A review on ecological and physiological studies in bears from a One Health perspective

Abstract

The Hokkaido brown bear is the largest terrestrial mammal in the Hokkaido ecosystems and now inhabits almost all forests in Hokkaido, Japan. These bears have evolved through a unique shift from carnivorous to omnivorous feeding habits, which are of interest to their ecology. However, human-bear conflicts, such as human injury and crop or livestock damage, have become a serious concern, which requires ecological research for its mitigation. The hibernation behavior of bears has unique characteristics that differ from those of other small hibernators, including minimal decrease in body temperature. Interestingly, they show resistance to muscle atrophy and bone loss during prolonged periods of immobility. This review provides an overview of ecological and physiological studies on bears from One Health perspective, focusing on ecology, human-bear conflict, infectious diseases, and hibernating physiology and its application to human health.

INTRODUCTION

The Hokkaido brown bear (Ursus arctos yesoensis) is the largest terrestrial mammal in Japan, and plays an important ecological role as an umbrella species in forest ecosystems. However, in recent years, human–bear conflicts (HBC), including human injuries and agricultural damage, have become a serious social concern [37, 66]. This review focuses on the Hokkaido brown bear, a subspecies of brown bear that occurs only on Hokkaido, the northernmost island of Japan, and summarizes previous research on its ecology, HBC, and infectious diseases. Additionally, this review highlights the characteristics of hibernation physiology in bears and explores the potential contributions of hibernation research to human medicine.

ECOLOGY AND BIOLOGY OF THE HOKKAIDO BROWN BEAR

Physical development

Hokkaido is located at the southern limit of the species’ range, and the Hokkaido brown bear is characterized by a smaller body size compared with brown bear populations in North America and Europe [89]. Moriwaki et al. [49] reported that the maximum weights of males and females were 520 kg and 204 kg, respectively. Sex differences in growth pattern are significant: male bears reach 95% of their asymptotic body mass (approximately 245 kg) by 14.2 years of age, while females reach 95% (approximately 114 kg) by 7.1 years. Due to hibernation during winter, bears show clear seasonal fluctuations in body mass and nutritional status. Body weight typically decreases from the end of hibernation (March–May) to summer, followed by a drastic increase during the autumn hyperphagia period (September–December) [28, 49, 85, 86].

Reproduction

Hokkaido brown bears are seasonal breeders that mate between late April and early July [107], although successful matings after August have also been reported [31, 80]. Female reproduction is characterized by monoestrous, induced ovulation, and delayed implantation [101, 103, 106]. After fertilization, embryonic development is paused, and implantation occurs around early December, coinciding with the onset of hibernation [108]. Cubs are born two months later, between mid-January and early February [104, 105]. Litter sizes range from one to three cubs, with an average of 1.8 cubs/litter [36, 48, 80]—approximately 0.5 fewer cubs/litter than in European or North American populations, which have larger body sizes [44]. The earliest birth occurs at 4 years of age, but usually between 5 and 6 years of age, with an average age of 5.3 years [80]. Males reach sexual maturity at 3–5 years of age in other brown bear populations [110, 112], and the youngest recorded age for successful reproduction in the wild Hokkaido brown bear is 6 years [82]. Male reproductive performance peaks between 10 and 14 years of age, aligning with the period of physical maturity [49, 82]. Females produce cubs once in two to four years, and the mean inter-birth interval is estimated at 2.53 years among litters that survived at least their first year [80]. Compared to other brown bear populations in Europe and North America [89], reproduction in Hokkaido brown bears is characterized by earlier primiparity, smaller litter size, and shorter inter-birth intervals, which compensate for lower litter size and achieve a high reproductive rate (Table 1) [80].

Table 1. Comparisons of female reproductive parameters among different brown bear populations.

Population		AP	LS	IBI	RR	CSR	References
Hokkaido, Japan
	Shiretoko NP (North-eatstern)	5.3	1.59–1.76	2.43–2.53	0.60–0.76	0.60–0.73	[32, 80]
	Oshima Peninsula (South-western)	4#	1.8	2.3–3.0	0.6–0.78	NA	[36]
North America
	Yellowstone NP (USA)	5.7–5.8	1.9–2.2	2.6–3.2	0.64–0.73	0.64–0.85	[73, 89, 92]
	Katmai NP (USA)	7.2	2.06	5.6	0.37	0.34	[74]
Europe
	Sweden	5.2–5.4	2.3–2.4	2.4–2.6	0.92–0.96	0.65–0.96	[63]
	Cantabrian Mountains (Spain)	5.3	1.6–2.3	2.2–3.3	0.7	NA	[61, 111]

AP, Mean age at primiparity (years) (4^#; minimum value); LS, mean litter size; IBI, Inter-birth Intervals (years); RR, reproductive rate (number of young born/year/reproductive adult female); CSR, cub-of-the-year survival rate, NA, no information was available; NP, National Park.

In general, the brown bear mating system is classified as polygamous [89]. Shimozuru et al. [82] reported that in the wild, few physically strong males sometimes monopolize breeding opportunities. However, the females mate with multiple males during a single mating season [7], suggesting promiscuousness. Shimozuru et al. [81] demonstrated that approximately 15% of litters with 2 or more offspring exhibited multiple paternity in brown bear populations on the Shiretoko Peninsula. One possible reason for this promiscuous behavior in females, which have been also reported in other brown bear populations in North America [8] and Europe [5], is that it reduces the risk of infanticide by males by confusing paternity. While male infanticide is a major cause of cub mortality in the European populations [5, 93, 95] and is suggested to be present in Hokkaido as well [21], its frequency in Hokkaido populations remains unknown.

Behavior

Generally, female bears stay near their birthplace (i.e., they are philopatric), whereas males leave their birthplace around sexual maturity. This is called male-biased natal dispersal and plays an important role in maintaining genetic diversity. Although studies on dispersal behavior in Hokkaido brown bears are limited [22, 71, 87, 88], it has been shown that males begin dispersing at around three years of age [87]. Although their dispersal distance (18.3 km on average) is much shorter than that observed in European populations (108.3 km on average) [91], it still contributes to avoid the risk of inbreeding by reducing the occurrence of genetically related males and females in close range [87]. Among 222 mother–father mating pairs, only six litters (2.7%) resulted from mating between fathers and daughters; however, no cases of mating between mothers and sons or between full siblings were observed [81].

The diel activity of Hokkaido brown bears varies by region and season: bears tend to be cathemeral in the southwest [20], diurnal or crepuscular in the eastern [102] and northeast [29, 99], and nocturnal in north Hokkaido [19]. Factors contributing to these differences include the degree of human activity, level of habituation to humans, seasonal changes in feeding behavior, and competitive interactions among bears. For example, inside Shiretoko National Park, where lethal management is rarely implemented, many bears are habituated to humans and exhibit diurnal behavioral patterns, whereas bears outside the park, where hunting and nuisance control exist, tend to be more crepuscular or nocturnal (Fig. 1) [29]. Additionally, females with cubs are more diurnal, likely to reduce the infanticide risk by males [102].

Fig. 1.

Diel activity patterns of brown bears inside and outside the Shiretoko national park (SNP). Red line and open bars areas indicated kernel density estimates and daily observation frequency, respectively. Dark grey shaded area, light grey shaded areas, and white areas indicated night-time, twilight, and day-time, respectively. The figure was reproduced with permission of the Japanese Society of Veterinary Science from Kawamura et al. [29] J Vet Med Sci 84: 1146–1156, 2022.

Feeding habit

The diet of Hokkaido brown bears has been well-studied using methods such as direct examination of fecal or stomach contents [30, 59, 67,68,69, 85] and indirect evaluation using stable isotope analysis of hair and bones [13, 24, 39, 40]. Despite belonging to the order Carnivora, Hokkaido brown bears are omnivores and rely on plant-derived materials for the majority of their diet. From spring to summer, they mainly eat herbaceous plants, especially those belonging to the family Serridae, as well as insects such as ants (Formicidae) and drupes (e.g., Prunus sargentii). During the autumn hyperphagia period, when they gain weight in preparation for hibernation, their main food items include hard mast such as Quercus crispula, along with berries, such as Vitis coignetiae, Sorbus commixta, and Actinidia spp. [85]. Some food resources are available in limited regions, such as salmonids (e.g., pink salmon [Oncorhynchus gorbuscha]) in coastal areas like Shiretoko Peninsula, and Japanese stone pine (Pinus pumila) in the subalpine zone [59, 85]. The consumption of sika deer (Cersus nippon) has increased since 1990’ in parallel with an increase in the deer population [68, 69]. Bears feed on carcasses of deer that have starved to death during winter or left after hunting, as well as fawns born in June [30]. Another change is that bears frequently utilize agricultural crops, especially dent corn in some areas [13, 64]. Additionally, bears sometimes begin to consume new food items that were not previously part of their diet (e.g., cicada nymphs) [100], suggesting high adaptability to environmental changes caused by human activity and climate change.

HUMAN-BROWN BEAR INTERFACE IN HOKKAIDO, JAPAN

Human-bear conflict

HBC, including human injury, intrusion into human residential area, and damage to livestock and agriculture, has become a serious problem over the past two decades, along with the increase in the brown bear population in Hokkaido and growing public concern. The annual number of brown bears killed for management purposes and hunting has increased over the past 30 years, with over 1,800 bears killed in 2023 [17]. However, agricultural damage caused by brown bears continues to increase, rather than decrease, suggesting difficulty in mitigating HBC. These issues are no longer confined to rural areas but have also emerged in urban areas, such as Sapporo city, where so-called “urban bears” have become a concern [66].

Various factors drive toward human settlements. For example, young males are likely to approach human settlements during natal dispersal, presumably because of their low alertness [83, 86]. In addition, females with cubs tend to select habitats near human settlements to avoid the risk of infanticide by males in the European population (a behavior known as human shield hypothesis) [90]. Furthermore, habituation to humans is another important factor that affects these tendencies. Human habituation, defined as a reduced flight response following repeated exposure to human presence and activities [15], commonly occurs in populated areas, including wildlife sanctuaries [60]. While habituated bears provide valuable experience of nature to tourists, they may also increase risk of accidental encounters with people. In Shiretoko National Park, human habituation reduces the fitness of adult females by reducing the survival of their male offspring, owing to an increased likelihood of human-caused mortality [83]. Such human habituation has been occurring in other areas of Hokkaido [37], which may have a negative impact on human safety, as well as on bear survival.

Food availability, especially food shortages during the summer-to-autumn pre-hibernation period, can significantly alter bear behavior and drive them to use agricultural land and approach human settlements [67]. For example, brown bears in Shiretoko National Park rely on a high-calorie diet, including cones of Japanese stone pine, salmonids, and hard masts between late summer and autumn, which drastically improves their nutritional condition in preparation for hibernation (Fig. 2) [85, 86]. However, in years when all or most of these key food items are scarce, many bears are more likely to approach human settlements in search of food and are ultimately killed for management purposes [85]. This “mass occurrence of bears” has happened three times in the Shiretoko Peninsula over the past two decades. In the most recent cases, over 180 bears, equivalent to 40% of minimum population of this peninsula [84], were harvested. Although conditions leading to such mass outbreaks are becoming clearer, effective prevention measures remain limited. This is a significant challenge when considering HBC.

Fig. 2.

Rapid changes in body condition between late August (a) and late October (b) for the same female bear living in the Shiretoko National Park, Hokkaido, Japan. The figure was reproduced with permission of the Institute of Low Temperature Science, Hokkaido University from Shimozuru [75] Low Temp Sci 81: 181–189, 2023.

As noted, one of the factors leading to the increase in HBC is that the brown bear population in Hokkaido has more than doubled over the past 30 years [17]. To mitigate HBC, the Hokkaido government has established a policy to reduce the population by approximately 35% of its 2022 estimate by 2034 [17]. Scientific monitoring of population trends is essential for effective management of bear population. Unfortunately, such monitoring has been implemented only in limited regions in Hokkaido [38, 84, 96]. Understanding population dynamics requires not only the number of bears but also age structure. Recently, robust age estimation has become possible from blood samples by analyzing DNA methylation levels as indicators [54]. This method will contribute to a better understanding of bear ecology and the establishment of bear management plans.

Infectious diseases and zoonotic pathogens

Owing to their large body size and expanded home range [70], brown bears have the potential to carry and transmit numerous bacterial, viral, protozoal, mycotic, helminth, and arthropod-borne pathogens across broad areas. Di Salvo and Chomel [9] reviewed the studies on zoonotic pathogens found in eight bear species worldwide. Reports in Hokkaido brown bears are limited, and most have focused on parasitic infections and arthropod-borne microorganisms. Among parasitic pathogens, Trichinella spp. is of greatest concern to public health as a cause of zoonosis [27, 53]. Other parasites reported in captive and wild Hokkaido brown bears include Dibothriocephalus nihonkaiensis [50, 65], Ancylostoma malayanum [2, 3, 50], Uncinaria sp. [2, 50], Baylisascaris transfuga [2, 50]. Moriyoshi et al. [50] recently confirmed the presence of Strongylida, Capillariidae, and coccidia. They examined 334 fecal samples and reported seasonal, annual, and age-related differences in the prevalence of intestinal parasites, suggesting that both environmental and host factors, including seasonal and/or annual changes in diet, winter hibernation, and host growth, affect parasite infections. Among tick-borne pathogens, Anaplasma sp. has been detected in wild brown bears; however, this Anaplasma species (AP-sd) differs from Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis [51]. In addition, the Hepatozoon spp. and Babesia sp. UR1, Babesia sp. UR2-like and Cytauxzoon sp. UR1 have been reported [34, 52], all of which are considered non-zoonotic. Among the viral pathogens, only one report showed no evidence of SARS-CoV-2 infection in brown bears [33]. Therefore, evidence regarding the presence of zoonotic pathogens that cause serious human illnesses is limited. However, Amblyomma testudinarium, distributed only in the southern part of Japan, is known as a vector of several zoonotic pathogens including severe fever with thrombocytopenia syndrome (SFTS) virus, which has been reported in brown bears captured in eastern Hokkaido [55]. In addition, brown bears opportunistically feed on bird carcasses [54], which indicates a potential risk of highly pathogenic avian influenza (HPAI). All of the above suggest that Hokkaido brown bears could be susceptible to multiple zoonotic pathogens, potentially becoming carriers and transmitting them to other animals, including humans. Further research is required to clarify their roles in pathogen transmission in Hokkaido wildlife.

HIBERNATION PHYSIOLOGY AND IMPLICATIONS FOR HUMAN HEALTH

Due to limited hibernation studies on Hokkaido brown bears, this review includes the biological characteristics of hibernation in three bear species (brown bears, American black bears [U. americanus], and Asiatic black bears [U. thibetanus]) and addresses potential applications of bear hibernation research in human medicine and health promotion. Bears consume large amounts of nutritious food and store body fat during the autumn hyperphagia period (September–November), which enables them to survive the hibernation period (December–April), which is a starvation period. During hibernation, the basal metabolic rate decreases to 25–50% of the active period level [98], and body weight is reduced by 20–40% [94]. Compared to small hibernating mammals, hibernation physiology of bears is characterized by: 1) a smaller drop in body temperature (4–7°C) [16, 79], 2) absence of a typical hibernation cycle consisting of deep torpor and interbout arousal; instead, they remain in a hibernation state almost continuously [98], 3) absence of complete loss of consciousness, as they can respond and move immediately upon receiving external stimuli [16, 35], 4) birth and raising of cubs during hibernation in pregnant females [18], who maintain high body temperature and blood glucose levels for efficient fetal development (Fig. 3) [79]. 5) classification as fat-storing hibernators, as bears survive the hibernation period without eating, drinking, defecating, or urinating, using subcutaneous fat as their main energy source [14, 57]. A comparison of blood biochemical parameters between active and hibernating Japanese black bears (U. thibetanus japonicus) is shown in Table 2. Blood glucose levels are maintained during hibernation, which is thought to be achieved by the upregulation of hepatic gluconeogenesis [76] and suppression of glucose uptake and/or utilization in other organs, including the liver, skeletal muscle, and white adipose tissue [58, 76, 78].

Fig. 3.

Representative changes in body temperature in pregnant (pink line) and non-pregnant (blue line) females during hibernation. The pregnant bear gave birth to cubs on 6 February (dotted line). The body temperature data within 5 days after anesthesia for blood sampling were excluded. The black line indicates changes in ambient temperature in captivity. The figure was reproduced with permission of the Institute of Low Temperature Science, Hokkaido University from Shimozuru [75] Low Temp Sci 81: 181–189, 2023.

Table 2. Comparisons in blood biochemistry values between active (June–July, n=20) and hibernating period (February, n=25) in captive Japanese black bears (Mean ± SD).

	Active period	Hibernation
Glucose (mol/L)	5.0 ± 0.2	4.5 ± 0.2
Triglycerides (mmol/L)	4.1 ± 0.2	8.5 ± 0.5
Total cholesterol (mmol/L)	7.7 ± 0.2	9.4 ± 0.3
Free fatty acids (mmol/L)	0.28 ± 0.06	0.76 ± 0.09
Glycerol (µmol/L)	76.0 ± 11.2	146.6 ± 16.0
Total ketone bodies (µmol/L)	37.6 ± 6.9	664.3 ± 79.6
Urea nitrogen (mmol/L)	3.1 ± 0.2	1.7 ± 0.2
Creatinine (mmol/L)	0.14 ± 0.01	0.21 ± 0.01
Total protein (g/L)	67.0 ± 1.5	79.6 ± 1.2

All values were significantly different among periods. (t-test; P<0.001). The table was reproduced with permission of the Institute of Low Temperature Science, Hokkaido University from Shimozuru [75] Low Temp Sci 81: 181–189, 2023.

Insights into obesity and obesity-related disorders

Bears drastically increase their caloric intake during the autumn hyperphagia period [57], resulting in a rapid increase in body mass over a short period (Fig. 2). Such weight gain is achieved not only by increased dietary intake but also by seasonal changes in endogenous factors, such as increased glucose uptake via upregulation of insulin sensitivity [26] and the activation of lipid synthesis in the liver and white adipose tissue [77, 78]. In general, acute weight gain has serious negative consequences on human health. However, in bears, fasting blood levels of lipids (triglycerides and fatty acids) are the lowest at the peak of the autumn hyperphagia period (early November) [77]. Furthermore, ectopic fat accumulation (such as fatty liver) is absent [25], suggesting that bears serve as an animal model of “healthy obesity.” Notably, hibernation causes insulin resistance in bears [62]. Interestingly, this state is reversible; 10-day period of re-feeding during hibernation reverses insulin resistance and restores glucose metabolism to a state similar to that of the active period [23, 72]. Therefore, bears are expected to be a useful animal model for research on obesity-related human diseases such as type 2 diabetes.

Resistance to muscle atrophy and bone loss

Generally, prolonged immobility causes severe muscle atrophy and bone density loss in humans and other animals. However, in bears, the reduction in muscle strength and skeletal muscle fiber size after a 4–5 month hibernation period is approximately 20–25%, which is limited compared with the predicted human response [12, 45]. This makes hibernating bears an attractive biological model that demonstrates resistance to disuse muscle atrophy. Miyazaki et al. [47] examined alterations in the regulatory systems of protein and energy metabolism in the skeletal muscles of hibernating Asiatic black bears and found that both pathways of muscle protein synthesis and proteolysis were downregulated. This suggests that bears maintain muscle mass and strength by changing protein metabolism to “energy-saving mode.” Interestingly, they also demonstrated that serum from hibernating bears, but not those taken during the active period, increased total protein content in cultured human myotubes [46], suggesting a potential for the development of methods to prevent muscle atrophy and related disorders. Similarly, no trabecular bone loss was observed after a 16–18 weeks disuse (hibernating) period in brown bears [42, 43], suggesting its potential as a translational model of resistance to disuse-induced bone loss and osteoporosis. Although the mechanisms underlying the prevention of bone loss during hibernation are not well understood, the serum concentration of cocaine- and amphetamine-regulated transcripts, a hormone that inhibits bone resorption, is maintained at high levels [41]. Additionally, hibernating bear serum has been shown to hinder osteoclastogenesis in-vitro [56]. These suggest that certain blood components contribute to the maintenance of bone mass.

Possible applications to human health

In addition to the aforementioned traits, bear hibernation has potential applications in promoting human health [10, 109]. For example, bears do not develop atherosclerosis or thrombosis during prolonged immobilization, even though their heart rate is reduced to 10 bpm and blood lipid-related components such as cholesterol are significantly elevated [1]. Recently, Thienel et al. [97] have demonstrated in a mouse model that the hibernation-specific substantial reduction of heat shock protein 47 in platelets contributes to thromboprotection in bears. If this mechanism is further elucidated, it could offer valuable insights into the prevention and treatment of economy class syndrome. Notably, hibernating bears maintain low blood urea nitrogen levels and do not exhibit signs of uremia, despite no urination during hibernation [14]. It has been hypothesized that bears can recycle urea during hibernation; however, this phenomenon has only been addressed in limited reports [4]. Elucidating the mechanism that enables hibernating bears to maintain low urea levels may contribute to the development of treatments for kidney diseases in other animals. While some of these protective mechanisms are known to exist in other small hibernators [6], bears achieve these physiological states without entering extreme hypothermia. This makes them a unique animal model that can be easily applied to human-related studies.

CONCLUSION

To the best of my knowledge, this is the first comprehensive review covering various aspects of bear research, including ecology, HBC, infectious disease, and hibernation physiology, along with its application to human health. Each of these topics is related to the others, and all are important components of the One Health concept [11]. Six of the eight bear species are listed as vulnerable on the International Union for Conservation of Nature Red List (https://www.iucnredlist.org/); thus, further studies on their ecology are needed from a conservation perspective. However, we need to closely monitor population trends, HBC, and wildlife infectious diseases, especially in Japan, where bear urbanization is progressing. Finally, further elucidation of the physiology of hibernating bears has the potential to make innovative contributions to human and veterinary medicine.

CONFLICT OF INTEREST

The author declares no conflicts of interest.