) was introduced to the market as a herbicide back in 1972, but it is now one of the most widely used herbicides globally (Kaliannan et al., 2002). Glyphosate has been advertised as having a wide variety of uses based on its affordability along with its combination of broad-spectrum abuse with respect to the various types of weeds being controlled. Glyphosate may be used in a variety of different commercial formulations, with one such formulation being Roundup®; these formulations can be used for various purposes including agricultural, horticultural and municipal use. The widespread use of glyphosate has resulted in it becoming one of the most widely used herbicides globally, and because of this, many environmental concerns have arose. These concerns have primarily been focused on the persistence of glyphosate in the environment and its potential to pollute freshwater ecosystems. Aquatic organisms such as naturally occurring marine fish, including some economically important species such as bony fish (e.g., African catfish), have a high likelihood of being exposed to glyphosate through contamination of rivers, ponds and agricultural runoff (Erhunmwunse et al. , 2014; Rad et al. , 2022). Bony fish are adaptable, omnivorous fish species that are native to Africa's freshwater systems and have become popular in aquaculture as they can adapt to various environments, grow quickly and provide a large volume of protein. Furthermore, due to the fish being physiologically sensitive to waterborne contaminants, bony fish are commonly used as experimental animals when conducting ecotoxicology studies (Sabra and Mehana 2015). Among the many effects that toxicants can have on physiological systems, the gastro-intestinal tract is especially sensitive to these toxicants because the gastro-intestinal tract is the first point of entry into the animal’s body through which nutrients from food can be absorbed and digested. The gastro-intestinal tract is also responsible for providing the animal with an immune response to pathogens and allows for a symbiotic relationship to develop between the host organism and its microbes. Exposure of aquatic organisms to the detoxicant glyphosate can produce many harmful effects in the gastro-intestinal tract, which can threaten the well-being of the organisms and their ability to survive.

There are a number of studies showing that glyphosate exposure has produced many negative effects on the intestinal morphology, enzyme and intestinal microbes of various species of aquatic organisms (Cao et al., 2022; Qiu et al., 2020; Bai et al., 2023). Damage to the intestinal structure and function due to glyphosate exposure has also been documented for other species of fish that reside in fresh water (e.g., Channa punctatus ) and damage to these systems impedes the fish's ability to absorb all of the nutrients it needs; therefore, these fish will be more susceptible to disease and will ultimately have impaired growth, behaviour and reproductive success. Glyphosate can also change enzyme systems in the intestinal tract, including glycosidases and peptidases, which are critical enzymes for digestion (Aminov and Golovanova, 2019; Kuzmina et al., 2017). In addition, glyphosate exposure is associated with oxidative stress, inflammation, and apoptosis, and disrupts the integrity of the intestinal barrier in a number of different vertebrate model organisms (Tang et al., 2020; Fadel et al., 2022; Bao et al., 2024).

In addition, glyphosate and its products have been shown to disturb the gut microbiome causing a microbial disturbance that can worsen inflammation and decrease immunity (Mesnage et al., 2022; Krause et al., 2020; Nielsen et al., 2021). Because fish such as Colossoma Macropomum and Carassius auratus have shown microbial and metabolic disturbances (Braz-Mota et al., 2015; Yan et al., 2022). It is anticipated that there will be similar disturbances in bony fish, although they have yet to be well characterised. Additionally, studies of development and across generations indicate that exposure to glyphosate during critical early life stages and/or during perinatal periods has long-lasting effects on intestines structure and function (Del Castillo et al., 2022; Panza et al., 2021; Barnett et al., 2024). These findings emphasize the need to assess both the acute toxicity of glyphosate and the chronic and transgenerational exposure of glyphosate in target aquaculture species such as C. gariepinus. Although the number of ecotoxicology studies has increased, no comprehensive reviews evaluating glyphosate's effects on the intestinal physiology and health of bony fish exist. Most existing studies have generalized across species or focused on other organ systems (e.g., liver, gills) (Bawa et al., 2017; Dey et al., 2016).

Given the critical role of the intestine in fish growth, health and overall aquaculture productivity, understanding the specific effects of glyphosate on this organ system is essential.

EFFECT OF GLYPHOSATE ON INTESTINEOF BONY FISH

The Intestine (Primary Target Organ) exhibits substantial histopathological changes in the intestinal tissues of fish when exposed to glyphosate; these histopathological changes include epithelial degeneration, necrosis, hyperplasia, villus damage to the muscularis atrophy, inflammatory cell infiltration and edema. ther documented histopathological changes to the intestine include structural deformities, including the loss of microvilli and erosion of intestinal mucosa, which also led to impaired nutrient absorption and intestinal dysfunction (Erhunmwunse et al., 2014; Senapati et al., 2009; Bai et al., 2023; Mo et al., 2023; Iannetta et al., 2024). In addition to the effect that glyphosate has on the intestinal structure, it also alters the digestive physiology by inhibiting enzymes associated with digestion and metabolism, such as proteases, amylases and lipases, thereby impairing digestion and metabolism (Senapati et al., 2009; Aminov and Golovanova, 2019; Kuzmina et al., 2017; Salbego et al., 2014). Further, inhibition of intestinal peptidases decreases nutrient assimilation efficiency.

Liver. The liver is another organ that is affected by glyphosate toxicity through biochemical and histopathological modifications (hepatocyte damage, oxidative stress, and metabolism disruption). The liver's biochemistry and histopathology will reflect liver damage if there is an increase in biomarkers of liver function, and there is evidence of degenerating liver tissue (Braz-Mota et al., 2015; Dey et al., 2016; Fadel et al., 2022 ).

The kidney and various organs . Glyphosate exposure has been shown to negatively affect normal kidney function and many other organs in the human body (systemic toxicity) through the induction of numerous effects on their normal function (Braz-Mota et al., 2015; Dey et al., 2016). There is evidence of DNA damage, inhibition of enzymes, and degeneration of tissues in many organs, suggesting potential for damage to more than just the primary target of glyphosate, which is the intestines.

Oxidativestressand cellular/biochemical pathways. xidative stress is the primary mechanism by which glyphosate exerts its toxic effects in humans. Glyphosate-induced oxidative stress has been shown to lead to increased production of R S, lipid peroxidation, disorders of mitochondrial function, apoptosis, inflammation and endoplasmic reticulum stress in many different tissues throughout the human body (Cao et al., 2022; Qiu et al., 2020; Bai et al., 2023; Ding et al., 2021; Peillex and Pelletier, 2020).

Dysfunction of the intestinal barrier. Glyphosate interferes with integrity of the intestinal barrier by downregulating expression of the tight junction proteins Z -1 and claudins and promotes increased intestinal permeability leading to altered gut function (Qiu et al., 2020; Ding et al., 2021).

GUT MICROBIOTA (DYSBIOSIS)

Glyphosate exposure causes changes in the microbial communities of the gut and subsequently causes reduced microbial diversity and dysbiosis. Decreases in microbial diversity and dysbiosis can negatively impact metabolic pathways, the immune response, and general health of the intestines. Probiotic therapy may help restore microbial diversity and reduce toxicity in the gut (Bao et al., 2024; Mesnage et al., 2022; Nielsen et al., 2021; Yan et al., 2022).

ENVIRONMENTAL AND EXPOSUREFACTORS

Environmental contamination from agricultural runoff is also an important source of glyphosate in the aquatic environment. Environmental conditions such as low oxygen levels, hypoxia, and exposure to other stressors increase the oxidative stress, inflammation, and tissue damage associated with glyphosate (Rad et al., 2022; Iannetta et al., 2024).

FUNCTIONAL AND PHYSIOLOGICALEFFECTS

Table 1 : Summarizing the studies

CONCLUSION

In there are potentially significant risks to intestinal health in fish as a result of exposure to glyphosate, including those incurred at sub-lethal concentrations bservational evidence indicates that chronic or repeated exposure to glyphosate damages the intestinal lining (e.g.

broken epithelial layers) and impairs gut function by disrupting digestive enzyme activity and the ability to absorb nutrients, in addition to causing oxidative stress and inflammation. These factors, as well as dysbiosis (i.e., microbial imbalance), may compromise both the structural integrity of the gut and the strength of the immune system, which are critical for the healthy growth of fish. Therefore, any adverse health effects attributable to glyphosate will have substantial implications for both wild fish populations and aquaculture. Future research should continue to explore chronic and developmental effects of exposure, the microbiota specifically, as well as strategies to prevent damage caused by glyphosate through diet-related interventions. Concurrent with these efforts, more stringent regulation of glyphosate and control of its movement into aquatic systems via runoff are required to protect our freshwater ecosystems from contamination by glyphosate.

CONFLICTS OF INTEREST

All authors declare that they have no conflicts of interest.